Synthesis and in-silico evaluation of some new 2,4-disubstituted thiazole derivatives

Year 2022, Volume: 1 Issue: 1, 8 - 19, 29.04.2022

Leyla Yurttaş , Asaf Evrim Evren , Yusuf Özkay

https://doi.org/10.55971/EJLS.1089425

Abstract

The synthesis and anti-proliferative activity investigation of methyl 3/4-[[4-(2-substituted thiazol-4-yl)phenyl]amino]-3-oxopropanoate/(4-oxobutanoate) (3a-h) derivatives were aimed in this work. The synthesis of the new compounds were carried out by a simple, multiple-step synthetic procedure. The physicochemical properties of the compounds were determined using SwissADME and QuickProp software systems. Additionally, virtual target and toxicity predictions were carried out for all final compounds. The pharmacokinetics/physicochemical, druglikeness properties and biological target and toxicity predicitions of the compounds were determined to possess satisfying findings. Since the target determination of the compounds according to literature is point out their cytotoxic properties, the DNA gyrase enzyme was chosen as common enzymatic pathway, and evaluated via docking studies. Compound 3b, namely methyl 4-[[4-(2-methylthiazol-4-yl)phenyl]amino]-4-oxobutanoate was detected to possess a potential to inhibit DNA gyrase-ATPase activity.

Keywords

DNA gyrase inhibition, druglikeness, molecular docking, pharmacokinetic properties, thiazole

