Synthesis, characterization, antituberculosis activity and computational studies on novel Schiff bases of 1,3,4- thiadiazole derivatives

Abstract

A series of novel Schiff bases were designed and synthesized by the condensation of 1,3,4-thiadiazoles that contain aromatic primary amine and variously substituted benzaldehydes. The synthesized compounds were screened for their antituberculosis activity against Mycobacterium tuberculosis H37Rv using BACTEC 460 radiometric system. Among the tested compounds, 2-(4-nitrophenyl)amino-5-[4-(3-(4-phenoxy))benzylideneaminophenyl]-1,3,4- thiadiazole (3n) showed the highest inhibitory activity (80%). The activities of the newly synthesized Schiff bases were higher in comparison to those of intermediate products 2-(4-aminophenyl)-5-aryl/alkylamino-1,3,4- thiadiazoles (2a-l). The computational studies were also performed to estimate drug-like profile of the compounds by using QikProp analysis.

Keywords

• Schiff bases
• 1,3,4-thiadiazoles
• antituberculosis activity
• Mycobacterium tuberculosis H37Rv
• ADME

References

1. [1] Rawat P, Singh RN, Niranjan P, Ranjan A, Holguin NRF. Evaluation of antituberculosis activity and DFT study ondipyrromethane-derived hydrazone derivatives. J Mol Struct. 2017; 1149: 539-548. [CrossRef]
2. [2] Clark MP, Wang T, Perola E, Deininger DD, Zuccola HJ, Jones SM, Gao H, VanderVen BC, Russel DG, Shoen CM, Cynamon MH, Thompson JA, Locher CP. 2-N-Arylthiazole inhibitors of Mycobacterium tuberculosis. Bioorg Med Chem Lett. 2017; 27: 3987-3991. [CrossRef]
3. [3] WHO Global tuberculosis report 2019. http://www.who.int/tb/publications/global_report/en/ (accessed on 14 July 2020).
4. [4] Mandewale MC, Patil UC, Shedge SV, Dappadwad UR, Yamgar RS. A review on quinoline hydrazone derivatives as a new class of potent antitubercular and anticancer agents. Beni-Suef Univ J Basic Appl Sci. 2017; 6: 354-361. [CrossRef]
5. [5] Velezheva V, Brennan P, Ivanov P, Kornienko A, Lyubimov S, Kazarian K, Nikonenko B, Majorov K, Apt A. Synthesis and antituberculosis activity of indole-pyridine derived hydrazides, hydrazide-hydrazones, and thiosemicarbazones. Bioorg Med Chem Lett. 2016; 26: 978-985. [CrossRef]
6. [6] Pawaiya A, Pawaiya P, Rajput S, Agrawal MC, Bhatnagar RK. Synthesis, characterization and antifungal activity of hydrazone Schiff base. Int J Curr Res. 2014; 6(9): 8423-8426.
7. [7] Al-Masoudi WA, Al-Tememy TM, Al-Assadi RH. Computational study and antimicrobial activity of few Dapsone Schiff base derivatives. Eur J Chem. 2014; 5(2): 351-355. [CrossRef]
8. [8] Batra N, Batra S, Aggarwal N, Nagori BP. Schiff bases as CNS active agents: a review. Am J PharmTech Res. 2013; 3(4): 1-19.

