In this research, a solvothermal approach is introduced to synthesize a metal-organic frameworks ... more In this research, a solvothermal approach is introduced to synthesize a metal-organic frameworks (MOFs) nanocomposite (GO/UiO-66-NDC) for the removal of Cr(VI) from water. A comprehensive analysis was performed to understand the physical, chemical, and structural properties of the MOF nanocomposite. The adsorption behavior of Cr(VI) was investigated by changing various parameters, such as pH, dosage, and concentration, to determine isotherms, thermodynamics, and kinetics. The results showed that the nanocomposite had a high tolerance to pH and thermal stability, with a high adsorption capacity of 157.23 mg g −1 for Cr(VI) at pH 3 due to the presence of zirconium oxide clusters. The density functional theory simulations showed that the nanocomposite had ten times more dynamic delocalized surface states, which enhanced the adsorption capacity and agreed with the experimental results. Furthermore, the nanocomposite exhibited better regeneration performance compared to previously reported materials, making it a promising super-adsorbent for removing Cr(VI) from water. The most significant cause of water pollution is chemical pollution, such as heavy metal pollution and various synthetic organic chemicals 1,2. River and stream ecosystem contamination is a growing global concern 3. Due to the rapid expansion of the heavy metal industry in recent years, heavy metal and pesticide pollution has become a severe health and environmental hazard. These contaminants in high concentrations in the ecosystem harm aquatic and terrestrial organisms 4,5. They induce accumulative poisoning, severe damage to the neurological system, lung congestion, liver damage, and oedema in humans. Some pollutants are also carcinogenic 6,7. Chromium (Cr), the first Group 6 element of the periodic table, is the most prevalent heavy metal in groundwater and surface water, and it is frequently derived via chromate manufacturing, metallurgy, metal electroplating, textile dyeing, wood preservation, and tanneries 8,9. The acceptable limit of hexavalent chromium in water for human consumption, according to the WHO, is 50 µg L −1 10. However, Cr(VI) ratios in industrial wastewater range from 5 g L −1 to 270 mg L −1 11. These statistics necessitate the need for water treatment for the removal of chromium. Several methods have been proposed for removing chromium, including chemical precipitation, electrochemical processing, ion exchange, membrane filtration, separation, and adsorption 12,13. Other treatment processes, except adsorption, have substantial downsides, such as expensive pricing, vast volumes of chromium sludge generated, and effective disposal costs 14,15. Adsorption procedures are practical and cost-effective strategies for eliminating chromium ions from wastewater 16. These methods are based on the reliable binding of metal ions to the adsorbent material, which is dependent on analyte-sorbent interactions during the adsorption process 17,18. Metal-organic frameworks (MOFs) are porous inorganic-organic hybrids made up of a regular array of metal ions linked by "linker" molecules (organic) 19,20. Due to their excellent structural homogeneity, homogenous pore structures, adjustable porosity, extensive variety, and flexibility in geometry, chemical functionality, network size, and topology, they provide distinctive structural diversities when compared to other porous materials 21,22. UiO-66 framework (University of Oslo) is a 3D porous material with intriguing features that make it a promising material for adsorption research, including large and uniform pore
The present work deals with the synthesis of acetoxysulfonamide pyrazole derivatives, substituted... more The present work deals with the synthesis of acetoxysulfonamide pyrazole derivatives, substituted 4,5-dihydropyrazole-1-carbothioamide and 4,5-dihydropyrazole-1isonicotinoyl derivatives starting from substituted vanillin chalcones. Acetoxysulfonamide pyrazole derivatives were prepared from the reaction of chalcones with p-sulfamylphenylhydrazine followed by treatment with acetic anhydride. At the same time 4,5-dihydropyrazole-1-carbothioamide and 4,5-dihydropyrazole-1-isonicotinoyl derivatives were prepared from the reaction of chalcones with either thiosemicarbazide or isonicotinic acid hydrazide, respectively. The synthesized compounds were structurally characterized on the basis of IR, 1 H-NMR, 13 C-NMR spectral data and microanalyses. All of the newly isolated compounds were tested for their antimicrobial activities. The antimicrobial screening using the agar well-diffusion method revealed that the chloro derivatives are the most active ones. Moreover, the antioxidant and anti-inflammatory activity of these chloro derivatives are also studied using the DPPH radical scavenging and NO radical scavenging methods, respectively.
