The present work is designed to synthesize 2,5-disubstituted-1,3,4-oxadiazole derivatives 5a-5d a... more The present work is designed to synthesize 2,5-disubstituted-1,3,4-oxadiazole derivatives 5a-5d as snake venom phospholipase A 2 (PLA 2) inhibitors. The snake venom was isolated from Naja oxiana by pressing their glands below eyes to perform anti-PLA 2 activity. The compounds 5a-5d showed good PLA 2 inhibitory potential, especially 5d exhibited excellent activity having IC 50 value 0.002 mM (0.01 > p > 0.001) followed by 5c having IC 50 value 0.003 mM (0.01 > p > 0.001). Compounds 5a and 5b have IC 50 values 0.027 mM (p < 0.001) and 0.014 mM (p < 0.001) respectively. The docking results showed that all compounds have binding interactions with amino acid residues in active binding site. They have good binding affinities, particularly 5d has binding energy-6.8 kcal/mol compared to other analogues. On the basis of dry and wet lab results, it may proposed that 5d may act as a potent inhibitor of PLA 2 in N. oxiana venom.
Recent recognition about snake bite envenomation on June, 2017 as neglected tropical disease unde... more Recent recognition about snake bite envenomation on June, 2017 as neglected tropical disease under category-A by World Health Organization advocated again its undeniable importance. Present circumstances reasoned to work on a neglected subspecies of Naja naja, i.e., Naja naja karachiensis (N. n. karachensis) has been documented for frequent deaths in Pakistan. In this study median lethal toxic dose (LD) was determined intraperitoneally in Swiss albino mice and was found to be 2.0µg/g (2.0mg/kg) equal in potency to Naja pallida (red spitting African cobra). Total protein contents (188±0.011µg / 200µg of dry weight) were high enough (94%) to represent an arsenal of proteins. Furthermore, Tc was labeled 99.9% with venom and didn't find to alter hemolytic activity of venom in dose dependent manner at 125μg/ml (p>0.5), 250 μg/ml (p>0.1) and 500 μg/ml (p>0.1) when compared with its crude form. Present work will pave the way for proteomics study in effective production of anti...
Medicinal plants of Pakistan are known for their curative properties against snake bite as rural ... more Medicinal plants of Pakistan are known for their curative properties against snake bite as rural people have been using natural herbs for such injuries for hundreds to thousands of years. People of rural areas of Pakistan are prone to snakebite, and on the whole death due to snakebite has been increasing worldwide. The objective of this study was to test the neutralizing potential of 17 Pakistani medicinal plant extracts against phospholipase A2 activity in Echis carinatus venom. Plant material was extracted by simple maceration and fractionation of active plant extracts. Venom was collected by manual massage of the venom glands. The PLA2 enzymatic assay was performed to map out the venomous activity of Echis carinatus envenomation. Snake venom released fatty acids at different concentrations (0.1-5 mg/ml) of venom in a dose-dependent manner. Reduction of pH by 01 correlated with 133 μmol of fatty acids released at 5mg/ml of venom. All plants extract inhibited PLA2 activity, however...
Background Dryopteris ramosa has numerous potentials uses in the treatment of different maladies ... more Background Dryopteris ramosa has numerous potentials uses in the treatment of different maladies as old traditional medication. The fronds of D. ramose are edible and orally administered for producing antibiotic effect. They are also used as astringent and febrifuge, and as a pesticide. Methods Extraction of fronds of D. ramosa using solvents of increasing polarity, namely, ethyl acetate, methanol and water were tested for phytochemical (qualitative tests, GC-MS), antimicrobial (well method), antioxidant (DPPH), antifungal (tube dilution), cytotoxic activity (brine shrimps lethality assay) and LOX and COX inhibitory activities were performed using standard methods. Results The phytochemical analysis of the crude methanolic extract revealed that the fronds are rich in flavonoids, alkaloids, saponins, tannins, glycosides and triterpenoids. The total flavonoid content of the ethyl acetate fraction was 46.28 μg QE/mg extract. The GC-MS analysis revealed nine major compounds that constit...