References

• 1. Nayak S, Gaonkar SL. A Review on recent synthetic strategies and pharmacological importance of 1,3-thiazole derivatives. Mini Rev Med Chem. (2019);19:215-38 https://doi.org/10.2174/1389557518666180816112151
• 2. Yılmaz Cankılıç M, Yurttaş L. Study on the antimicrobial effects of novel thiazole derivatives. Marmara Pharm J. (2017);21(3):654-659 https://doi.org/10.12991/marupj.323584
• 3. Kashyap SJ, Vipin Kumar G, Kumar Sharma P, Kumar N, Dudhe R, Kumar Gupta J. Thiazoles: having diverse biological activities. Med Chem Res. (2012);21:2123–32 https://doi.org/ 10.1007/s00044-011-9685-2
• 4. Bourgaud F, Gravot A, Milesi, S, Gontier E. Production of plant secondary metabolites: a historical perspective. Plant Sci. (2001);161(5):839–51 https://doi.org/10.1016/S0168-9452(01)00490-3
• 5. Rouf A, Tanyeli C. Bioactive thiazole and benzothiazole derivatives. Eur J Med Chem. (2015):97;911-27 https://doi.org/10.1016/j.ejmech.2014.10.058
• 6. Akbarzadeh A, Soleymani R, Taheri M, Karimi-Cheshmeh Ali M. Synthesis new and novel aryl thiazole derivatives compounds. Orient J Chem. (2012);28(1): 153-64 https://doi.org/10.13005/ojc/280122
• 7. Deepti V, Aruna Kumari M, Harikrishna N, Ramesh G, Venkata Rao C. Synthesis of novel 2-amino thiazole derivatives. Der Pharm Chem. (2013);5(2):181-84 https://www.derpharmachemica.com/pharma-chemica/synthesis-of-novel-2amino-thiazole-derivatives.pdf
• 8. Chhabriaa MT, Patel S, Modi P, Brahmkshatriya PS. Thiazole: A review on chemistry, synthesis and therapeutic importance of its derivatives. Curr Top Med Chem. (2016);16: 2841-62 https://doi.org/10.2174/1568026616666160506130731
• 9. Ibrahım Mohamed SS. Synthesis of New Thiazole Derivatives Bearing a Sulfonamide Moiety of Expected Anticancer and Radiosensitizing Activities [Master Thesis]. Cairo: Cairo University; (2012).
• 10. Kashyap A, Adhikari N, Das A, Shakya A, Kumar Ghosh S, Pratap Singh U, Bhat HR. Review on synthetic chemistry and antibacterial importance of thiazole derivatives. Curr Drug Dis Techno. (2018);15:214-28 https://doi.org/ 10.2174/1570163814666170911144036
• 11. Tomassetti M, Lupidi G, Piermattei P, Rossi FV. Lillini S, Bianchini G, Aramini A, Ciufolini MA, Marcantoni E. Catalyst-free synthesis of polysubstituted 5-acylamino-1,3-thiazoles via Hantzsch cyclization of α-chloroglycinates. Molecules (2019);24:3846 https://doi.org/10.3390/molecules24213846
• 12. Evren AE, Yurttas L, Ekselli B, Akalin-Ciftci G. Synthesis and biological evaluation of 5-methyl-4-phenyl thiazole derivatives as anticancer agents. Phosphorus Sulfur Silicon Relat Elem. (2020);194(8):820-28 https://doi.org/10.1080/10426507.2018.1550642
• 13. Kashyap SJ, Garg VK, Sharma PK, Kumar N, Dudhe R, Gupta JK. Thiazoles: having diverse biological activities. Med Chem Res. (2012);21:2123–32 https://doi.org/ 10.1007/s00044-011-9685-2
• 14. Sahin Z, Ertas M, Bender C, Bülbül EF, Berk B, Biltekin SN, Yurttas L, Demirayak Ş. Thiazole-substituted benzoylpiperazine derivatives as acetylcholinesterase inhibitors. Drug Dev Res. (2018);1–20 https://doi.org/10.1002/ddr.21481
• 15. Siddiqui N, Arshad MF, Ahsan W, Alam MS. Thiazoles: A valuable insight into the recent advances and biological activities. Inter J Pharma Sci Drug Res. (2009);1(3): 136-43 https://ijpsdr.com/index.php/ijpsdr/article/view/46
• 16. Doregiraee A, Kermani ET, Khabazzadeh H, Pouramiri B. Synthesis of new 1,3-thiazole derivatives; using 1-(4-carbamoylphenyl)-3- methylthiourea and 1-methyl-3-(quinolin-8-yl)thiourea as starting materials. J Chil Chem Soc. (2015);6:3021-23 http://dx.doi.org/10.4067/S0717-97072015000300009
• 17. Gaikwad SA, Patil AA, Deshmukh MB. An efficient, uncatalyzed, and rapid synthesis of thiazoles and aminothiazoles under microwave irradiation and investigation of their biological activity. Phosphorus Sulfur Silicon Relat Elem. (2010);185:103–9 https://doi.org/10.1080/10426500802715163
• 18. Yurttas L, Ozkay Y, Demirci F, Göger G, Ulusoylar-Yıldırım Ş, Abu Mohsen U, Öztürk Ö, Kaplancıklı ZA. Turk J Chem. (2014);38:815-24 https://doi.org/10.3906/kim-1312-62
• 19. Maienfisch P, Edmunds AJF. Thiazole and isothiazole ringe containing compounds in crop protection. Adv Heterocyc Chem. (2010);121:35-88 https://doi.org/10.1016/bs.aihch.2016.04.010