Background: Antimicrobial Resistance (AMR) and Tuberculosis (TB) are global concern. According to... more Background: Antimicrobial Resistance (AMR) and Tuberculosis (TB) are global concern. According to the WHO fact sheet on tuberculosis, in 2017, 10 million people fell ill with TB, and 1.6 million including 230,000 children died from the disease. There is a critical need of design and development of novel chemotherapeutic agents to combat the emergence and increasing prevalence of resistant pathogens. In the present study, a new series of 1,3,4-oxadiazoles incorporating benzimidazole and pyridine scaffolds in a single molecular framework has been reported. Methods: The structures of the synthesized derivatives (4a to 4e) were assigned by IR, NMR and mass spectral techniques. The hybrid compounds were evaluated for their antimicrobial, antitubercular and antioxidant activities. In addition, docking simulations were performed to study ligand-protein interactions and to determine the probable binding conformations. Results: Molecule 4a has shown anti-tubular activities with MIC 1.6 μg/ml. As compared to ascorbic acid activities (IC 50 = 62.91 µg/ml), molecule 4e exhibited better antioxidant activities (IC 50 = 24.85 µg/ml). Also, molecule 4e has shown significant antimicrobial activities. Conclusion: The synthesized derivatives from 4a to 4e have exhibited various medicinal activities and could be emerged as lead compounds and further explored as potential therapeutic agents.
A series of some new aryl sulfone derivatives containing benzimidazole moiety were synthesized. T... more A series of some new aryl sulfone derivatives containing benzimidazole moiety were synthesized. The compounds were characterized by means of IR, 1 HNMR and elemental analysis. The compounds were evaluated for antibacterial activity against both gram positive and gram negative organisms with standard benzyl penicillin. Synthesized compounds exhibited significant biological activity.
2-(4-methyl piperazin-1-yl) acetohydrazide was synthesized. The combined practice of IR, 1H NMR, ... more 2-(4-methyl piperazin-1-yl) acetohydrazide was synthesized. The combined practice of IR, 1H NMR, and mass spectrometry established the structure of the synthesized compound. Geometry optimization was performed using DFT at the B3LYP level, employing the basis set 6-31G (d, p). For the optimized structure, surfaces were created to study excited state properties such as electrostatic potential mapped density, highest occupied molecular orbital, lowest unoccupied molecular orbital, ionization energy, and electron affinity. Electric dipole moment, bond length, and angles were computed using the same basis set for the optimized structure. ADMET prediction revealed that the compound possesses the ability to cross the blood-brain barrier and is non-toxic. Further Molecular docking studies with Human Monoamine Oxidase A were carried out to predict the mono-amine inhibitory potential of the compound. The compound revealed better energy scores than the standard. The synthesized compound was evaluated from all aspects concerning essential structural features as well as interaction patterns against selected receptors to be an effective antidepressant. This study would provide an excellent platform to further explore the acetohydrazide derivative toward designing and developing potent and target-specific drug candidates with enhanced binding affinities as an antidepressant.
The emergence of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has imposed a great... more The emergence of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has imposed a greater challenge for the world. Coronavirus has infected over 38.3 million people and caused millions of deaths worldwide. The COVID-19 outbreak has accentuated the need for additional efforts to develop broad-spectrum therapeutics to combat SARS-CoV-2 infection. In the current investigation, an attempt was made to design potential SARS-CoV PLpro inhibitors containing naphthalene and 3,4-dihydro-2H-pyran moieties connected via-NHCO-linker. The ligands obeyed Lipinski's rule and were found to have good drug-likeness and ADMET properties. Docking simulations confirmed strong binding affinity and inhibition potential of the designed ligands against the receptor SARS CoV-2 Papain-like protease (PLpro). LigandL10 incorporating the oxadiazole ring system displayed better binding affinity than the control 5-acetamido-2-methyl-N-[(1R)-1-naphthalen-1-ylethyl]benzamide. Further, the docked complex of LigandL10 was subjected to molecular dynamics (MD) simulation to examine the molecular mechanisms of protein-ligand interactions. The results of the present study are encouraging. Ligand L10 emerged as the most potent ligand in the series and could be considered for further research for the development of potential therapeutics for the treatment of COVID-19.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
A number of new compounds containing the 4-(aminomethyl)benzamide fragment as a linker were desig... more A number of new compounds containing the 4-(aminomethyl)benzamide fragment as a linker were designed and synthesized, and their biological activities were evaluated as potential anticancer agents. The cytotoxicity activity of the designed compounds was studied in two hematological and five solid cell lines in comparison with the reference drugs. Targeted structures against eight receptor tyrosine kinases including EGFR, HER-2, HER-4, IGF1R, InsR, KDR, PDGFRa, and PDGFRb were investigated. The majority of the compounds showed a potent inhibitory activity against the tested kinases. The analogues 11 and 13 with the (trifluoromethyl)benzene ring in the amide or amine moiety of the molecule were proven to be highly potent against EGFR, with 91% and 92% inhibition at 10 nM, respectively. The docking of synthesized target compounds for nine protein kinases contained in the Protein Data Bank (PDB) database was carried out. The molecular modeling results for analogue 10 showed that the use of the 4-(aminomethyl)benzamide as a flexible linker leads to a favorable overall geometry of the molecule, which allows one to bypass the bulk isoleucine residue and provides the necessary binding to the active center of the T315I-mutant Abl (PDB: 3QRJ).