Phospholipases A2 (PLA2) are the most lethal and noxious component of Naja naja karachiensis veno... more Phospholipases A2 (PLA2) are the most lethal and noxious component of Naja naja karachiensis venom. They are engaged to induce severe toxicities after their penetration in victims. Present study was designed to highlight hydrolytic actions of PLA. in an egg yolk mixture and to encounter their deleterious effects via medicinal plants of Pakistan. PLA2 were found to produce free fatty acids in a dose dependent manner. Venom at concentration of 0.1 mg was found to liberate 26.6 pmoles of fatty acids with a decline in pH1 of 0.2 owing to the presence of PLA2 (133 Unit/mg). When quantity of venom was increased up to 8 mg, it caused to release 133 pmoles of free fatty acids with a decrease in 1.0 pH due to abundance in PLA, (665 Unit/mg). The rest of other doses of venom (0.3-4.0 mg) was found to liberate fatty acids between these two upper and lower limits. Twenty eight medicinal plants (0.1-0.6 mg) were tried to abort PLA, hydrolytic action, however, all were found useful (50-100%) agai...
The aim of this study was to evaluate the effect of venom from Naja naja karachiensis on platelet... more The aim of this study was to evaluate the effect of venom from Naja naja karachiensis on platelet-poor plasma, activated partial thromboplastin time (aPTT), prothrombin time (PT) / international normalized ratio (INR), thrombin time (TT) and to evaluate its effect on clotting time upon storage of plasma for a specific time period with possible mechanism responsible for that. Prolongation of PT / INR, aPTT and TT was observed when different concentrations of venom were introduced due to degeneration of fibrinogen. Preservation of plasma for three months further prolong clotting time for coagulation tests, however, difference of PT and TT results were not very prominent as compared to aPTT. Minute concentrations of cobra venom and short as well as long storage of platelet-poor plasma badly affects the INR ratio.
Malaria, dengue and chikungunya are the most rampant mosquito-borne infections predominantly in P... more Malaria, dengue and chikungunya are the most rampant mosquito-borne infections predominantly in Pakistan. They pose a serious threat and cause a havoc for the victims owing to the life threatening signs and symptoms marked with elevated morbidity and mortality rate. It seems hard to discriminate due to common indications, consequently, deserves appropriate diagnosis prior elevated toll of death. Present article encompasses depth insights about their prevalence, diagnosis and clinical manifestation if erupt in the pandemic. However, host-vector-host cycle is the root cause of transmission and diverse mosquito species confer dissimilar infections. Indeed these infections are seasonal but other factors like flood, open irrigation channels, immense agricultural land, rich fauna and water reservoirs can't be overlooked. Dire need was felt to acknowledge and aware the public about local transmission, vector control, entomologic, research resources, diagnosis and advancement in healthc...
Aim of this study was to synthesize new inhibitors on the basis of active site of aspartic protea... more Aim of this study was to synthesize new inhibitors on the basis of active site of aspartic protease enzyme and to evaluate their intended biological activity. A3D model of an enzyme was generated via homology modeling and series of novel amide ligands were synthesized by using a short high yield process, subsequently, analyzed in-silico and in-vitro anti-leishmanial activities. Characterization and identification was accomplished via NMR (H1& C13), infrared and mass spectroscopic techniques. Among all compound (4) was found to show significant activity (IC50 58±0.01) against Leishmania major (L. major) species. Furthermore, docking studies confirmed the inhibition of a targeted enzyme that supported the interaction of potent compound (4) with key residues (aspartic protease) via hydrogen bonds. Present study conferred about novel compound (4) as a promising compound to antagonize L. major activities in future.
