Papers by Alicja Nowaczyk
Farmacja Polska, Feb 7, 2024
Application of Artificial Neural Networks for Predicting Imidazole Derivatives' Antimicrobial Act... more Application of Artificial Neural Networks for Predicting Imidazole Derivatives' Antimicrobial Activity against Enterococcus faecalis Artificial neural networks (ANNs) have emerged as a valuable tool in facilitating the design of synthesis and guiding subsequent biological experiments in the systematic exploration for novel antimicrobial agents. In this paper, two multilayer perceptron-type neural networks (MLP) are designed to predict the biological activity of compounds based on their physicochemical properties and structure. This approach was tested against Enterococcus faecalis using a series of 140 imidazole derivatives. The use of quaternary ammonium salts in this research originated from their acknowledged ability to act as antiseptics and disinfectants. Additionally, they were considered promising in addressing various microorganisms, including Gram-positive bacteria. The designed regression model accurately predicted the minimum inhibitory concentration for E. faecalis growth. The coefficient of correlation between the actual values and the network predictions for the training set was R = 0.91, for the test set was R = 0.91, and for the validation set was R = 0.97.Additionally, the classification model successfully categorized the tested compounds as predictively active or inactive against the targeted microorganism (classification accuracy: 92.86%). Sensitivity analyses highlighted specific molecular descriptors
Journal of Pharmaceutical and Biomedical Analysis, Nov 1, 2009
Quantitative structure-retention relationships (QSRR) were proposed for alpha(1)-acid glycoprotei... more Quantitative structure-retention relationships (QSRR) were proposed for alpha(1)-acid glycoprotein (AGP) column using physicochemical molecular descriptors of the selected drugs and interacting with that column. The set of 52 structurally diverse drug compounds, with experimentally derived logarithms of retention factors (log k) values was considered. Thirty-six physicochemical property descriptors were calculated by standard molecular modeling and used to establish QSRR and predict the retention data by artificial neural network (ANN). The QSRR indicated that heat of formation (HF), Moriguchi n-octanol-water partition coefficient (M log P) and the energy of the highest occupied molecular orbital (HOMO) are the most important for interactions between drugs and AGP. The proposed ANN model based on selected molecular descriptors showed a high degree of correlation between log k observed and computed. The final model possessed a 36-5-1 architecture and correlation coefficients for learning, validating and testing sets equaled 0.975, 0.950 and 0.972, respectively.
Chemical Physics Letters, Nov 1, 2003
The atomic version of valence-universal coupled-clusters method in the intermediate Hamiltonian f... more The atomic version of valence-universal coupled-clusters method in the intermediate Hamiltonian formulation with one- and two-body part included in the cluster operator is applied to describe the ground state and some excited states of Li, B, Na, and Mg+ atomic systems. The Slater-type spdfg basis sets are employed. The results are corrected for the three-body cluster operator which is included
ACS Chemical Neuroscience, Sep 17, 2018
In this paper, we describe the latest results involving molecular modeling and pharmacodynamic st... more In this paper, we describe the latest results involving molecular modeling and pharmacodynamic studies of the selected highly lipophilic compounds acting by human GABA transporter 1 (hGAT1) inhibition. The chemical interaction of 17 GABA analogues with a model of hGAT1 is described using the molecular docking method. The biological role of GAT1 is related to the regulation of GABA level in the central nervous system and GAT1 inhibition plays an important role in the control of seizure threshold. To confirm that GAT1 can be also a molecular target for drugs used to treat other neurological and psychiatric diseases (e.g., pain and anxiety), in the in vivo part of this study, potential antinociceptive and anxiolytic-like properties of tiagabine, a selective GAT1 inhibitor, are described.
Medicinal Chemistry Research, Jan 7, 2011
The activity of a number of 1-[3-(4-arylpiperazin-1-yl)propyl]pyrrolidin-2-one antiarrhythmic (AA... more The activity of a number of 1-[3-(4-arylpiperazin-1-yl)propyl]pyrrolidin-2-one antiarrhythmic (AA) agents was described using the quantitative structureactivity relationship model by applying it to 33 compounds. The molecular descriptors of the AA activity were obtained by quantum chemical calculations combined with molecular modeling calculations. The resulting model explains up to 91% of the variance and it was successfully validated by four tests (LOO, LMO, external test, and Y-scrambling test). Statistical analysis shows that the AA activity of the studied compounds depends mainly on the PCR and JGI4 descriptors. Keywords 1-[3-(4-Arylpiperazin-1-yl)propyl]pyrrolidin-2-one derivatives Á Antiarrhythmic activity Á QSAR analysis Electronic supplementary material The online version of this article (
Biology and Life Sciences Forum, May 31, 2021
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Chemometrics and Intelligent Laboratory Systems, Mar 1, 2022
Research Square (Research Square), Dec 1, 2022
The paper discusses arti cial neural networks (ANNs) as a useful deep learning (DL) method to ass... more The paper discusses arti cial neural networks (ANNs) as a useful deep learning (DL) method to assist researchers in the search for new therapeutic and disinfectant substances. Two ANN models have been designed to predict the biological activity of the compounds based on their physicochemical properties and their structure. The said activity was tested against Enterococcus faecalis bacteria on a series of 140 imidazole derivatives. The regression model designed, predicted the minimum growth inhibitory concentration of E. faecalis (regression model: training data R = 0.91; test data R = 0.91; validation data R = 0.97). The classi cation model, on the other hand, divided the tested compounds into active or inactive against the tested microorganism predictive (classi cation accuracy: 92.86%). The exponential demand for new compounds in the pharmaceutical industry, requires alternative experimental methods to reduce the time and cost of development. Therefore, this paper proposes ANN as an alternative to standard techniques for predicting complex biological phenomena.
