The Pharmacophore Model for the Antistaphylococcal Activity Screening Among Thiazolidinone-Related Structures

R. B. Vinnitska, O. T. Devinyak, A. V. Lozynskyi, S. M. Holota, H. O. Derkach, Ya. I. Deyak, R. V. Kutsyk, R. B. Lesyk


Aim. To develop a pharmacophore model suitable for the antistaphylococcal activity screening among thiazolidinone, thiopyrano[2,3-d]thiazole and thiazolo[4,5-b]pyridine derivatives.

Results and discussion. The best pharmacophore model in the series of models developed has a planar structure and consists of an aromatic ring (or cycle with π-bonds), a hydrophobic region, a projection of a hydrogen bond donor and two projections of a hydrogen bond acceptor. Its classification accuracy is 72.4 %. The diameter line of the model is formed by the projection of the hydrogen bond donor and the projection of the hydrogen bond acceptor, and its length is 8.05 Å. The analysis of conformations of active compounds consistent with the pharmacophore mode revealed two different ways of spatial arrangement of active molecules, in which the conditions of the pharmacophore model are fully met.

Experimental part. The antistaphylococcal activity was determined by the agar diffusion method against methicillin-resistant strain of Staphylococcus aureus (MRSA) and evaluated by measuring the diameter of the microbial growth inhibition zone. The plates were incubated for 24 h at 37 °C. Compounds with the growth inhibition diameter of more than 7.5 mm were considered to be active. Computer processing of the results of the microbiological experiment and modeling of the probable pharmacophore were performed in the MOE software environment version 2007.09. The geometry of the compounds was optimized by molecular mechanics using the MMFF94x force field. Accuracy of classification was used as the main quality criterion of the pharmacophore model.

Conclusions. The pharmacophore model developed can be used for virtual screening of the antistaphylococcal activity for the compounds similar to the training sample. When applying it to the in-home database of compounds the enrichment factor is EF = 2.05.

Received: 27.09.2020
Revised: 23.10.2020
Accepted: 03.11.2020


chemoinformatics; 4-thiazolidinones; pharmacophore modeling; antibacterial activity


Lesyk, R. Drug design: 4-thiazolidinones applications. Part 1. Synthetic routes to the drug-like molecules. Journal of Medical Science 2020, 89 (2), e406.

Lesyk, R. Drug design: 4-thiazolidinones applications. Part 2. Pharmacological profiles. Journal of Medical Science 2020, 89 (2), e407.

Brown, F. C. 4-Thiazolidinones. Chem. Rev. 1961, 61 (5), 463–521.

Singh, S. P.; Parmar, S. S.; Raman, K.; Stenberg, V. I. Chemistry and biological activity of thiazolidinones. Chem. Rev. 1981, 81 (2), 175–203.

Sim, M. M.; Ng, S. B.; Buss, A. D.; Crasta, S. C.; Goh, K. L.; Lee, S. K. Benzylidene Rhodanines as Novel Inhibitors of UDP-N-Acetylmuramate/L-Alanine Ligase. Bioorg. Med. Chem. Lett. 2002, 12 (4), 697–699.

Brooke, E. W.; Davies, S. G.; Mulvaney, A. W.; Okada, M.; Pompeo, F.; Sim, E.; Vickers, R. J.; Westwood, I. M. Synthesis and in vitro evaluation of novel small molecule inhibitors of bacterial arylamine N-acetyltransferases (NATs). Bioorg. Med. Chem. Lett. 2003, 13 (15), 2527–2530.

Carlson, E. E.; May, J. F.; Kiessling, L. L. Chemical Probes of UDP-Galactopyranose Mutase. Chem. Biol. 2006, 13 (8), 825–837.

Soltero-Higgin, M.; Carlson, E. E.; Phillips, J. H.; Kiessling, L. L. Identification of Inhibitors for UDP-Galactopyranose Mutase. J. Am. Chem. Soc. 2004, 126 (34), 10532–10533.

Holota, S. М.; Derkach, G. О.; Zasidko, V. V.; Trokhymchuk, V. V.; Furdychko, L. O.; Demchuk, I. L.; Semenciv, G. M.; Soronovych, I. I.; Kutsyk, R. V.; Lesyk, R. B. Antimicrobial activity of some 5-aminomethylene-2-thioxo-4-thiazolidinones. Biopolym. Cell 2019, 35 (5), 371–380.

Lozynskyi, A.; Zasidko, V.; Atamanyuk, D.; Kaminskyy, D.; Derkach, H.; Karpenko, O.; Ogurtsov, V.; Kutsyk, R.; Lesyk, R. Synthesis, antioxidant and antimicrobial activities of novel thiopyrano[2,3-d]thiazoles based on aroylacrylic acids. Mol. Divers. 2017, 21 (2), 427–436.

Lozynskyi, A.; Zimenkovsky, B.; Radko, L.; Stypula-Trebas, S.; Roman, O.; Gzella, A. K.; Lesyk, R. Synthesis and cytotoxicity of new thiazolo[4,5-b]pyridine-2(3H)-one derivatives based on α,β-unsaturated ketones and α-ketoacids. Chem. Pap. 2018, 72 (3), 669–681.


Howard, M. H.; Cenizal, T.; Gutteridge, S.; Hanna, W. S.; Tao, Y.; Totrov, M.; Wittenbach, V. A.; Zheng, Y.-j. A Novel Class of Inhibitors of Peptide Deformylase Discovered through High-Throughput Screening and Virtual Ligand Screening. J. Med. Chem. 2004, 47 (27), 6669–6672.

Devinyak, O.; Zimenkovsky, B.; Lesyk, R. Biologically Active 4-Thiazolidinones: A Review of QSAR Studies and QSAR Modeling of Antitumor Activity. Curr. Top. Med. Chem. 2012, 12 (24), 2763–2784.

Zimenkovsky, B. S.; Devinyak, O. T.; Lesyk, R. B. Modeling of a possible pharmacophore group for 4-thiazolidinones with the anticancer activity. Journal of Organic and Pharmaceutical Chemistry 2012, 10 (4), 76–82.

MOE, 2007.09 (Molecular Operating Environment software); Chemical Computing Group Inc.

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Abbreviated key title: J. Org. Pharm. Chem.

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