Plants have been extensively used as a remedy for the treatment of snake bites. The aim of this s... more Plants have been extensively used as a remedy for the treatment of snake bites. The aim of this study was to determine the antivenom potentials of methanolic extract from the aerial parts (leaves and twigs) of Fagonia cretica L. on a haemorrhage induced by venom from Naja naja karachiensis. The haemorrhagic response of venom was dose dependent from 0.1 to 4.0 µg per 1.5 µL phosphate buffer saline (PBS) on vitelline veins of fertilised hens’ eggs in their shells. The extract effectively eliminated and neutralised, in a dose-dependent manner, the haemorrhagic activity of snake venom. The minimum effective neutralising dose of F. cretica extract was found to be 15 µg per 1.5 µL PBS. The extract possesses potentials as haemorrhagic inhibitor against snake venom compared to the standard antiserum and various plants reported in the literature. This study also provides a scientific base for the use of F. cretica in traditional medicine for the treatment of snake bite.
Naja naja karachiensis have been responsible for plentiful deaths in Pakistan. To investigate bio... more Naja naja karachiensis have been responsible for plentiful deaths in Pakistan. To investigate bio distribution and blood kinetics, venom was labeled with the radiotracer (technetium-99m) by following the method of direct labeling technique. Its maximum labeling percentage was 97.7% (pH 6, 100 µg stannous chloride dihydrate) which was higher than some other reported venom. Radio labeled venom was stable for more than 4 hours both in vivo (96%) and in vitro (serum 94.1%, saline 94.3%) experimentations. Intravenous doses of venom (250 µg, 0.5 mCi) were found to be evenly distributed (having R/L ratio=1.0) in all parts of sacrificed rabbits. Kidneys (53.75% activity/g) and urinary bladder (23.70% activity/g) were found with the copious quantity of injected dose of venom. Rest of all other organs was found with subsequent remaining dose of venom. Among them, lungs (14.2% activity/g), liver (4.32% activity/g), bones (1.38% activity/g), heart (0.8% activity/g), blood (0.56% activity/g), sk...
Echis carinatus is one of the highly venomous snakes of Pakistan that is responsible for numerous... more Echis carinatus is one of the highly venomous snakes of Pakistan that is responsible for numerous cases of envenomation and deaths. In Pakistan, medicinal plants are commonly used traditionally for snakebite treatment because of their low cost and easy availability in comparison with antivenom. The current research is aimed at evaluating the inhibitory activity of Pakistani medicinal plants against acetylcholinesterase and 5′-nucleotidases present in Echis carinatus venom. Acetylcholinesterase and 5′-nucleotidase enzymatic assays were performed at different venom concentrations to check the activity of these enzymes. Methanolic extracts from different parts of plants were used for in vitro determination of their inhibitory activity against 5′-nucleotidases in snake venom. Active methanolic extracts were subsequently fractioned using different solvents, and these fractions were also assessed for their anti-5′-nucleotidase activity. Results of this study exhibited that Eugenia jambola...
Carbamazepine (CBZ) is an antiepileptic drug having low bioavailability due to its hydrophobic na... more Carbamazepine (CBZ) is an antiepileptic drug having low bioavailability due to its hydrophobic nature. In the current study, efforts are made to investigate the effect of dicarboxylic acid coformer spacer groups (aliphatic chain length) on physicochemical properties, relative humidity (RH) stability, and oral bioavailability of CBZ cocrystals. Slurry crystallization technique was employed for the preparation of CBZ cocrystals with the following coformers: adipic (AA), glutaric (GA), succinic (SA), and malonic acid (MA). Powder X-ray diffractometry and Fourier-transform infrared spectroscopy confirmed cocrystal preparation. Physicochemical properties, RH stability, and oral bioavailability of cocrystals were investigated. Among the prepared cocrystals, CBZ-GA showed maximum solubility as well as improved dissolution profile (CBZ-GA > CBZ-MA > CBZ-AA > pure CBZ > CBZ-SA) in ethanol. Maximum RH stability was shown by CBZ-AA, CBZ-SA, and CBZ-MA. In vivo studies confirmed boo...