9. [9] Ejidike IP, Ajibade PA. Transition metal complexes of symmetrical and asymmetrical Schiff bases as antibacterial, antifungal, antioxidant, and anticancer agents: progress and prospects. Rev Inorg Chem 2015; 35(4): 191-224. [CrossRef]
10. [10] Nath M, Saini PK, Kumar A. New di- and triorganotin (IV) complexes of tripodal Schiff base ligand containing three imidazole arms: Synthesis, structural characterization, anti-inflammatory activity and thermal studies. J Organomet Chem. 2010; 695: 1353-1362. [CrossRef]
11. [11] Zoubi WA, Al-Hamdani AAS, Kaseem M. Synthesis and antioxidant activities of Schiff bases and their complexes: a review. Appl Organomet Chem. 2016; 30: 810-817. [CrossRef]
12. [12] Baran NY, Karakışla M, Demir HÖ, Saçak M. Synthesis, characterization, conductivity and antimicrobial study of a novel thermally stable polyphenol containing azomethine group. J Mol Struct. 2016; 1123: 153-161. [CrossRef]
13. [13] Matysiak J. Biological and pharmacological activities of 1,3,4-thiadiazole based compounds. Mini Rev Med Chem. 2015; 15(9): 762-775. [CrossRef]
14. [14] Pandey A, Dewangan D, Verma S, Mishra A, Dubey RD. Synthesis of Schiff bases of 2-amino-5-aryl-1,3,4-thiadiazole and its analgesic, antiinflammatory, anti-bacterial and antitubercular activity. Int J ChemTech Res. 2011; 3(1): 178- 184.
15. [15] Hwang TJ, Wares DF, Jafarov A, Jakubowiak W, Nunn P, Keshavjee S. Safety of cycloserine and terizidone for the treatment of drug-resistant tuberculosis: a meta-analysis. Int J Tuberc Lung Dis. 2013; 17(10): 1257–1266. [CrossRef]
16. [16] Foroumadi A, Kiani Z, Soltani F. Antituberculosis agents VIII. Synthesis and in vitro antimycobacterial activity of alkyl alpha-[5-(5-nitro-2-thienyl)-1,3,4-thiadiazole-2-ylthio]acetates. Farmaco. 2003; 58: 1073-1076. [CrossRef]
17. [17] Kolavi G, Hegde V, Khazi IA, Gadad P. Synthesis and evaluation of antitubercular activity of imidazo[2,1- b][1,3,4]thiadiazole derivatives. Bioorg Med Chem 2006; 14: 3069-3080. [CrossRef]
18. [18] Karakuş S, Rollas S. Synthesis and antimycobacterial activity of some 2-(4-aminophenyl)- 5-substituted amino-1,3,4- thiadiazole derivatives and their coupling products. Marmara Pharm J. 2016; 20: 199-206. [CrossRef]
19. [19] Chitra S, Paul N, Muthusubramanian S, Manisankar P, Yogeeswari P, Sriram D. Synthesis of 3- heteroarylthioquinoline derivatives and their in vitro antituberculosis and cytotoxicity studies. Eur J Med Chem. 2011; 46: 4897-4903. [CrossRef]
20. [20] Oruc EE, Rollas S, Kandemirli F, Shvets N, Dimoglo AS. 1,3,4-Thiadiazole derivatives. Synthesis, structure elucidation, and structure−antituberculosis activity relationship investigation. J Med Chem. 2004; 47: 6760-6767. [CrossRef]
21. [21] Tatar E, Küçükgüzel ŞG, Karakuş S, De Clercq E, Andrei G, Snoeck R, Pannecouque C, Öktem Okullu S, Ünübol N, Kocagöz T, Kalaycı S, Şahin F, Küçükgüzel İ. Synthesis and biological evaluation of some new 1,3,4-thiadiazole and 1,2,4-triazole derivatives from L-methionine as antituberculosis and antiviral agents. Marmara Pharm J. 2015; 19: 88- 102. [CrossRef]
22. [22] Küçükgüzel ŞG, Küçükgüzel İ, Tatar E, Rollas S, Şahin F, Güllüce M, Clercq ED, Kabasakal L. Synthesis of some novel heterocyclic compounds derived from diflunisal hydrazide as potential anti-infective and anti-inflammatory agents. Eur J Med Chem. 2007; 42: 893-901. [CrossRef]
23. [23] Solak N, Rollas S. Synthesis and antituberculosis activity of 2-(aryl/alkylamino)-5-(4-aminophenyl)-1,3,4- thiadiazoles and their Schiff bases. ARKIVOC. 2006; 12: 173-181. [CrossRef]
24. [24] Suleymanoglu N, Ustabas R¸ Alpaslan YB, Coruh U, Karakus S¸ Rollas S. 2-Propylamino-5-[4-(2-hydroxy-3,5- dichlorobenzylideneamino) phenyl]-1,3,4-thiadiazole: X-ray and DFT-calculated structures. Struct Chem. 2010; 21: 59-65. [CrossRef]
25. [25] Güngör Ö, Gürkan P. Synthesis and spectroscopic properties of novel asymmetric Schiff bases. Spectrochim Acta Mol Biomol Spectros. 2010; 77: 304-311. [CrossRef]
26. [26] Tahtaci H, Karacı H, Ece A, Er M, Şeker MG. Design, synthesis, SAR and molecular modeling studies of novel imidazo [2,1-b][1,3,4]thiadiazole derivatives as highly potent antimicrobial agents. Mol Inform. 2018; 37(3): 1700083. [CrossRef]
27. [27] Ece A. Towards more effective acetylcholinesterase inhibitors: a comprehensive modelling study based on human acetylcholinesterase protein–drug complex. J Biomol Struct Dyn. 2020; 38(2): 565-572. [CrossRef]
28. [28] Vistoli G, Pedretti A, Testa B. Assessing drug-likeness – what are we missing? Drug Discov Today. 2008; 13(7): 285- 294. [CrossRef]
29. [29] Karakus S, Rollas S. Synthesis and antituberculosis activity of new N-phenyl-N′-[4-(5-alkyl/arylamino-1,3,4- thiadiazole-2-yl)phenyl]thioureas. Farmaco 2002; 57: 577-581. [CrossRef]
30. [30] Collins LA, Franzblau SG. Microplate alamar blue assay versus BACTEC 460 system for high-throughput screening of compounds against Mycobacterium tuberculosis and Mycobacterium avium. Antimicrob Agents Chemother. 1997; 41(5): 1004-1009.
31. [31] Schrödinger Release 2019-3: LigPrep, Schrödinger, LLC, New York, NY, 2019.
32. [32] Shelley JC, Cholleti A, Frye LL, Greenwood JR, Timlin MR, Uchimaya M. Epik: a software program for pKa prediction and protonation state generation for drug-like molecules. J Comput Aided Mol Des. 2007; 21 (12): 681-691. [CrossRef]
33. [33] Er M, Abounakhla AM, Tahtaci H, Bawah AH, Çınaroğlu SS, Onaran A, Ece A. An integrated approach towards the development of novel antifungal agents containing thiadiazole: synthesis and a combined similarity search, homology modelling, molecular dynamics and molecular docking study. Chem Cent J. 2018; 12 (1): 121. [CrossRef]
34. [34] Maryam A, Khalid RR, Siddiqi AR, Ece A. E-pharmacophore based virtual screening for identification of dual specific PDE5A and PDE3A inhibitors as potential leads against cardiovascular diseases. J Biomol Struct Dyn. 2020; 1-16. [CrossRef]