Synthesis, biological activity evaluation and molecular docking studies of novel thiazole derivatives

Abstract

Resistance to existing drugs develops because of insensible use of antibacterial and antifungal drugs. Therefore, there is a need for the development of new drug candidate compounds. The thiazole ring has many biological activities. It is possible to include antibacterial and antifungal activities among these activities. In addition to these, the thiazole ring has been preferred because it is the bioisostere of the imidazole ring in the structure of many antifungal drugs. For this purpose, within the scope of this study, 7 new thiazole compounds were synthesized, and their structure determinations were carried out using HRMS, 1H-NMR, 13C-NMR spectroscopic methods. Their antibacterial and antifungal activities were investigated by in vitro methods. As a result of activity tests, compound 3e showed activity against C.krusei strain with MIC50=31.25 ug/mL. The potential effectiveness of the compound 3e on the 14alpha-demethylase enzyme (PDB ID:3LD6) was tested by in silico studies.

Keywords

• Thiazole
• Antibacterial Activity
• Antifungal Activity
• Molecular Docking

References

1. Yang XC, Zeng CM, Avula SR, Peng XM, Geng RX, Zhou CH. Novel coumarin aminophosphonates as potential multitargeting antibacterial agents against Staphylococcus aureus. Eur. J. Med. Chem. (2023); 245: 114891. https://doi.org/10.1016/j.ejmech.2022.114891
2. Zhou XM, Hu YY, Fang B, Zhou CH. Benzenesulfonyl thiazoloimines as unique multitargeting antibacterial agents towards Enterococcus faecalis. Eur. J. Med. Chem. (2023); 115088. https://doi.org/10.1016/j.ejmech.2023.115088
3. Rashdan HR, Abdelmonsef AH, Abou-Krisha MM, Yousef TA. Synthesis, identification, computer-aided docking studies, and ADMET prediction of novel benzimidazo-1, 2, 3-triazole based molecules as potential antimicrobial agents. Molecules (2021); 26(23): 7119. https://doi.org/10.3390/molecules26237119
4. Niu ZX, Wang YT, Zhang SN, Li Y, Chen XB, Wang SQ, Liu HM. Application and synthesis of thiazole ring in clinically approved drugs. Eur. J. Med. Chem (2023); 250: 115172. https://doi.org/10.1016/j.ejmech.2023.115172
5. Hussein AHM, El-Adasy ABA, El-Saghier AM, Olish M, Abdelmonsef AH. Synthesis, characterization, in silico molecular docking, and antibacterial activities of some new nitrogen-heterocyclic analogues based on ap-phenolic unit. RSC Adv. (2022); 12(20): 12607-12621. https://doi.org/10.1039%2Fd2ra01794f
6. Mokariya JA, Rajani DP, Patel MP. 1, 2, 4‐Triazole and benzimidazole fused dihydropyrimidine derivatives: Design, green synthesis, antibacterial, antitubercular, and antimalarial activities. Arch. Pharm. (2022); e2200545. https://doi.org/10.1002/ardp.202200545
7. Nural Y, Ozdemir S, Yalcin MS, Demir B, Atabey H, Seferoglu Z, Ece A. New bis-and tetrakis-1, 2, 3-triazole derivatives: Synthesis, DNA cleavage, molecular docking, antimicrobial, antioxidant activity and acid dissociation constants. Bioorg. Med. Chem. Lett. (2022); 55: 128453. https://doi.org/10.1016/j.bmcl.2021.128453
8. Hu Y, Hu C, Pan G, Yu C, Ansari MF, Bheemanaboina RRY, Cheng Y, Chenghe Z, Zhang, J. Novel chalcone-conjugated, multi-flexible end-group coumarin thiazole hybrids as potential antibacterial repressors against methicillin-resistant Staphylococcus aureus. Eur. J. Med. Chem. (2021); 222: 113628. https://doi.org/10.1016/j.ejmech.2021.113628