Malaria is a parasitic infection considered a serious global public health problem. Plasmodium fa... more Malaria is a parasitic infection considered a serious global public health problem. Plasmodium falciparum is the causative agent of malaria that presents a greater adaptability by mutation causing resistance to antimalarial drugs. The use of plant material in the treatment of malaria aroused to search natural products as a source of molecules or inspiration for the development of new antimalarial drugs. Dioclea virgata was selected because of its antimalarial potential and for being a plant species present in the semiarid. The objective of this study was to identify flavonoids in D. virgata with potential inhibitory to the promising target, Enoyl-ACP Reductase, present in P. falciparum (PfENR) by virtual screening. Analysis of the extracts of leaves and stems from the D. virgata, by HPLC-DAD allowed to identify the flavonoid luteolin in chloroform extract of leaves, which obtained an affinity energy value of-32.03 Kcal/mol in relation to the enzyme. This negative value indicates that intermolecular interactions were formed easily.
This study investigates the removal of As(V) from aqueous media using water stable UiO-66-NDC/GO ... more This study investigates the removal of As(V) from aqueous media using water stable UiO-66-NDC/GO prepared via the solvothermal procedure. The synthesized material was analyzed by Raman spectroscopy, UV–visible, X-ray powder diffraction (XRD), Transmission electron microscopy (TEM), Fourier Transform Infrared spectroscopy (ATR-FTIR), scanning electron microscopy (SEM), and Brunauer–Emmett–Teller (BET) support its applicability as a super-adsorbent for the adsorption of As(V) ions from aqueous solutions. The effect of various parameters, including initial ion concentration, temperature, adsorbent dose, and pH on the adsorption of As(V) was studied to recognize the optimum adsorption conditions. The qmax obtained for this study using Langmuir isotherms was found at 147.06 mg/g at room temperature. Thermodynamic parameters ΔH°, ΔG°, and ΔS° were also calculated and negative values of ΔG° represent that the As(V) adsorption process occurred exothermically and spontaneously. Meanwhile, th...
Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on ... more Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
A series of some new aryl sulfone derivatives containing benzimidazole moiety were synthesized. T... more A series of some new aryl sulfone derivatives containing benzimidazole moiety were synthesized. The compounds were characterized by means of IR,1HNMR and elemental analysis. The compounds were evaluated..
The emergence of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has imposed a great... more The emergence of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has imposed a greater challenge for the world. Coronavirus has infected over 38.3 million people and caused millions of deaths worldwide. The COVID-19 outbreak has accentuated the need for additional efforts to develop broad-spectrum therapeutics to combat SARS-CoV-2 infection. In the current investigation, an attempt was made to design potential SARS-CoV PLpro inhibitors containing naphthalene and 3,4-dihydro-2H-pyran moieties connected via-NHCO-linker. The ligands obeyed Lipinski's rule and were found to have good drug-likeness and ADMET properties. Docking simulations confirmed strong binding affinity and inhibition potential of the designed ligands against the receptor SARS CoV-2 Papain-like protease (PLpro). LigandL10 incorporating the oxadiazole ring system displayed better binding affinity than the control 5-acetamido-2-methyl-N-[(1R)-1-naphthalen-1-ylethyl]benzamide. Further, the docked complex of LigandL10 was subjected to molecular dynamics (MD) simulation to examine the molecular mechanisms of protein-ligand interactions. The results of the present study are encouraging. Ligand L10 emerged as the most potent ligand in the series and could be considered for further research for the development of potential therapeutics for the treatment of COVID-19.
