Synthesis, characterization and biological evaluation of 1,3-thiazolidine-4-ones derived from (2S)-2-benzoylamino- 3-methylbutanohydrazide hydrazones

Abstract

Novel 2-aryl-5-non-substituted / methyl-1,3-thiazolidine-4-one derivatives 14-33 carrying L-valine core were synthesized by the reaction of acylhydrazones 4-13 with thioglycolic acid / thiolactic acid. Structures of all synthesized compounds 14-33 were confirmed by IR, 1H-NMR and HR-MS analysis and 13C-NMR were recorded for selected compounds 17, 21, 28 and 30. None of the compounds 14-33 showed activity against HIV-1 (strain IIIB) or HIV- 2 (strain ROD) in an MT-4/MTT based assay. Compounds 14-33 were also screened against Feline Corona Virus (FIPV), Feline Herpes Virus, HSV-1(KOS), HSV-1 (TK-KOS ACVr), HSV-2 (G), Vaccinia virus, Vesicular stomatitis virus, Cytomegalovirus, Varicella-Zoster virus, Respiratory syncytial virus, Coxsackie B4 virus, Parainfluenza-3 virus, Reovirus-1, Sindbis virus and Punta Toro virus, but none of them showed antiviral activity at subtoxic concentrations. Anti-HCV NS5B RdRp activity of some selected compounds from the series 14-33 were found to vary between 4.1-27 % at the concentration of 100 µM. In vitro antibacterial activity evaluation of selected compounds 16-23 and 25-32, against Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Enterococcus faecalis ATCC 29212, Klebsiella pneumoniae ATCC 4352, Bacillus subtilis ATCC 6633, Staphylococcus epidermidis ATCC 12228, MRSA and antifungal activity against Candida albicans ATCC 10231 resulted in the MIC values between 625->5000 µg/ml.

Keywords

• 4-Thiazolidinones
• L-valine
• antibacterial activity
• anti-HIV activity
• anti-HCV activity.

References

1. [1] Joint United Nations Programme on HIV/AIDS (UNAIDS). Global HIV & AIDS statistics-2020 fact sheet. 2019. www.unaids.org (accessed May 14th, 2021)
2. [2] Bernell SL, Shinogle JA. The relationship between HAART use and employment for HIV-positive individuals: an empirical analysis and policy outlook. Health Policy. 2005; 71(2): 255-264. [CrossRef]
3. [3] Smith RL, de Boer R, Brul S, Budovskaya Y, van Spek H. Premature and accelerated aging: HIV or HAART?. Front Genet. 2013; 3: 328. [CrossRef]
4. [4] Piot P, Abdool Karim SS, Hecht R, Legido-Quigley H, Buse K, Stover J, Resch S, Ryckman T, Møgedal S, Dybul M, Goosby E, Watts C, Kilonzo N, McManus J, Sidibé M. Defeating AIDS--advancing global health. Lancet. 2015;386(9989): 171-218. [CrossRef]
5. [5] De Clercq E. Antiviral drugs in current clinical use. J Clin Virol. 2004; 30(2): 115-133. [CrossRef]
6. [6] De Clercq E. Anti-HIV drugs: 25 compounds approved within 25 years after the discovery of HIV. Int J Antimicrob Agents. 2009; 33(4): 307-320. [CrossRef]
7. [7] Slama L, Li X, Brown T, Jacobson LP, Pialoux G, Macatangay B, Bolan RK, Phair J, Palella FJ Jr. Increases in duration of first highly active antiretroviral therapy over time (1996-2009) and associated factors in the Multicenter AIDS Cohort Study. J Acquir Immune Defic Syndr. 2014; 65(1): 57-64. [CrossRef]
8. [8] Tanaka H, Wada T, Takayama Y, Matsumoto K, Atsuda K, Satoh M. Evaluation of the efficacy and safety of changes in antiretroviral regimens for HIV-infected patients. J Pharm Pharm Sci. 2014; 17(3): 316-323. [CrossRef]

