Synthesis, antimicrobial evaluation and in silico studies of novel 3,4-disubstituted pyrrolidinesulfonamides

Keywords: pyrrolidinesulfonamides, synthesis, in silico studies, β-glucosidase, antimicrobial activity

Abstract

3,4-Disubstituted pyrrolidinesulfonamides were synthesized and screened for their antimicrobial activity. Title compounds were established as potent antibacterial and antifungal agents. Noteworthy antimicrobial activity was found for the title compounds against the tested microorganisms. They exhibit comparable results with standard drugs. Besides the in vitro antimicrobial activity, the synthesized compounds were evaluated for their in silico inhibitory activity on active site of β-glucosidase enzyme. In silico studies were done by GOLD docking method against β-glucosidase 3VKK (PDB Id). In silico studies were conducted to evaluate the ability of synthesized compounds to inhibit the β-glucosidase enzyme. The results revealed that 3,4-disubstitutedpyrrolidinesulfonamides are the potent β-glucosidase inhibitors by binding at the active site. A sensible inhibition against β-glucosidases was observed for the compound with 13,4-oxadizole ring has higher β-glucosidase inhibition activity than the other compounds. The free energy of binding and inhibition constant (Ki) of the docked compounds were evaluated and presented.

References

1 Denmark SE, Marcin LR (1995) J Org Chem 60:3221-3235. Crossref

2 Blum A, Diederich WE (2009) Curr Org Synth 6:38-53. Crossref

3 Najera C, Sansano JM (2013) Recherche et développement Grand prix SCF January 370

4 Hensler ME, Bernstein G, Nizet V, Nefzib A (2006) Bioorg Med Chem Lett 16(19):5073-5079. Crossref

5 (2006) Patent US7115639 B2 Pyrrolidineoxadiazole- and thiadiazole oxime derivatives being oxytocin receptor antagonists: Schwarz M, Quattropani A, Page P, Thomas RJ, Pomel V.

6 Sharma R, Soman SS (2015) Eur J Med Chem 90:342-350. Crossref

7 Supuran CT, Casini A, Scozzafava A (2003) Med Res Rev 23(5):535-558. Crossref

8 Roush WR, Gwaltney SL, Cheng J, Scheidt KA, McKerrow GH, Hansell E (1998) J Am Chem Soc 120(42)10994-10995. Crossref

9 Thaisrivongs S, Skulnick HI, Turner SR, Strohbach JW, Tommasi RA, et al (1996) J Med Chem 39(22)4349-4353. Crossref

10 Supuran CT, Casini A, Scozzafava A (2003) Med Res Rev 23(5):535-558. Crossref

11 Koyanagi N, Nagasu T, Fujita F (1994) Cancer Res 1(54)1702-1706.

12 Werner LH, Habicht E, Zergenyi J (1978) Sulfonamide diuretics in Diuretic agents (ed. by Cragoe EJ). American Chemical Society, Washington, DC. P.38-55.

13 Yin Z, Zhang W, Feng F, Zhang Y, Kang W (2014) Food Science and Human Wellness 3(3-4)136-174. Crossref

14 Supuran CT, Innocenti A, Mastrolorenzo A, Scozzafava A (2004) Mini-Reviews in Medicinal Chemistry 4(2)189-200. Crossref

15 Blass BE, Iyer P, Abou-Gharbia M, Childers WE, Gordon JC, et al (2016) Bioorg Med Chem Lett 26(23)5825-5829. Crossref

16 Sánchez-Medina A, Garcia-Sosa K, May-Pat F, Pea-Rodríguez LM (2001) Phytomedicine 8(2):144-151. Crossref

17 De Melo EB, Gomes AS, Carvalho I (2006) Tetrahedron 62(44)10277-10302. Crossref

18 Cheng AYY, Josse RG (2004) Drug Discov Today: Therapeutic Strategies 1(2)201-206. Crossref

19 Von Geldern TV, Tasker AS, Sorensen BK, Winn M, Szczepankiewicz BG, et al (1999) J Med Chem 42(18):3668-3678. Crossref

20 Papandréou MJ, Barbouche R, Guieu R, Kieny MP, Fenouillet E (2002) Mol Pharmacol 61(1):186-193. Crossref

21 Nishimura Y (2003) Curr Top Med Chem 3(5):575-591. Crossref

22 Santosh Kumar B, Raghavendra Guru Prasad A, Madhu G, Raveendra Reddy P, Ravindranath LK (2014) Ann Pharm Fr 72:256-266. Crossref

23 Da Silva ET, Fona FS, Lima ELS (2004) J Braz Chem Soc 15(3):433-436. Crossref

24 Chen HH, Gross S, Liao J, McLaughlin M, Dean T, Sly WS, May JA (2000) Bioorg Med Chem 8: 957-975. Crossref

25 Santosh Kumar B, Madhu G, Raveendra Reddy P, Ravindranath LK (2012) Der Chemical Sinica 3(5):1124-1134.

26 Hui A, Zhang J, Sun H, Wang Z (2008) ARKIVOC (ii)25-32.

27 Lysek R, Vogel P (2004) Helv Chim Acta 87(12)3167-3181. Crossref

28 Popowycz F, Gerber-Lemaire S, Schutz C, Vogel P (2004) Helv Chim Acta 87(4)800-180. Crossref
Published
2019-12-09
How to Cite
Santosh Kumar, B., Madhu, G., & Ravindranath, L. (2019). Synthesis, antimicrobial evaluation and in silico studies of novel 3,4-disubstituted pyrrolidinesulfonamides. Chemical Bulletin of Kazakh National University, 95(4), 28-40. https://doi.org/https://doi.org/10.15328/cb1044