International Journal of Molecular Sciences, Jun 11, 2021
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Molecules, Jan 15, 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Talanta, 2015
The new type of stationary bonded phases for liquid chromatography with immobilized artificial me... more The new type of stationary bonded phases for liquid chromatography with immobilized artificial membrane properties was synthesized. Based on the modification of diol-bonded silica gel the cholesterol-ester and alkyl-ester stationary phases were obtained. The structures of synthesized material were confirmed by different physico-chemical techniques such as elemental analysis, infrared spectroscopy (FTIR), (13)C CP/MAS NMR and chromatography. Synthesized stationary phases were characterized and visualized by computer modeling that indicates the regions of potential hydrophobic and polar interactions. Synthesized material possess residual hydroxyl groups that reduce the hydrophobicity of the material and causes better stability at high water concentration. Due to surface properties these materials are became polar embedded stationary phases.
Molecules, Jun 4, 2021
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Journal of Chemical Physics, May 1, 2002
The atomically oriented valence-universal coupled-clusters method in the intermediate Hamiltonian... more The atomically oriented valence-universal coupled-clusters method in the intermediate Hamiltonian formulation with one- and two-body part(s) included in the cluster operator (VU-CCSD/R) is applied to describe the ground state and some excited states of the Mg atom. Two Slater-type orbitals (STO) basis sets are employed to see the effect of the basis set on the results. In addition to that, several complete model spaces are used in the calculation starting with (3s,3p) and ending with (3s,3p,3d,4s,4p) orbitals as active. It has been found that the quality of the description of the ground- and excited states depends on the STO basis set used in the calculation. In order to obtain reliable excitation energies, special attention has been paid to the construction of well-balanced basis sets in which functions necessary for adequate description of both the ground state and excited states under consideration are included. Therefore, in spite of the moderate size of the orbital basis, our results compare quite well in terms of the total energy as well as in energy differences with results of other methods which, in some cases, use significantly larger basis sets.
Pharmaceutics, Jan 18, 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Acta Poloniae Pharmaceutica, Sep 1, 2006
Amidrazones ñ hydrazones of acid amides as well as their derivatives have not been widely applied... more Amidrazones ñ hydrazones of acid amides as well as their derivatives have not been widely applied as therapeutics so far, although they exhibit significant biological activities e.g. antibacterial [1], antituberculitic [2, 3], antitumorus [4], antibacillary [5]. Amidrazones are also used for the synthesis of heterocyclic systems, 1,2,4ñtriazole derivatives [6, 7, 8]. Moreover the compounds, containing cyclic substituents (cyclopropyl, cyclohexyl, perhydrazepine) in their structure, exhibit cytotoxic activity [9, 10, 11]. Chemical part The paper presents reaction of N 3-substituted amidrazones [12], with 2ñcyclohexanedicarboxylic anhydride, resulting in new compounds, not reported in the literature. Compounds: N 3 ñ(2ñpyridyl)ñ2ñpicolinamidrazone 1, and N 3 ñ4ñnitrophenyl-2-picolylamidrazone 2, were chosen for the synthesis. The reaction was carried out in anhydrous diethyl ether at the room temperature and obtained products were purified by crystallization from methanol. In reaction of amidrazones 1 and 2 with the anhydride only linear derivatives were obtained: N 1-carbonylñ(-2ñcarboxycyclohexaneñ1ñyl)ñN 3 ñ(pyridin-2ñyl)ñ2ñpicolylamidrazone 3 and N 1-carbonyloñ(2ñcarb-oxycyclohexaneñ1ñyl)-N 3 ñ4-nitrophenylñ2ñpicolylamidrazone 4. The attempts of cyclization of compounds 3 and 4 at reflux in ethanol, butanol, and glacial acetic acid were not successful. The starting products were obtained in the unchanged form (Scheme 1). In the IR spectra of 3 and 4 characteristic absorption bands for the carbonyl group in the range 1693-1717 cm-1 were observed. In the 1 HNMR spectra for compounds 3, 4 there were found single signals of protons of carboxylic group in the range 11.9 ñ 12.1 ppm. The signals in the range 1.0 ñ 2.9 ppm were attributed to aliphatic protons from cyclohexane and in the range 6.7 ñ 8.7 ppm to protons of aromatic substituents. Compounds 3, 4 were characterized by additional absorption bands in the range 8.8 ñ 9.2 ppm in the form of a singlet to which protons of amide groups of amidrazone NH were attributed and in the range 9.5 ñ 11.9 ppm to protons of NH groups from the CONH groups. PHARMACOLOGICAL INVESTIGATIONS Compounds Stock solutions (10 and 100 mM) of tested compounds were prepared in DMSO