9. [9] Barreca ML, Chimirri A, De Luca L, Monforte AM, Monforte P, Rao A, Zappalà M, Balzarini J, De Clercq E, Pannecouque C, Witvrouw M. Discovery of 2,3-diaryl-1,3-thiazolidin-4-ones as potent anti-HIV-1 agents. Bioorg Med Chem Lett. 2001; 11(13): 1793-1796. [CrossRef]
10. [10] Rao A, Balzarini J, Carbone A, Chimirri A, De Clercq E, Monforte AM, Monforte P, Pannecouque C, Zappalà M. 2-(2,6-Dihalophenyl)-3-(pyrimidin-2-yl)-1,3-thiazolidin-4-ones as non-nucleoside HIV-1 reverse transcriptase inhibitors. Antiviral Res. 2004; 63(2): 79-84. [CrossRef]
11. [11] Balzarini J, Orzeszko B, Maurin JK, Orzeszko A. Synthesis and anti-HIV studies of 2-adamantyl-substituted thiazolidin-4-ones. Eur J Med Chem. 2007; 42(7): 993-1003. [CrossRef]
12. [12] Balzarini J, Orzeszko-Krzesińska B, Maurin JK, Orzeszko A. Synthesis and anti-HIV studies of 2- and 3-adamantyl-substituted thiazolidin-4-ones. Eur J Med Chem. 2009; 44(1): 303-311. [CrossRef]
13. [13] Murugesan V, Makwana N, Suryawanshi R, Saxena R, Tripathi R, Paranjape R, Kulkarni S, Katti SB. Rational design and synthesis of novel thiazolidin-4-ones as non-nucleoside HIV-1 reverse transcriptase inhibitors. Bioorg Med Chem. 2014; 22(12): 3159-3170. [CrossRef]
14. [14] Rawal RK, Prabhakar YS, Katti SB, De Clercq E. 2-(Aryl)-3-furan-2-ylmethyl-thiazolidin-4-ones as selective HIV-RT inhibitors. Bioorg Med Chem. 2005; 13(24): 6771-6776. [CrossRef]
15. [15] Rawal RK, Tripathi R, Katti SB, Pannecouque C, De Clercq E. Design, synthesis, and evaluation of 2-aryl-3-heteroaryl-1,3-thiazolidin-4-ones as anti-HIV agents. Bioorg Med Chem. 2007; 15(4): 1725-1731. [CrossRef]
16. [16] Rawal RK, Tripathi R, Katti SB, Pannecouque C, De Clercq E. Synthesis and evaluation of 2-(2,6-dihalophenyl)-3-pyrimidinyl-1,3-thiazolidin-4-one analogues as anti-HIV-1 agents. Bioorg Med Chem. 2007; 15(9): 3134-3142. [CrossRef]
17. [17] Rawal RK, Tripathi RK, Katti SB, Pannecouque C, De Clercq E. Synthesis and biological evaluation of 2,3-diaryl substituted-1,3-thiazolidin-4-ones as anti-HIV agents. Med Chem. 2007; 3(4): 355-363. [CrossRef]
18. [18] Rawal RK, Tripathi R, Katti SB, Pannecouque C, De Clercq E. Design and synthesis of 2-(2,6-dibromophenyl)-3-heteroaryl-1,3-thiazolidin-4-ones as anti-HIV agents. Eur J Med Chem. 2008; 43(12): 2800-2806. [CrossRef]
19. [19] Rawal RK, Tripathi R, Kulkarni S, Paranjape R, Katti SB, Pannecouque C, De Clercq E. 2-(2,6-Dihalo-phenyl)-3-heteroaryl-2-ylmethyl-1, 3-thiazolidin-4-ones: anti-HIV agents. Chem Biol Drug Des. 2008; 72(2): 147-154. [CrossRef]
20. [20] Suryawanshi R, Jadhav S, Makwana N, Desai D, Chaturbhuj D, Sonawani A, Idicula-Thomas S, Murugesan V, Katti SB, Tripathy S, Paranjape R, Kulkarni S. Evaluation of 4-thiazolidinone derivatives as potential reverse transcriptase inhibitors against HIV-1 drug resistant strains. Bioorg Chem. 2017; 71: 211-218. [CrossRef]
21. [21] Gupta A, Swaminathan G, Martin-Garcia J, Navas-Martin S. MicroRNAs, hepatitis C virus, and HCV/HIV-1 co-infection: new insights in pathogenesis and therapy. Viruses. 2012; 4(11): 2485-2513. [CrossRef]
22. [22] Grebely J, Tyndall MW. Management of HCV and HIV infections among people who inject drugs. Curr Opin HIV AIDS. 2011; 6(6): 501-507. [CrossRef]
23. [23] Alter MJ. Epidemiology of viral hepatitis and HIV co-infection. J Hepatol. 2006;44(1 Suppl):S6-S9. [CrossRef]
24. [24] Kaminskyy D, Kryshchyshyn A, Lesyk R. 5-Ene-4-thiazolidinones - An efficient tool in medicinal chemistry. Eur J Med Chem. 2017; 140: 542-594. [CrossRef]
25. [25] Rawal RK, Katti SB, Kaushik-Basu N, Arora P, Pan Z. Non-nucleoside inhibitors of the hepatitis C virus NS5B RNA-dependant RNA polymerase: 2-aryl-3-heteroaryl-1,3-thiazolidin-4-one derivatives. Bioorg Med Chem Lett. 2008;18(23): 6110-6114. [CrossRef]