This study was conducted to assess the compatibility of aspirin with selective amino acids by stu... more This study was conducted to assess the compatibility of aspirin with selective amino acids by studying the effect of amino acids on the solubility of aspirin, so that the attention could be paid towards the use of proteinous foods along with aspirin. Two different types of dissolution media, i.e., 0.5% solution of each amino acid and 100 mL of distilled water (100 mL each), were prepared. Then, 1 g of aspirin was added in both media and shaked gently. Ten milliliters of sample was withdrawn at different time intervals, i.e., 10, 20, 30, 40, 50 and 60 min and analyzed spectrophotometrically at 265 nm. It is evident from results that the absorbance of aspirin increased with the addition of amino acids and this increase was significant (p < 0.05). Absorbance after adding amino acid like glycine, tyrosine, glutamic acid, tartaric acid and aspartic acid was observed to be 2.98, 2.96, 2.92, 3.23 and 3.28, respectively, as compared to that of aspirin alone. The increase in absorbance of...
The development and optimization of controlled release lipospheres (LS) from safe biocompatible b... more The development and optimization of controlled release lipospheres (LS) from safe biocompatible behenic acid (BA) was performed for not only enhancing patient’s compliance against highly prevailed chronic diabetes but also to vanquish the insufficiencies of traditional methods of drug delivery. The Box-Bhenken design (BBD) was utilized to statistically investigate the impact of formulation variables on percentage yield ( Y 1 ), entrapment efficiency ( Y 2 ), and SG-release ( Y 3 ) from saxagliptin- (SG-) loaded LS, and the chosen optimized LS were subjected to a comparative in vivo pharmacokinetic analysis against commercially available SG brand. The compatibility analysis performed by DSC and FTIR established a complete lack of interaction of formulation components with SG, while p-XRD suggested a mild transformation of crystalline drug to its amorphous form during encapsulation process. The spherical, free flowing smooth surface LS having zeta potential of -32 mV and size range of...
A series of halo-substituted mixed ester/amide-based analogues 4a-l have been prepared as jack be... more A series of halo-substituted mixed ester/amide-based analogues 4a-l have been prepared as jack bean urease inhibitor, which showed good to excellent inhibition of enzyme activity. The role of halo-substituted benzoyl moieties and alkyl substituted anilines in urease inhibitory kinetics was also investigated. The alkyl-substituted anilines 1a–b reacted with chloroacetyl chloride to afford intermediates 2a-b, which were then reacted with different halo-substituted benzoic acids 3a–f to prepare the title compounds 4a-l. The chemical structures of final products 4a-l were ascertained by FTIR, 1H NMR, 13C NMR, and mass spectra. The compound 4b showed remarkable activity with IC50 1.6 ± 0.2 nM, better than the standard thiourea having IC50 472.1 ± 135.1 nM. The 2-chloro-substituted phenyl ring on one side of compound 4b and 4-isopropyl-substituted benzene on the other side play an essential role in inhibition of urease activity. Lineweaver–Burk plots (kinetics study) indicated about 4b ...
Lectins are the oligomeric sugar-specific glycoprotein of nonimmune origin, are involved in the m... more Lectins are the oligomeric sugar-specific glycoprotein of nonimmune origin, are involved in the multiple biological recognition process, and have the capacity to perform a wide variety of physiological functions including antifungal, antiviral, antitumor, and cell agglutination. The main objective of the current study was to prepare lectin protein-loaded chitosan-TPP nanoparticles via ionic gelation methods with different CS/TPP ratios and to investigate anticancer potential against HepG2 cells. The best ratio showed the mean particle size ( 298.10 ± 1.9 nm, 21.05 ± 0.95 mv) with optimal encapsulation efficiencies of 52.435 ± 0.09 % . The cytotoxicity was evaluated against HepG2 cells, and IC50 values obtained were 265 μg/ml for lectin protein and 105 μg/ml for lectin-loaded chitosan-TPP nanoparticles, respectively. The mRNA expression of proliferation markers like GPC3 was significantly decreased in hepatocellular carcinoma cells (HepG2) during lectin protein-loaded chitosan-TPP ...