• 20. Ayati A, Emami S, Asadipour A, Shafiee A, Foroumadi A. Recent applications of 1,3-thiazole core structure in the identification of new lead compounds and drug discovery. Eur J Med Chem. (2015);97:699-718 https://doi.org/10.1016/j.ejmech.2015.04.015
• 21. Ayati A, Emami S, Moghimi S, Foroumadi A. Thiazole in the targeted anticancer drug discovery. Future Med Chem. (2019);11(15):1929-52 https://doi.org/10.4155/fmc-2018-0416
• 22. Özkay Y, Yurttas L¸ Dikmen M, Engur S. Synthesis and antiproliferative activity evaluation of new thiazole–benzimidazole derivatives using real-time cell analysis (RTCA DP). Med Chem Res. (2016);25:482–93 https://dx.doi.org/10.1007/s00044-016-1507-0
• 23. Yurttaş L, Özkay Y, Akalın-Ciftci G, Ulusoylar-Yıldırım Ş. Synthesis and anticancer activity evaluation of N-[4-(2-methylthiazol-4-yl)phenyl]acetamide derivatives containing (benz)azole moiety. J Enzyme Inhib Med Chem. (2014);29(2):175–184 https://doi.org/10.3109/14756366.2013.763253
• 24. Yurttaş L, Kaplancıklı ZA, Özkay Y. Design, synthesis and evaluation of new thiazole-piperazines as acetylcholinesterase inhibitors. J Enzyme Inhib Med Chem. (2013);28(5):1040–47 https://doi.org/10.3109/14756366.2012.709242
• 25. Yurttaş L, Demir B, Akalın-Çiftçi G. Some thiazole derivatives combined with different heterocycles: cytotoxicity evaluation and apoptosis inducing studies. Anticancer Agents Med Chem. (2018);18:1115-21 https://doi.org/10.2174/1871520618666180328115314
• 26. Demirayak Ş, Şahin Z, Ertaş M, Bülbül EF, Bender C, Biltekin SN, Berk B, Sağlık BN, Levent S, Yurttaş L. Novel thiazole‐piperazine derivatives as potential cholinesterase inhibitors. J Heterocyclic Chem. (2019);1–17 https://doi.org/10.1002/jhet.3734
• 27. SwissADME. Swiss Institute of Bioinformatics. (2021). Retrieved 15 January, 2022 from http://www.swissadme.ch/
• 28. QikProp. Rapid ADME predictions of drug candidates. (2022). Retrieved 25 January, 2022 from https://www.schrodinger.com/qikprop
• 29. SwissTargetPrediction. Swiss Institute of Bioinformatics. (2021). Retrieved 20 January, 2022 from http://www.swisstargetprediction.ch/
• 30. pkCSM, Pharmacokinetic properties. (2021). Retrieved 10 June, 2021 from http://biosig.unimelb.edu.au/pkcsm/admet_prediction
• 31. 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);7:427 https://doi.org/10.1038/srep42717
• 32. 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 (2001);46;3–26 https://doi.org/ 10.1016/s0169-409x(00)00129-0
• 33. Ghose AK, Viswanadhan VN, Wendoloski JJ. A knowledge-based approach in designing combinatorial or medicinal chemistry libraries for drug discovery. A qualitative and quantitative characterization of known drug databases. J Comb Chem. (1999);1:55–68 https://doi.org/10.1021/cc9800071
• 34. Teague S, Davis A, Leeson P, Oprea T. The design of leadlike combinatorial libraries. Angew Chem Int Ed Engl (1999):38;3743–48 https://doi.org/10.1002/(SICI)1521-3773(19991216)38:24<3743::AID-ANIE3743>3.0.CO;2-U
• 35. Tukur M, Adamu I, Gideon U, Shallangwa A, Uba S. In-silico activity prediction and docking studies of some 2,9-disubstituted 8-phenylthio/phenylsulfinyl-9h-purine derivatives as anti-proliferative agents. Heliyon (2020);6:e03158 https://doi.org/10.1016/j.heliyon.2020.e03158
• 36. Enmozhi SK, Raja K, Sebastine I, Joseph J. Andrographolide as a potential inhibitor of SARS-CoV-2 main protease: an in silico approach. J Biomol Struct Dyn. (2020);1–7 https://doi.org/10.1080/07391102.2020.1760136
• 37. Durcik, M, Nyerges, A, Skok Z, Skledar DG, Trontelj J, Zidar N, Ilas J, Zega A, Cruz CD, Tammela P, Welin M, Kimbung YR, Focht D, Benek O, Revesz T, Draskovits G, Szili PE, Daruka L, Pal C, Kikelj D, Masic LP, Tomasic T. New dual ATP-competitive inhibitors of bacterial DNA gyrase and topoisomerase IV active against ESKAPE pathogens. Eur J Med Chem (2021);213;113200 https://doi.org/10.1016/j.ejmech.2021.113200
• [38] Durcik M, Lovison D, Skok Z, Durante Cruz C, Tammela P, Tomasic T, Benedetto Tiz D, Draskovits G, Nyerges A, Pal C, Ilas J, Peterlin Masic L, Kikelj D, Zidar N. New N-phenylpyrrolamide DNA gyrase B inhibitors: Optimization of efficacy and antibacterial activity. Eur J Med Chem. (2018):154;117-32 https://doi.org/10.1016/j.ejmech.2018.05.011
• [39] Wang S, Li Y, Xu L, Li D, Hou T. Recent developments in computational prediction of HERG blockage. Curr Top Med Chem. (2013):13;1317-26 https://doi.org/10.2174/15680266113139990036