26. [26] Küçükgüzel G, Kocatepe A, De Clercq E, Sahin F, Güllüce M. Synthesis and biological activity of 4-thiazolidinones, thiosemicarbazides derived from diflunisal hydrazide. Eur J Med Chem. 2006; 41(3): 353-359. [CrossRef]
27. [27] Kaushik-Basu N, Bopda-Waffo A, Talele TT, Basu A, Chen Y, Kucukguzel SG. 4-Thiazolidinones: a novel class of hepatitis C virus NS5B polymerase inhibitors. Front Biosci. 2008; 13: 3857-3868.
28. [28] Küçükgüzel İ, Satılmış G, Gurukumar KR, Basu A, Tatar E, Nichols DB, Talele TT, Kaushik-Basu N. 2-Heteroarylimino-5-arylidene-4-thiazolidinones as a new class of non-nucleoside inhibitors of HCV NS5B polymerase. Eur J Med Chem. 2013;69:931-941. [CrossRef]
29. [29] Çakır G, Küçükgüzel İ, Guhamazumder R, Tatar E, Manvar D, Basu A, Patel BA, Zia J, Talele TT, Kaushik-Basu N. Novel 4-thiazolidinones as non-nucleoside inhibitors of hepatitis C virus NS5B RNA-dependent RNA polymerase. Arch Pharm (Weinheim). 2015; 348(1): 10-22. [CrossRef]
30. [30] Lemm JA, O'Boyle D 2nd, Liu M, Nower PT, Colonno R, Deshpande MS, Snyder LB, Martin SW, St Laurent DR, Serrano-Wu MH, Romine JL, Meanwell NA, Gao M. Identification of hepatitis C virus NS5A inhibitors. J Virol. 2010;84(1): 482-91. [CrossRef]
31. [31] Huson MA, Grobusch MP, van der Poll T. The effect of HIV infection on the host response to bacterial sepsis. Lancet Infect Dis. 2015; 15(1): 95-108. [CrossRef]
32. [32] Martinson NA, Hoffmann CJ, Chaisson RE. Epidemiology of tuberculosis and HIV: recent advances in understanding and responses. Proc Am Thorac Soc. 2011; 8(3): 288-293. [CrossRef]
33. [33] Hernández JC, Arteaga J, Paul S, Kumar A, Latz E, Urcuqui-Inchima S. Up-regulation of TLR2 and TLR4 in dendritic cells in response to HIV type 1 and coinfection with opportunistic pathogens. AIDS Res Hum Retroviruses. 2011;27(10): 1099-1109. [CrossRef]
34. [34] Tatar E, Küçükgüzel İ, De Clercq E, Krishnan R, Kaushik-Basu N. Synthesis, characterization and antiviral evaluation of 1,3-Thiazolidine-4-one derivatives bearing L-Valine side chain. Marmara Pharm J. 2012; 16(3): 181-193. [CrossRef]
35. [35] Tatar E, Küçükgüzel İ, Daelemans D, Talele TT, Kaushik-Basu N, De Clercq E, Pannecouque C. Some hydrazones of 2-aroylamino-3-methylbutanohydrazide: synthesis, molecular modeling studies, and identification as stereoselective inhibitors of HIV-1. Arch Pharm (Weinheim). 2013; 346(2): 140-153. [CrossRef]
36. [36] Joshi P, Anderson C, Binch H, Hadida S, Yoo S, Bergeron D, Decker C, terHaar E, Moore J, Garcia-Guzman M, Termin A. Identification of potent CNS-penetrant thiazolidinones as novel CGRP receptor antagonists. Bioorg Med Chem Lett. 2014; 24(3): 845-849. [CrossRef]
37. [37] Gawande SS, Warangkar SC, Bandgar BP, Khobragade CN. Synthesis of new heterocyclic hybrids based on pyrazole and thiazolidinone scaffolds as potent inhibitors of tyrosinase. Bioorg Med Chem. 2013; 21(10): 2772-2777. [CrossRef]
38. [38] Cihan-Üstündağ G, Şatana D, Özhan G, Çapan G. Indole-based hydrazide-hydrazones and 4-thiazolidinones: synthesis and evaluation as antitubercular and anticancer agents. J Enzyme Inhib Med Chem. 2016; 31(3): 369-380. [CrossRef]
39. [39] Wrobel J, Jetter J, Kao W, Rogers J, Di L, Chi J, Peréz MC, Chen GC, Shen ES. 5-Alkylated thiazolidinones as follicle-stimulating hormone (FSH) receptor agonists. Bioorg Med Chem. 2006; 14(16): 5729-5741. [CrossRef]
40. [40] Ünsal-Tan O, Özadalı K, Pişkin K, Balkan A. Molecular modeling, synthesis and screening of some new 4-thiazolidinone derivatives with promising selective COX-2 inhibitory activity. Eur J Med Chem. 2012; 57: 59-64. [CrossRef]