9. Sucharitha ER, Krishna TM, Manchal R, Ramesh G, Narsimha S. Fused benzo [1, 3] thiazine-1, 2, 3-triazole hybrids: Microwave-assisted one-pot synthesis, in vitro antibacterial, antibiofilm, and in silico ADME-studies. Bioorg. Med. Chem. Lett. (2021); 47: 128201. https://doi.org/10.1016/j.bmcl.2021.128201
10. Gondru R, Kanugala S, Raj S, Kumar CG, Pasupuleti M, Banothu J, Bavantula R. 1, 2, 3-triazole-thiazole hybrids: Synthesis, in vitro antimicrobial activity and antibiofilm studies. Bioorg. Med. Chem. Lett. (2021); 33: 127746. https://doi.org/10.1016/j.bmcl.2020.127746
11. Salih RHH, Hasan AH, Hussen NH, Hawaiz FE, Hadda TB, Jamalis J, Almalki FA, Adeyinka AS, Coetzee LCC, Oyebamiji, AK. Thiazole-pyrazoline hybrids as potential antimicrobial agent: synthesis, biological evaluation, molecular docking, DFT studies and POM-analysis. J. Mol. Struct. (2023); 1282(10): 135191. https://doi.org/10.1016/j.molstruc.2023.135191
12. Alqurashi RM, Farghaly TA, Sabour R, Shaabana MR. Design, Synthesis, antimicrobial screening and molecular modeling of novel 6, 7 dimethylquinoxalin-2 (1H)-one and thiazole derivatives targeting DNA gyrase enzyme. Bioorg. Chem. (2023); 134: 106433. https://doi.org/10.1016/j.bioorg.2023.106433
13. Nandurkar Y, Shinde A, Bhoye MR, Jagadale S, Mhaske PC. Synthesis and biological screening of new 2-(5-Aryl-1-phenyl-1H-pyrazol-3-yl)-4-aryl thiazole derivatives as potential antimicrobial agents. ACS Omega (2023); 8(9):8743-8754. https://doi.org/10.1021/acsomega.2c08137
14. Meng F, Yan Z, Lu Y, Wang X. Design, synthesis, and antifungal activity of flavonoid derivatives containing thiazole moiety. Chem. Pap. (2022); 77:877-885. https://doi.org/10.1007/s11696-022-02522-4
15. Jagadeesan S, Karpagam S. Novel series of N-acyl substituted indole based piperazine, thiazole and tetrazoles as potential antibacterial, antifungal, antioxidant and cytotoxic agents, and their docking investigation as potential Mcl-1 inhibitors. J. Mol. Struct. (2023); 1271: 134013. https://doi.org/10.1016/j.molstruc.2022.134013
16. Wikler MA. Methods for dilution antimicrobial susceptibility tests for bacteria that growl aerobically: approved standard. Clsi (Nccls) (2006); 26: M7-A7.
17. Evren AE, Dawbaa S, Nuha D, Yavuz ŞA, Gül ÜD, Yurttaş L. Design and synthesis of new 4-methylthiazole derivatives: In vitro and in silico studies of antimicrobial activity. J. Mol. Struct. (2021); 1241: 130692. https://doi.org/10.1016/j.molstruc.2021.130692
18. Swiss Institute of Bioinformatics. SwissADME. Retrieved December 1 2022 from http://www.swissadme.ch/index.php#
19. Strushkevich N, Usanov SA, Park HW. Structural basis of human CYP51 inhibition by antifungal azoles. J. Mol. Biol. (2010); 397(4): 1067-1078. https://doi.org/10.1016/j.jmb.2010.01.075
20. Maestro, Schrödinger, LLC: New York, NY, USA 2020.
21. Schrödinger, Schrödinger, LLC, New York, NY, USA 2020.
22. Schrödinger, Schrödinger, LLC: New York, NY, USA 2020.
23. Borra RC, Lotufo MA, Gagioti SM, Barros FDM, Andrade PM. A simple method to measure cell viability in proliferation and cytotoxicity assays. Braz. Oral. Res. (2009); 23: 255-262. https://doi.org/10.1590/S1806-83242009000300006
24. Palomino JC, Martin A, Camacho M, Guerra H, Swings J, Portaels F. Resazurin microtiter assay plate: simple and inexpensive method for detection of drug resistance in Mycobacterium tuberculosis. AMACCQ (2022); 46(8): 2720-2722. https://doi.org/10.1128/AAC.46.8.2720-2722.2002
25. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. (2012); 64: 4-17. https://doi.org/10.1016/S0169-409X(00)00129-0
26. Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep. (2017); 7(1): 42717.