A tumor may be defined as a mass of cells formed by accumulation of abnormal cells. Under normal ... more A tumor may be defined as a mass of cells formed by accumulation of abnormal cells. Under normal conditions, as the cells in our body undergo senescence, they are replaced by new cells. This normal cell cycle is disrupted in cancer. Unlike normal cells which die after becoming old, tumor cells keep on multiplying regardless of the requirement of the body. As cells continue to get added to the mass, the tumor keeps on proliferating. The genes ErbB3 and erbB2 as heterodimerization partners are involved in various important pathways like growth and proliferation of cancer cells, resistance to chemotherapy as well as boosting metastasis. They are associated with therapeutic resistance having specific targets in various types of cancers including resistance to breast, head, neck, prostate cancers and many more. The study presented in this paper manages the pharmacological investigation and preclinical trials of a designed Receptor; tyrosine-protein kinase erbB-3 interacted to thiohydantoin subordinates fusing different five or six-membered heterocyclic moieties, which can be used as a potential antagonist as shown by in-silico techniques. The ligands thus designed were then analysed using various techniques, such as molecular property prediction, toxicity, solubility and drug-likeness. Its ADMET profile was studied by means of admetSAR. It was observed that all the potential ligands under study had a satisfactory oral bioavailability. They also obeyed Lipinski’s rule. PatchDock was used for analysing the in-silico docking. Priority was given on two salient parameters; Atomic contact energy & Score. Results indicate that all the ligands were having atomic contact energy ranging between – 223.89 and – 327.98 kcal / mol and score between 4690 and 5184. Ligands L07, L13, L03 and L15 have shown improved binding affinity as compared to the benchmark drug. Results stipulate that the designed ligand L03 is a potential antagonist which is exhibiting a stable interaction with the receptor.
International Journal of Peptide Research and Therapeutics, 2018
Prostate cancer is the most prevalent deadly cancer in men worldwide. Androgen receptors are wide... more Prostate cancer is the most prevalent deadly cancer in men worldwide. Androgen receptors are widely recognized for their prognostic and predictive roles in prostate cancer. The current study deals with the pharmacological analysis and preclinical trials of newly designed piperazine linked thiohydantoin derivatives incorporating various five or six-membered heterocyclic moieties using in silico techniques as androgen antagonist. The designed ligands were subjected to molecular properties prediction, solubility, toxicity and drug-likeness. ADMET profile was studied using admetSAR. All the ligands obeyed Lipinski's rule and had good oral bioavailability. Enzlutamide was used as the standard drug. In silico docking, the analysis was carried out using AutoDock 4.2, based on the Lamarckian genetic algorithm principle. The compound was prioritised based on two important parameters like binding energy and inhibition constant. The results showed that all the ligands had binding energy ranging between − 11.1 and − 9.30 kcal/ mol and inhibition constant between 7.25 and 152.11 nM. Ligands L14, L12, L10 and L9 showed better binding affinity compared to the standard drug in docking simulation. The results indicate that the designed ligand, L14 is potential androgen antagonist and showing stability as well after interaction with receptor. The study could lead to the further development of potent androgen antagonist for the treatment of prostate cancer.
A novel synthetic method has been developed with palladium-catalyzed Buchwald-Hartwig-type reacti... more A novel synthetic method has been developed with palladium-catalyzed Buchwald-Hartwig-type reaction for the synthesis of N-tert-butyl-3-{[2-(arylamino)pyrimidin-4-yl]amino} benzenesulfonamide 5 by the treatment of N-tert-butyl-3-[(2-chloropyrimidin-4-yl)amino] benzenesulfonamide 4 with different aromatic amines in the presence of Cs 2 CO 3 and in DMF under microwave conditions. All the eight compounds 5a-h were evaluated for their antibacterial, antifungal, and cytotoxic activities. Among the title compounds, 5c and 5d showed potent activity towards both gram-positive and gram-negative bacteria. Compounds 5c and 5d displayed good antifungal activity, and the compounds 5c, 5d, and 5f exhibited significant cytotoxicity activity.
New series of 1, 3, 4-oxadiazoles incorporating piperazine scaffolds in a single molecular framew... more New series of 1, 3, 4-oxadiazoles incorporating piperazine scaffolds in a single molecular framework has been reported. The structures of the synthesized derivatives were assigned by IR, NMR and mass spectral techniques. The hybrid compounds were evaluated for their antimicrobial, antitubercular and antioxidant activities. The observed MIC values of anti-tubular activities for the molecule 3a, 3b, 3c, 3d and 3e were 6.25, 3.12, 3.12, 1.60 and 50.0 mg/ml respectively. As compared to ascorbic acid (IC 50 ¼ 62.91 mg/ml), molecule 3a exhibited better antioxidant activities (IC 50 ¼ 36.72 mg/ml). Also, all molecules have shown significant antimicrobial activities. In addition, docking simulations were performed to study ligand protein interactions and to determine the probable binding conformations. In drug likeness model study compound 3b possessed maximum drug likeness model score (0.75) similar to the standard drug streptomycin. The compound 3a, 3b and 3c were emerged as potential derivatives in the series and could serve as lead compound for the development of potential therapeutic agents.