The present work is designed to synthesize 2,5-disubstituted-1,3,4-oxadiazole derivatives 5a-5d a... more The present work is designed to synthesize 2,5-disubstituted-1,3,4-oxadiazole derivatives 5a-5d as snake venom phospholipase A 2 (PLA 2) inhibitors. The snake venom was isolated from Naja oxiana by pressing their glands below eyes to perform anti-PLA 2 activity. The compounds 5a-5d showed good PLA 2 inhibitory potential, especially 5d exhibited excellent activity having IC 50 value 0.002 mM (0.01 > p > 0.001) followed by 5c having IC 50 value 0.003 mM (0.01 > p > 0.001). Compounds 5a and 5b have IC 50 values 0.027 mM (p < 0.001) and 0.014 mM (p < 0.001) respectively. The docking results showed that all compounds have binding interactions with amino acid residues in active binding site. They have good binding affinities, particularly 5d has binding energy-6.8 kcal/mol compared to other analogues. On the basis of dry and wet lab results, it may proposed that 5d may act as a potent inhibitor of PLA 2 in N. oxiana venom.
Recent recognition about snake bite envenomation on June, 2017 as neglected tropical disease unde... more Recent recognition about snake bite envenomation on June, 2017 as neglected tropical disease under category-A by World Health Organization advocated again its undeniable importance. Present circumstances reasoned to work on a neglected subspecies of Naja naja, i.e., Naja naja karachiensis (N. n. karachensis) has been documented for frequent deaths in Pakistan. In this study median lethal toxic dose (LD) was determined intraperitoneally in Swiss albino mice and was found to be 2.0µg/g (2.0mg/kg) equal in potency to Naja pallida (red spitting African cobra). Total protein contents (188±0.011µg / 200µg of dry weight) were high enough (94%) to represent an arsenal of proteins. Furthermore, Tc was labeled 99.9% with venom and didn't find to alter hemolytic activity of venom in dose dependent manner at 125μg/ml (p>0.5), 250 μg/ml (p>0.1) and 500 μg/ml (p>0.1) when compared with its crude form. Present work will pave the way for proteomics study in effective production of anti...
Medicinal plants of Pakistan are known for their curative properties against snake bite as rural ... more Medicinal plants of Pakistan are known for their curative properties against snake bite as rural people have been using natural herbs for such injuries for hundreds to thousands of years. People of rural areas of Pakistan are prone to snakebite, and on the whole death due to snakebite has been increasing worldwide. The objective of this study was to test the neutralizing potential of 17 Pakistani medicinal plant extracts against phospholipase A2 activity in Echis carinatus venom. Plant material was extracted by simple maceration and fractionation of active plant extracts. Venom was collected by manual massage of the venom glands. The PLA2 enzymatic assay was performed to map out the venomous activity of Echis carinatus envenomation. Snake venom released fatty acids at different concentrations (0.1-5 mg/ml) of venom in a dose-dependent manner. Reduction of pH by 01 correlated with 133 μmol of fatty acids released at 5mg/ml of venom. All plants extract inhibited PLA2 activity, however...
Background Dryopteris ramosa has numerous potentials uses in the treatment of different maladies ... more Background Dryopteris ramosa has numerous potentials uses in the treatment of different maladies as old traditional medication. The fronds of D. ramose are edible and orally administered for producing antibiotic effect. They are also used as astringent and febrifuge, and as a pesticide. Methods Extraction of fronds of D. ramosa using solvents of increasing polarity, namely, ethyl acetate, methanol and water were tested for phytochemical (qualitative tests, GC-MS), antimicrobial (well method), antioxidant (DPPH), antifungal (tube dilution), cytotoxic activity (brine shrimps lethality assay) and LOX and COX inhibitory activities were performed using standard methods. Results The phytochemical analysis of the crude methanolic extract revealed that the fronds are rich in flavonoids, alkaloids, saponins, tannins, glycosides and triterpenoids. The total flavonoid content of the ethyl acetate fraction was 46.28 μg QE/mg extract. The GC-MS analysis revealed nine major compounds that constit...
