Synthesis, Characterization and Biological Activities of Novel Chiral Bis 1,2-diolcarbothioamides

Abstract

2,2'-[(2R,3R)-2,3-dihydroxy-1,4-dioxobutane-1,4-diyl]bis(N-aryl-alkylhydrazine-1-carbothioamide (T1–5) were obtained by the interaction of (2R,3R)-2,3-dihydroxybutanedihydrazide (1) with five different isothiocyanate alkyl(aryl) derivatives. The structures of the final compounds were confirmed by elemental analyses, FT-IR, ¹H-NMR and ¹³C-NMR. The antioxidant, antimicrobial and anticancer properties of the synthesized compounds were also investigated. Three of the triazole derivatives with p-tolyl, benzyl and phenyl substituents (T3–5) displayed good antioxidant and anticancer activity in comparison to the standards.

Keywords

• Carbothioamide
• anticancer
• antioxidant
• antimicrobial

References

1. Shekarchi M, Pirali-Hamedani M, Navidpour L, Adib N, Shafiee A. Synthesis, antibacterial and antifungal activities of 3-aryl-5-(pyridin-3-yl)-4,5-dihydropyrazole-1-carbothioamide derivatives. Journal of the Iranian Chemical Society. 5: 150–158.
2. Chernovyants M, Aleshina N. 2012. Study on the antioxidant activity and quantification of thioamides based on nitrogen five-membered heterocycles by the kinetic technique. Journal of Analytical Chemistry. 67: 214–218.
3. Corban GJ, Hadjikakou SK, Tsipis AC, Kubicki M, Bakas T, Hadjiliadis N. Inhibition of peroxidase-catalyzed iodination by thioamides: experimental and theoretical study of the antithyroid activity of thioamides. New Journal of Chemistry. 35: 213–224.
4. Kulandasamy R, Adhikari AV, Stables JP. 2010. Design and synthesis of new Amides and Thioamides derived from 3,4-ethylenedioxythiophene as potential anticonvulsants. Bulletin of the Korean Chemical Society. 31: 3318–3326.
5. Ravez S, Corbet C, Spillier Q, Dutu A, Robin AD, Mullarky E, Cantley LC, Feron O, Frédérick R. α-Ketothioamide derivatives: a promising tool to interrogate phosphoglycerate dehydrogenase (PHGDH). Journal of Medicinal Chemistry. 60: 1591–1597.
6. Jagodziński TS. 2003. Thioamides as useful synthons in the synthesis of heterocycles. Chemical Reviews. 103: 197–228.
7. Dyachenko VD, Dyachenko IV, Nenajdenko VG. 2018. Cyanothioacetamide: a polyfunctional reagent with broad synthetic utility. Russian Chemical Reviews. 87: 1–27.
8. Yoshimura A, Todora AD, Kastern BJ, Koski SR, Zhdankin VV. 2014. Synthesis of 1,2,4‐thiadiazoles by oxidative dimerization of carbothioamides by using oxone. European Journal of Organic Chemistry. 2014: 5149–5152.