In this research, a solvothermal approach is introduced to synthesize a metal-organic frameworks ... more In this research, a solvothermal approach is introduced to synthesize a metal-organic frameworks (MOFs) nanocomposite (GO/UiO-66-NDC) for the removal of Cr(VI) from water. A comprehensive analysis was performed to understand the physical, chemical, and structural properties of the MOF nanocomposite. The adsorption behavior of Cr(VI) was investigated by changing various parameters, such as pH, dosage, and concentration, to determine isotherms, thermodynamics, and kinetics. The results showed that the nanocomposite had a high tolerance to pH and thermal stability, with a high adsorption capacity of 157.23 mg g −1 for Cr(VI) at pH 3 due to the presence of zirconium oxide clusters. The density functional theory simulations showed that the nanocomposite had ten times more dynamic delocalized surface states, which enhanced the adsorption capacity and agreed with the experimental results. Furthermore, the nanocomposite exhibited better regeneration performance compared to previously reported materials, making it a promising super-adsorbent for removing Cr(VI) from water. The most significant cause of water pollution is chemical pollution, such as heavy metal pollution and various synthetic organic chemicals 1,2. River and stream ecosystem contamination is a growing global concern 3. Due to the rapid expansion of the heavy metal industry in recent years, heavy metal and pesticide pollution has become a severe health and environmental hazard. These contaminants in high concentrations in the ecosystem harm aquatic and terrestrial organisms 4,5. They induce accumulative poisoning, severe damage to the neurological system, lung congestion, liver damage, and oedema in humans. Some pollutants are also carcinogenic 6,7. Chromium (Cr), the first Group 6 element of the periodic table, is the most prevalent heavy metal in groundwater and surface water, and it is frequently derived via chromate manufacturing, metallurgy, metal electroplating, textile dyeing, wood preservation, and tanneries 8,9. The acceptable limit of hexavalent chromium in water for human consumption, according to the WHO, is 50 µg L −1 10. However, Cr(VI) ratios in industrial wastewater range from 5 g L −1 to 270 mg L −1 11. These statistics necessitate the need for water treatment for the removal of chromium. Several methods have been proposed for removing chromium, including chemical precipitation, electrochemical processing, ion exchange, membrane filtration, separation, and adsorption 12,13. Other treatment processes, except adsorption, have substantial downsides, such as expensive pricing, vast volumes of chromium sludge generated, and effective disposal costs 14,15. Adsorption procedures are practical and cost-effective strategies for eliminating chromium ions from wastewater 16. These methods are based on the reliable binding of metal ions to the adsorbent material, which is dependent on analyte-sorbent interactions during the adsorption process 17,18. Metal-organic frameworks (MOFs) are porous inorganic-organic hybrids made up of a regular array of metal ions linked by "linker" molecules (organic) 19,20. Due to their excellent structural homogeneity, homogenous pore structures, adjustable porosity, extensive variety, and flexibility in geometry, chemical functionality, network size, and topology, they provide distinctive structural diversities when compared to other porous materials 21,22. UiO-66 framework (University of Oslo) is a 3D porous material with intriguing features that make it a promising material for adsorption research, including large and uniform pore
The present work deals with the synthesis of acetoxysulfonamide pyrazole derivatives, substituted... more The present work deals with the synthesis of acetoxysulfonamide pyrazole derivatives, substituted 4,5-dihydropyrazole-1-carbothioamide and 4,5-dihydropyrazole-1isonicotinoyl derivatives starting from substituted vanillin chalcones. Acetoxysulfonamide pyrazole derivatives were prepared from the reaction of chalcones with p-sulfamylphenylhydrazine followed by treatment with acetic anhydride. At the same time 4,5-dihydropyrazole-1-carbothioamide and 4,5-dihydropyrazole-1-isonicotinoyl derivatives were prepared from the reaction of chalcones with either thiosemicarbazide or isonicotinic acid hydrazide, respectively. The synthesized compounds were structurally characterized on the basis of IR, 1 H-NMR, 13 C-NMR spectral data and microanalyses. All of the newly isolated compounds were tested for their antimicrobial activities. The antimicrobial screening using the agar well-diffusion method revealed that the chloro derivatives are the most active ones. Moreover, the antioxidant and anti-inflammatory activity of these chloro derivatives are also studied using the DPPH radical scavenging and NO radical scavenging methods, respectively.