Phospholipases A2 (PLA2) are the most lethal and noxious component of Naja naja karachiensis veno... more Phospholipases A2 (PLA2) are the most lethal and noxious component of Naja naja karachiensis venom. They are engaged to induce severe toxicities after their penetration in victims. Present study was designed to highlight hydrolytic actions of PLA. in an egg yolk mixture and to encounter their deleterious effects via medicinal plants of Pakistan. PLA2 were found to produce free fatty acids in a dose dependent manner. Venom at concentration of 0.1 mg was found to liberate 26.6 pmoles of fatty acids with a decline in pH1 of 0.2 owing to the presence of PLA2 (133 Unit/mg). When quantity of venom was increased up to 8 mg, it caused to release 133 pmoles of free fatty acids with a decrease in 1.0 pH due to abundance in PLA, (665 Unit/mg). The rest of other doses of venom (0.3-4.0 mg) was found to liberate fatty acids between these two upper and lower limits. Twenty eight medicinal plants (0.1-0.6 mg) were tried to abort PLA, hydrolytic action, however, all were found useful (50-100%) agai...
The aim of this study was to evaluate the effect of venom from Naja naja karachiensis on platelet... more The aim of this study was to evaluate the effect of venom from Naja naja karachiensis on platelet-poor plasma, activated partial thromboplastin time (aPTT), prothrombin time (PT) / international normalized ratio (INR), thrombin time (TT) and to evaluate its effect on clotting time upon storage of plasma for a specific time period with possible mechanism responsible for that. Prolongation of PT / INR, aPTT and TT was observed when different concentrations of venom were introduced due to degeneration of fibrinogen. Preservation of plasma for three months further prolong clotting time for coagulation tests, however, difference of PT and TT results were not very prominent as compared to aPTT. Minute concentrations of cobra venom and short as well as long storage of platelet-poor plasma badly affects the INR ratio.
Malaria, dengue and chikungunya are the most rampant mosquito-borne infections predominantly in P... more Malaria, dengue and chikungunya are the most rampant mosquito-borne infections predominantly in Pakistan. They pose a serious threat and cause a havoc for the victims owing to the life threatening signs and symptoms marked with elevated morbidity and mortality rate. It seems hard to discriminate due to common indications, consequently, deserves appropriate diagnosis prior elevated toll of death. Present article encompasses depth insights about their prevalence, diagnosis and clinical manifestation if erupt in the pandemic. However, host-vector-host cycle is the root cause of transmission and diverse mosquito species confer dissimilar infections. Indeed these infections are seasonal but other factors like flood, open irrigation channels, immense agricultural land, rich fauna and water reservoirs can't be overlooked. Dire need was felt to acknowledge and aware the public about local transmission, vector control, entomologic, research resources, diagnosis and advancement in healthc...
Aim of this study was to synthesize new inhibitors on the basis of active site of aspartic protea... more Aim of this study was to synthesize new inhibitors on the basis of active site of aspartic protease enzyme and to evaluate their intended biological activity. A3D model of an enzyme was generated via homology modeling and series of novel amide ligands were synthesized by using a short high yield process, subsequently, analyzed in-silico and in-vitro anti-leishmanial activities. Characterization and identification was accomplished via NMR (H1& C13), infrared and mass spectroscopic techniques. Among all compound (4) was found to show significant activity (IC50 58±0.01) against Leishmania major (L. major) species. Furthermore, docking studies confirmed the inhibition of a targeted enzyme that supported the interaction of potent compound (4) with key residues (aspartic protease) via hydrogen bonds. Present study conferred about novel compound (4) as a promising compound to antagonize L. major activities in future.