PubMed, Jan 7, 2010
A series of novel phenylpiperazine and phenylpiperidine derivatives bearing a 3,3-disubstituted p... more A series of novel phenylpiperazine and phenylpiperidine derivatives bearing a 3,3-disubstituted pyrrolidin-2-one fragment were synthesized and evaluated for their binding affinity for alpha1-adrenoceptors (ARs) and for their antiarrhythmic and antihypertensive activities. The highest affinity for alpha1-ARs was displayed by 1-[2-hydroxy-3-(4-phenylpiperazin-l-yl)-propyl]-3-phenyl-3-n-propyl-pyrrolidin-2-one (10 a), which binds with pK(i) = 6.43. Among the compounds tested, 1-(2-hydroxy-3-(4-phenylpiperidin-1-yl)-propylpyrrolidin-2-one (5) was the most active in the prophylactic antiarrhythmic activity in adrenaline induced arrhythmia in anesthetized rats. Its ED50 value was 4.9 mg/kg intravenously (i.v.). Some of the compounds tested significantly decreased the systolic and diastolic pressure in normotensive anesthetized rats at a dose of 5.0 mg/kg i.v. and their hypotensive effects lasted for longer than an hour.
Tetrahedron-asymmetry, Dec 1, 2015
The (R)-and (S)-enantiomers of 4-chloromethyl-1,3,2-dioxathiolane-2-oxide were used as 'epoxide-l... more The (R)-and (S)-enantiomers of 4-chloromethyl-1,3,2-dioxathiolane-2-oxide were used as 'epoxide-like' synthons in the asymmetric alkylation of the enantiomers of oxazinone-derived glycine equivalents. The configurations of the obtained spiro compounds were easily determined using 2D nuclear Overhauser effect nuclear magnetic resonance experiments. Additionally, the mechanisms of the reactions performed were explained using molecular modelling. The spiro derivatives obtained can also be modified and hydrolysed to their corresponding amino acids, which are derivatives of 1-aminocyclopropane-1-carboxylic acids.
Molecular Informatics, Mar 5, 2010
Arylpiperazines represent one of the most studied classes of α1 -adrenoceptor (α1 -AR) antagonist... more Arylpiperazines represent one of the most studied classes of α1 -adrenoceptor (α1 -AR) antagonists. Currently, α1 -AR antagonists are useful in the treatment of benign prostatic hyperplasia, lower urinary tract symptoms or cardiac arrhythmia. The activity of various derivatives of 1-[3-(4-arylpiperazin-1-yl)propyl]pyrrolidin-2-one as α1 -adrenergic receptor antagonists and antiarrhythmic (AA) agents was described using the qualitative inverse Structure Activity Relationship (SAR) model. The three-dimensional structures of the pyrrolidin-2-one derivatives in the basic form were obtained using AM1 semi-empirical quantum chemical calculations. All the molecules were geometry-optimized until the root-mean-square (RMS) gradient value was smaller than 10(-6) a.u. Single-point energy (SPE) calculations were performed at the DFT/B3LYP level of theory using the 6-31G** basis set. The main focus of this inverse SAR study is to find which features cause enhancing of antiarrhythmic properties between subtly different types of activity (α1 -adrenoreceptor antagonists and antiarrhythmic activities). Our SAR study involves the charge distribution in the plane of the pharmacophore model for α1 -AR. Suitable maps of the electrostatic potential were plotted based on the electronic and nuclear charge distribution obtained from the energy calculations. The results of this modelling study indicate that if the terminal arylpiperazine moiety is surrounded by regions of negative electrostatic potential, then the antiarrhythmic activity is blocked.
Journal of Molecular Graphics & Modelling, Oct 1, 2018
Docking and pharmacodynamic studies on hGAT1 inhibition activity in the presence of selected neur... more Docking and pharmacodynamic studies on hGAT1 inhibition activity in the presence of selected neuronal and astrocytic inhibitors. Part I
Current Drug Metabolism, Nov 5, 2020
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Papers by Alicja Nowaczyk