Background: Antimicrobial Resistance (AMR) and Tuberculosis (TB) are global concern. According to... more Background: Antimicrobial Resistance (AMR) and Tuberculosis (TB) are global concern. According to the WHO fact sheet on tuberculosis, in 2017, 10 million people fell ill with TB, and 1.6 million including 230,000 children died from the disease. There is a critical need of design and development of novel chemotherapeutic agents to combat the emergence and increasing prevalence of resistant pathogens. In the present study, a new series of 1,3,4-oxadiazoles incorporating benzimidazole and pyridine scaffolds in a single molecular framework has been reported. Methods: The structures of the synthesized derivatives (4a to 4e) were assigned by IR, NMR and mass spectral techniques. The hybrid compounds were evaluated for their antimicrobial, antitubercular and antioxidant activities. In addition, docking simulations were performed to study ligand-protein interactions and to determine the probable binding conformations. Results: Molecule 4a has shown anti-tubular activities with MIC 1.6 μg/ml. As compared to ascorbic acid activities (IC 50 = 62.91 µg/ml), molecule 4e exhibited better antioxidant activities (IC 50 = 24.85 µg/ml). Also, molecule 4e has shown significant antimicrobial activities. Conclusion: The synthesized derivatives from 4a to 4e have exhibited various medicinal activities and could be emerged as lead compounds and further explored as potential therapeutic agents.
A series of some new aryl sulfone derivatives containing benzimidazole moiety were synthesized. T... more A series of some new aryl sulfone derivatives containing benzimidazole moiety were synthesized. The compounds were characterized by means of IR, 1 HNMR and elemental analysis. The compounds were evaluated for antibacterial activity against both gram positive and gram negative organisms with standard benzyl penicillin. Synthesized compounds exhibited significant biological activity.
2-(4-methyl piperazin-1-yl) acetohydrazide was synthesized. The combined practice of IR, 1H NMR, ... more 2-(4-methyl piperazin-1-yl) acetohydrazide was synthesized. The combined practice of IR, 1H NMR, and mass spectrometry established the structure of the synthesized compound. Geometry optimization was performed using DFT at the B3LYP level, employing the basis set 6-31G (d, p). For the optimized structure, surfaces were created to study excited state properties such as electrostatic potential mapped density, highest occupied molecular orbital, lowest unoccupied molecular orbital, ionization energy, and electron affinity. Electric dipole moment, bond length, and angles were computed using the same basis set for the optimized structure. ADMET prediction revealed that the compound possesses the ability to cross the blood-brain barrier and is non-toxic. Further Molecular docking studies with Human Monoamine Oxidase A were carried out to predict the mono-amine inhibitory potential of the compound. The compound revealed better energy scores than the standard. The synthesized compound was evaluated from all aspects concerning essential structural features as well as interaction patterns against selected receptors to be an effective antidepressant. This study would provide an excellent platform to further explore the acetohydrazide derivative toward designing and developing potent and target-specific drug candidates with enhanced binding affinities as an antidepressant.
The emergence of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has imposed a great... more The emergence of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has imposed a greater challenge for the world. Coronavirus has infected over 38.3 million people and caused millions of deaths worldwide. The COVID-19 outbreak has accentuated the need for additional efforts to develop broad-spectrum therapeutics to combat SARS-CoV-2 infection. In the current investigation, an attempt was made to design potential SARS-CoV PLpro inhibitors containing naphthalene and 3,4-dihydro-2H-pyran moieties connected via-NHCO-linker. The ligands obeyed Lipinski's rule and were found to have good drug-likeness and ADMET properties. Docking simulations confirmed strong binding affinity and inhibition potential of the designed ligands against the receptor SARS CoV-2 Papain-like protease (PLpro). LigandL10 incorporating the oxadiazole ring system displayed better binding affinity than the control 5-acetamido-2-methyl-N-[(1R)-1-naphthalen-1-ylethyl]benzamide. Further, the docked complex of LigandL10 was subjected to molecular dynamics (MD) simulation to examine the molecular mechanisms of protein-ligand interactions. The results of the present study are encouraging. Ligand L10 emerged as the most potent ligand in the series and could be considered for further research for the development of potential therapeutics for the treatment of COVID-19.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
A number of new compounds containing the 4-(aminomethyl)benzamide fragment as a linker were desig... more A number of new compounds containing the 4-(aminomethyl)benzamide fragment as a linker were designed and synthesized, and their biological activities were evaluated as potential anticancer agents. The cytotoxicity activity of the designed compounds was studied in two hematological and five solid cell lines in comparison with the reference drugs. Targeted structures against eight receptor tyrosine kinases including EGFR, HER-2, HER-4, IGF1R, InsR, KDR, PDGFRa, and PDGFRb were investigated. The majority of the compounds showed a potent inhibitory activity against the tested kinases. The analogues 11 and 13 with the (trifluoromethyl)benzene ring in the amide or amine moiety of the molecule were proven to be highly potent against EGFR, with 91% and 92% inhibition at 10 nM, respectively. The docking of synthesized target compounds for nine protein kinases contained in the Protein Data Bank (PDB) database was carried out. The molecular modeling results for analogue 10 showed that the use of the 4-(aminomethyl)benzamide as a flexible linker leads to a favorable overall geometry of the molecule, which allows one to bypass the bulk isoleucine residue and provides the necessary binding to the active center of the T315I-mutant Abl (PDB: 3QRJ).