Plants have been extensively used as a remedy for the treatment of snake bites. The aim of this s... more Plants have been extensively used as a remedy for the treatment of snake bites. The aim of this study was to determine the antivenom potentials of methanolic extract from the aerial parts (leaves and twigs) of Fagonia cretica L. on a haemorrhage induced by venom from Naja naja karachiensis. The haemorrhagic response of venom was dose dependent from 0.1 to 4.0 µg per 1.5 µL phosphate buffer saline (PBS) on vitelline veins of fertilised hens’ eggs in their shells. The extract effectively eliminated and neutralised, in a dose-dependent manner, the haemorrhagic activity of snake venom. The minimum effective neutralising dose of F. cretica extract was found to be 15 µg per 1.5 µL PBS. The extract possesses potentials as haemorrhagic inhibitor against snake venom compared to the standard antiserum and various plants reported in the literature. This study also provides a scientific base for the use of F. cretica in traditional medicine for the treatment of snake bite.
Naja naja karachiensis have been responsible for plentiful deaths in Pakistan. To investigate bio... more Naja naja karachiensis have been responsible for plentiful deaths in Pakistan. To investigate bio distribution and blood kinetics, venom was labeled with the radiotracer (technetium-99m) by following the method of direct labeling technique. Its maximum labeling percentage was 97.7% (pH 6, 100 µg stannous chloride dihydrate) which was higher than some other reported venom. Radio labeled venom was stable for more than 4 hours both in vivo (96%) and in vitro (serum 94.1%, saline 94.3%) experimentations. Intravenous doses of venom (250 µg, 0.5 mCi) were found to be evenly distributed (having R/L ratio=1.0) in all parts of sacrificed rabbits. Kidneys (53.75% activity/g) and urinary bladder (23.70% activity/g) were found with the copious quantity of injected dose of venom. Rest of all other organs was found with subsequent remaining dose of venom. Among them, lungs (14.2% activity/g), liver (4.32% activity/g), bones (1.38% activity/g), heart (0.8% activity/g), blood (0.56% activity/g), sk...
Echis carinatus is one of the highly venomous snakes of Pakistan that is responsible for numerous... more Echis carinatus is one of the highly venomous snakes of Pakistan that is responsible for numerous cases of envenomation and deaths. In Pakistan, medicinal plants are commonly used traditionally for snakebite treatment because of their low cost and easy availability in comparison with antivenom. The current research is aimed at evaluating the inhibitory activity of Pakistani medicinal plants against acetylcholinesterase and 5′-nucleotidases present in Echis carinatus venom. Acetylcholinesterase and 5′-nucleotidase enzymatic assays were performed at different venom concentrations to check the activity of these enzymes. Methanolic extracts from different parts of plants were used for in vitro determination of their inhibitory activity against 5′-nucleotidases in snake venom. Active methanolic extracts were subsequently fractioned using different solvents, and these fractions were also assessed for their anti-5′-nucleotidase activity. Results of this study exhibited that Eugenia jambola...
Carbamazepine (CBZ) is an antiepileptic drug having low bioavailability due to its hydrophobic na... more Carbamazepine (CBZ) is an antiepileptic drug having low bioavailability due to its hydrophobic nature. In the current study, efforts are made to investigate the effect of dicarboxylic acid coformer spacer groups (aliphatic chain length) on physicochemical properties, relative humidity (RH) stability, and oral bioavailability of CBZ cocrystals. Slurry crystallization technique was employed for the preparation of CBZ cocrystals with the following coformers: adipic (AA), glutaric (GA), succinic (SA), and malonic acid (MA). Powder X-ray diffractometry and Fourier-transform infrared spectroscopy confirmed cocrystal preparation. Physicochemical properties, RH stability, and oral bioavailability of cocrystals were investigated. Among the prepared cocrystals, CBZ-GA showed maximum solubility as well as improved dissolution profile (CBZ-GA > CBZ-MA > CBZ-AA > pure CBZ > CBZ-SA) in ethanol. Maximum RH stability was shown by CBZ-AA, CBZ-SA, and CBZ-MA. In vivo studies confirmed boo...