9. Belskaia NP, Deryabina TG, Koksharov AV, Kodess MI, Dehaen W, Lebedev AT, Bakulev VA. 2007. A novel approach to fused 1,2,4-triazines by intramolecular cyclization of 1,2-diaza-1,3-butadienes bearing allyl (propargyl) sulfanyl and cyclic tert-amino groups. Tetrahedron Letters. 48: 9128–9131.
10. Bakulev V, Shafran Y, Dehaen W. 2019. Progress in intermolecular and intramolecular reactions of thioamides with diazo compounds and azides. Tetrahedron Letters. 60: 513–523.
11. Bergman J, Pettersson B, Hasimbegovic V, Svensson PH. 2011. Thionations using a P4S10−pyridine complex in solvents such as acetonitrile and dimethyl sulfone. The Journal of Organic Chemistry. 76: 1546–1553.
12. Kurina‐Sanz M, Bisogno FR, Lavandera I, Orden AA, Gotor V. 2009. Promiscuous substrate binding explains the enzymatic stereo‐and regiocontrolled synthesis of enantiopure hydroxy ketones and diols. Advanced Synthesis & Catalysis. 351: 1842–1848.
13. Leung D, Abbenante G, Fairlie DP. 2000. Protease inhibitors: current status and future prospects. Journal of Medicinal Chemistry. 43: 305–341.
14. Wright AE, Schäfer M, Midland S, Munnecke DE, Sims JJ. 1989. Lateral root inducing compounds from the bacterium Erwinia quercina: Isolation, structure and synthesis. Tetrahedron Letters. 30: 5699–5702.
15. Kolb HC, Sharpless KB. 1992. A simplified procedure for the stereospecific transformation of 1,2-diols into epoxides. Tetrahedron. 48: 10515–10530.
16. Nicolaou K, Huang X, Snyder SA, Rao PB, Bella M, Reddy MV. 2002. A novel regio‐and stereoselective synthesis of sulfamidates from 1,2‐diols using burgess and related reagents: A facile entry into β‐amino alcohols. Angewandte Chemie. 114: 862–866.
17. Bianchi D, Bosetti A, Cesti P, Golini P. 1992. Enzymatic resolution of 1,2-diols: preparation of optically pure dropropizine. Tetrahedron Letters. 33: 3231–3234.
18. Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice-Evans C. 1999. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radical Biology and Medicine. 26: 1231–1237.
19. Halliwell B, Gutteridge JMC, Aruoma O. 1987. The deoxyribose method: a simple test tube assay for determination of rate constants for reactions of hydroxyl radicals. Analytical Biochemistry. 165: 215–219.
20. Brand-Williams W, Cuvelier ME, Berset C. 1995. Use of a free radical method to evaluate antioxidant activity. LWT-Food Science and Technology. 28: 25–30.
21. Keser S. 2014. Antiradical activities and phytochemical compounds of firethorn (Pyracantha coccinea) fruit extracts. Natural Product Research. 28: 1789–1794.
22. Keser S, Keser F, Kaygili O, Tekin S, Demir E, Turkoglu I, Turkoglu S, Parlak AE, Yilmaz O, Karatepe M, Sandal S, Kirbag S. 2020. Phytochemical compounds and antiradical, antimicrobial, and cytotoxic activities of the extracts from Hypericum scabrum L. flowers. Natural Product Research. 34: 714–719.
23. Keser S, Keser F, Karatepe M, Kaygili O, Tekin S, Turkoglu I, Demir E, Yilmaz O, Kirbag S, Sandal, S. 2020. Bioactive contents, in vitro antiradical, antimicrobial and cytotoxic properties of rhubarb (Rheum ribes L.) extracts. Natural Product Research. 34: 3353–3357.
24. Keser S, Kak O. 2021. In vitro antimicrobial, antiradical, anticancer evaluation, and phytochemical contents of endemic Scorzonera semicana DC. Journal of Food Processing and Preservation. 45: e15971.
25. Hamza A, Zouari N. Zouari S, Jdir H, Zaidi S, Gtari M, Neffati M. 2016. Nutraceutical potential, antioxidant and antibacterial activities of Terfezia boudieri Chatin, a wild edible desert truffle from Tunisia arid zone. Arabian Journal of Chemistry. 9: 383–389.
26. Matysiak J, Opolski A. 2006. Synthesis and antiproliferative activity of N-substituted 2-amino-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazoles. Bioorganic&Medicinal Chemistry. 14: 4483–4489.
27. Rzeski W, Matysiak J, Kandefer-Szerszeń M. 2007. Anticancer, neuroprotective activities and computational studies of 2-amino-1,3,4-thiadiazole based compound. Bioorganic & Medicinal Chemistry. 15: 3201–3207.
28. Wei MX, Feng L, Li XQ, Zhou XZ, Shao ZH. 2009. Synthesis of new chiral 2,5-disubstituted 1,3,4-thiadiazoles possessing γ-butenolide moiety and preliminary evaluation of in vitro anticancer activity. European Journal of Medicinal Chemistry. 44: 3340–3344.
29. Swamy SN, Priya B, Prabhuswamy B, Doreswamy B, Prasad JS, Rangappa KS. 2006. Synthesis of pharmaceutically important condensed heterocyclic 4,6-disubstituted-1,2,4-triazolo-1,3,4-thiadiazole derivatives as antimicrobials. European Journal of Medicinal Chemistry. 41: 531–538.
30. Mirzaei J. Siavoshi F, Emami S, Safari F, Khoshayand MR. Shafiee A, Foroumadi A. 2008. Synthesis and in vitro anti-Helicobacter pylori activity of N-[5-(5-nitro-2-heteroaryl)-1,3,4-thiadiazol-2-yl] thiomorpholines and related compounds. European Journal of Medicinal Chemistry. 43: 1575–1580.
31. Karatepe A, Çetin A. 2020. Antioxidant and prooxidant activity of new 1,2-diols and thiadiazoles derivatives in Saccharomyces cerevisiae yeast cells. Cumhuriyet Science Journal. 41: 712–719.
32. Husain A, Rashid M, Shaharyar M, Siddiqui AA, Mishra R. 2013. Benzimidazole clubbed with triazolo-thiadiazoles and triazolo-thiadiazines: New anticancer agents. European Journal of Medicinal Chemistry. 62: 785–798.
33. McClements DJ, Decker EA. 2000. Lipid oxidation in oil‐in‐water emulsions: Impact of molecular environment on chemical reactions in heterogeneous food systems. Journal of Food Science. 65: 1270–1282.