Malaria is a parasitic infection considered a serious global public health problem. Plasmodium fa... more Malaria is a parasitic infection considered a serious global public health problem. Plasmodium falciparum is the causative agent of malaria that presents a greater adaptability by mutation causing resistance to antimalarial drugs. The use of plant material in the treatment of malaria aroused to search natural products as a source of molecules or inspiration for the development of new antimalarial drugs. Dioclea virgata was selected because of its antimalarial potential and for being a plant species present in the semiarid. The objective of this study was to identify flavonoids in D. virgata with potential inhibitory to the promising target, Enoyl-ACP Reductase, present in P. falciparum (PfENR) by virtual screening. Analysis of the extracts of leaves and stems from the D. virgata, by HPLC-DAD allowed to identify the flavonoid luteolin in chloroform extract of leaves, which obtained an affinity energy value of-32.03 Kcal/mol in relation to the enzyme. This negative value indicates that intermolecular interactions were formed easily.
This study investigates the removal of As(V) from aqueous media using water stable UiO-66-NDC/GO ... more This study investigates the removal of As(V) from aqueous media using water stable UiO-66-NDC/GO prepared via the solvothermal procedure. The synthesized material was analyzed by Raman spectroscopy, UV–visible, X-ray powder diffraction (XRD), Transmission electron microscopy (TEM), Fourier Transform Infrared spectroscopy (ATR-FTIR), scanning electron microscopy (SEM), and Brunauer–Emmett–Teller (BET) support its applicability as a super-adsorbent for the adsorption of As(V) ions from aqueous solutions. The effect of various parameters, including initial ion concentration, temperature, adsorbent dose, and pH on the adsorption of As(V) was studied to recognize the optimum adsorption conditions. The qmax obtained for this study using Langmuir isotherms was found at 147.06 mg/g at room temperature. Thermodynamic parameters ΔH°, ΔG°, and ΔS° were also calculated and negative values of ΔG° represent that the As(V) adsorption process occurred exothermically and spontaneously. Meanwhile, th...
Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on ... more Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
A series of some new aryl sulfone derivatives containing benzimidazole moiety were synthesized. T... more A series of some new aryl sulfone derivatives containing benzimidazole moiety were synthesized. The compounds were characterized by means of IR,1HNMR and elemental analysis. The compounds were evaluated..
The emergence of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has imposed a great... more The emergence of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has imposed a greater challenge for the world. Coronavirus has infected over 38.3 million people and caused millions of deaths worldwide. The COVID-19 outbreak has accentuated the need for additional efforts to develop broad-spectrum therapeutics to combat SARS-CoV-2 infection. In the current investigation, an attempt was made to design potential SARS-CoV PLpro inhibitors containing naphthalene and 3,4-dihydro-2H-pyran moieties connected via-NHCO-linker. The ligands obeyed Lipinski's rule and were found to have good drug-likeness and ADMET properties. Docking simulations confirmed strong binding affinity and inhibition potential of the designed ligands against the receptor SARS CoV-2 Papain-like protease (PLpro). LigandL10 incorporating the oxadiazole ring system displayed better binding affinity than the control 5-acetamido-2-methyl-N-[(1R)-1-naphthalen-1-ylethyl]benzamide. Further, the docked complex of LigandL10 was subjected to molecular dynamics (MD) simulation to examine the molecular mechanisms of protein-ligand interactions. The results of the present study are encouraging. Ligand L10 emerged as the most potent ligand in the series and could be considered for further research for the development of potential therapeutics for the treatment of COVID-19.