This study was conducted to assess the compatibility of aspirin with selective amino acids by stu... more This study was conducted to assess the compatibility of aspirin with selective amino acids by studying the effect of amino acids on the solubility of aspirin, so that the attention could be paid towards the use of proteinous foods along with aspirin. Two different types of dissolution media, i.e., 0.5% solution of each amino acid and 100 mL of distilled water (100 mL each), were prepared. Then, 1 g of aspirin was added in both media and shaked gently. Ten milliliters of sample was withdrawn at different time intervals, i.e., 10, 20, 30, 40, 50 and 60 min and analyzed spectrophotometrically at 265 nm. It is evident from results that the absorbance of aspirin increased with the addition of amino acids and this increase was significant (p < 0.05). Absorbance after adding amino acid like glycine, tyrosine, glutamic acid, tartaric acid and aspartic acid was observed to be 2.98, 2.96, 2.92, 3.23 and 3.28, respectively, as compared to that of aspirin alone. The increase in absorbance of...
The development and optimization of controlled release lipospheres (LS) from safe biocompatible b... more The development and optimization of controlled release lipospheres (LS) from safe biocompatible behenic acid (BA) was performed for not only enhancing patient’s compliance against highly prevailed chronic diabetes but also to vanquish the insufficiencies of traditional methods of drug delivery. The Box-Bhenken design (BBD) was utilized to statistically investigate the impact of formulation variables on percentage yield ( Y 1 ), entrapment efficiency ( Y 2 ), and SG-release ( Y 3 ) from saxagliptin- (SG-) loaded LS, and the chosen optimized LS were subjected to a comparative in vivo pharmacokinetic analysis against commercially available SG brand. The compatibility analysis performed by DSC and FTIR established a complete lack of interaction of formulation components with SG, while p-XRD suggested a mild transformation of crystalline drug to its amorphous form during encapsulation process. The spherical, free flowing smooth surface LS having zeta potential of -32 mV and size range of...
A series of halo-substituted mixed ester/amide-based analogues 4a-l have been prepared as jack be... more A series of halo-substituted mixed ester/amide-based analogues 4a-l have been prepared as jack bean urease inhibitor, which showed good to excellent inhibition of enzyme activity. The role of halo-substituted benzoyl moieties and alkyl substituted anilines in urease inhibitory kinetics was also investigated. The alkyl-substituted anilines 1a–b reacted with chloroacetyl chloride to afford intermediates 2a-b, which were then reacted with different halo-substituted benzoic acids 3a–f to prepare the title compounds 4a-l. The chemical structures of final products 4a-l were ascertained by FTIR, 1H NMR, 13C NMR, and mass spectra. The compound 4b showed remarkable activity with IC50 1.6 ± 0.2 nM, better than the standard thiourea having IC50 472.1 ± 135.1 nM. The 2-chloro-substituted phenyl ring on one side of compound 4b and 4-isopropyl-substituted benzene on the other side play an essential role in inhibition of urease activity. Lineweaver–Burk plots (kinetics study) indicated about 4b ...
Lectins are the oligomeric sugar-specific glycoprotein of nonimmune origin, are involved in the m... more Lectins are the oligomeric sugar-specific glycoprotein of nonimmune origin, are involved in the multiple biological recognition process, and have the capacity to perform a wide variety of physiological functions including antifungal, antiviral, antitumor, and cell agglutination. The main objective of the current study was to prepare lectin protein-loaded chitosan-TPP nanoparticles via ionic gelation methods with different CS/TPP ratios and to investigate anticancer potential against HepG2 cells. The best ratio showed the mean particle size ( 298.10 ± 1.9 nm, 21.05 ± 0.95 mv) with optimal encapsulation efficiencies of 52.435 ± 0.09 % . The cytotoxicity was evaluated against HepG2 cells, and IC50 values obtained were 265 μg/ml for lectin protein and 105 μg/ml for lectin-loaded chitosan-TPP nanoparticles, respectively. The mRNA expression of proliferation markers like GPC3 was significantly decreased in hepatocellular carcinoma cells (HepG2) during lectin protein-loaded chitosan-TPP ...
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