A tumor may be defined as a mass of cells formed by accumulation of abnormal cells. Under normal ... more A tumor may be defined as a mass of cells formed by accumulation of abnormal cells. Under normal conditions, as the cells in our body undergo senescence, they are replaced by new cells. This normal cell cycle is disrupted in cancer. Unlike normal cells which die after becoming old, tumor cells keep on multiplying regardless of the requirement of the body. As cells continue to get added to the mass, the tumor keeps on proliferating. The genes ErbB3 and erbB2 as heterodimerization partners are involved in various important pathways like growth and proliferation of cancer cells, resistance to chemotherapy as well as boosting metastasis. They are associated with therapeutic resistance having specific targets in various types of cancers including resistance to breast, head, neck, prostate cancers and many more. The study presented in this paper manages the pharmacological investigation and preclinical trials of a designed Receptor; tyrosine-protein kinase erbB-3 interacted to thiohydantoin subordinates fusing different five or six-membered heterocyclic moieties, which can be used as a potential antagonist as shown by in-silico techniques. The ligands thus designed were then analysed using various techniques, such as molecular property prediction, toxicity, solubility and drug-likeness. Its ADMET profile was studied by means of admetSAR. It was observed that all the potential ligands under study had a satisfactory oral bioavailability. They also obeyed Lipinski’s rule. PatchDock was used for analysing the in-silico docking. Priority was given on two salient parameters; Atomic contact energy & Score. Results indicate that all the ligands were having atomic contact energy ranging between – 223.89 and – 327.98 kcal / mol and score between 4690 and 5184. Ligands L07, L13, L03 and L15 have shown improved binding affinity as compared to the benchmark drug. Results stipulate that the designed ligand L03 is a potential antagonist which is exhibiting a stable interaction with the receptor.
International Journal of Peptide Research and Therapeutics, 2018
Prostate cancer is the most prevalent deadly cancer in men worldwide. Androgen receptors are wide... more Prostate cancer is the most prevalent deadly cancer in men worldwide. Androgen receptors are widely recognized for their prognostic and predictive roles in prostate cancer. The current study deals with the pharmacological analysis and preclinical trials of newly designed piperazine linked thiohydantoin derivatives incorporating various five or six-membered heterocyclic moieties using in silico techniques as androgen antagonist. The designed ligands were subjected to molecular properties prediction, solubility, toxicity and drug-likeness. ADMET profile was studied using admetSAR. All the ligands obeyed Lipinski's rule and had good oral bioavailability. Enzlutamide was used as the standard drug. In silico docking, the analysis was carried out using AutoDock 4.2, based on the Lamarckian genetic algorithm principle. The compound was prioritised based on two important parameters like binding energy and inhibition constant. The results showed that all the ligands had binding energy ranging between − 11.1 and − 9.30 kcal/ mol and inhibition constant between 7.25 and 152.11 nM. Ligands L14, L12, L10 and L9 showed better binding affinity compared to the standard drug in docking simulation. The results indicate that the designed ligand, L14 is potential androgen antagonist and showing stability as well after interaction with receptor. The study could lead to the further development of potent androgen antagonist for the treatment of prostate cancer.
A novel synthetic method has been developed with palladium-catalyzed Buchwald-Hartwig-type reacti... more A novel synthetic method has been developed with palladium-catalyzed Buchwald-Hartwig-type reaction for the synthesis of N-tert-butyl-3-{[2-(arylamino)pyrimidin-4-yl]amino} benzenesulfonamide 5 by the treatment of N-tert-butyl-3-[(2-chloropyrimidin-4-yl)amino] benzenesulfonamide 4 with different aromatic amines in the presence of Cs 2 CO 3 and in DMF under microwave conditions. All the eight compounds 5a-h were evaluated for their antibacterial, antifungal, and cytotoxic activities. Among the title compounds, 5c and 5d showed potent activity towards both gram-positive and gram-negative bacteria. Compounds 5c and 5d displayed good antifungal activity, and the compounds 5c, 5d, and 5f exhibited significant cytotoxicity activity.
New series of 1, 3, 4-oxadiazoles incorporating piperazine scaffolds in a single molecular framew... more New series of 1, 3, 4-oxadiazoles incorporating piperazine scaffolds in a single molecular framework has been reported. The structures of the synthesized derivatives were assigned by IR, NMR and mass spectral techniques. The hybrid compounds were evaluated for their antimicrobial, antitubercular and antioxidant activities. The observed MIC values of anti-tubular activities for the molecule 3a, 3b, 3c, 3d and 3e were 6.25, 3.12, 3.12, 1.60 and 50.0 mg/ml respectively. As compared to ascorbic acid (IC 50 ¼ 62.91 mg/ml), molecule 3a exhibited better antioxidant activities (IC 50 ¼ 36.72 mg/ml). Also, all molecules have shown significant antimicrobial activities. In addition, docking simulations were performed to study ligand protein interactions and to determine the probable binding conformations. In drug likeness model study compound 3b possessed maximum drug likeness model score (0.75) similar to the standard drug streptomycin. The compound 3a, 3b and 3c were emerged as potential derivatives in the series and could serve as lead compound for the development of potential therapeutic agents.
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Papers by Shipra Bhati