DESIGN, SYNTHESIS AND MOLECULAR DOCKING STUDY OF HYBRID QUINOLINE-4-YL-OXADIAZOLES/OXATHIADIAZOLES AS POTENT ANTIFUNGAL AGENTS

Authors

  • Firoz A. Kalam Khan Y. B. Chavan College of Pharmac
  • Jaiprakash N. Sangshetti Associate Professor Y.B.Chavan College of Pharmacy Aurangabad-431001(MS) INDIA

Keywords:

Quinoline, Oxadiazole, Oxathiadiazole, Antifungal activity, Molecular docking study, Nil

Abstract

Objective: The aim of the present work was to design and synthesize hybrid quinoline-4-yl-oxadiazoles/oxathiadiazole derivatives and evaluate them for in vitro antifungal activity against human disease causing pathogens.

Methods: The compounds 5(a-d), 6(a-d) and 7(a-d) were efficiently synthesized in good yields. The synthesized compounds were characterized using 1H NMR, 13C NMR and Mass spectra. The synthesized compounds were screened for in vitro antifungal activity and minimum inhibitory concentration (MIC) values were determined using standard agar method. Molecular docking study was performed against fungal enzyme P450 cytochrome lanosterol 14α-demethylase using VLife MDS 4.3 software.

Results: The synthesized compounds had shown good to moderate in vitro antifungal activity. The compound 6a (MIC range = 15-25 µg/ml) from 1,2,3,5-oxathiadiazole-2-oxide series showed most potent activity amongst the synthesized compounds when compared with standard clotrimazole (MIC range = 12.5-25 µg/ml). The molecular docking study of synthesized compounds showed good binding interactions against active site of fungal enzyme P450 cytochrome lanosterol 14α-demethylase.

Conclusion: The results of in vitro antifungal activity and molecular docking study revealed that the synthesized compounds have potential antifungal activity and can be further optimized and developed as a lead compound.

 

Downloads

Download data is not yet available.

References

Gilks CF. Acute bacterial infections and HIV disease. Br Med Bull 1998;54:383-93.

Samaras V, Rafailidis PI, Mourtzoukou EG, Peppas G, Falagas ME. Chronic bacterial and parasitic infections and cancer: a review. J Infect Dev Ctries 2010;4:267-81.

Shoham S, Marr KA. Invasive fungal infections in solid organ transplant recipients. Future Microbiol 2012;7:639-55.

WHO, World Health Organization. Available from: http://www.who.int/en/.

Thompson GR, Cadena J, Patterson TF. Overview of antifungal agents. Clin Chest Med 2009;30:203-15.

Kanafani ZA, Perfect JR. Antimicrobial resistance: resistance to antifungal agents: mechanisms and clinical impact. Clin Infect Dis 2008;46:120-8.

Rigler SM, Greathouse GA. Fungicidal potency of quinoline homologues and derivatives. Indian Eng Chem Res 1941;33:693-4.

Mason CL. A study of the fungicidal action of 8-hydroksyquinolinol and some of its derivatives. Phytopathol 1948;38:740-51.

Gershon H, Gershon M, Clarke DD. Antifungal activity of substituted 8-quinolinol-5-and 7-sulfonic acids: a mechanism of action is suggested based on intramolecular synergism. Mycopathologia 2001;155:213-7.

Jain M, Khan SI, Tekwani BL, Jacob MR, Singh S, Singh PP, et al. Synthesis, antimalarial, antileishmanial and antimicrobial activities of some 8-quinolinamine analogues. Bioorg Med Chem 2005;13:4458-66.

Sangshetti JN, Nagawade RR, Shinde DB. Synthesis of novel 3-(1-(1-substituted piperidin-4-yl)-1h-1,2,3-triazol-4-yl)-1,2,4-oxadiazol-5(4h)-one as antifungal agents. Bioorg Med Chem Lett 2009;19:3564–7.

Sangshetti JN, Shinde DB. Synthesis of some novel 3-(1-(1-substitutedpiperidin-4-yl)-1h-1,2,3-triazol-4-yl)-5-substituted phenyl-1,2,4-oxadiazoles as antifungal agents. Eur J Med Chem 2011;46:1040-4.

Sangshetti JN, Shinde DB. Synthesis and SAR of some new 4-substituted 3h-1,2,3,5-oxathiadiazole-2-oxides as antifungal agents. Lett Drug Des Discov 2010;7:171-5.

Sangshetti JN, Shinde DB. One pot synthesis and SAR of some novel 3-substituted-5,6-diphenyl-1,2,4-triazines as antifungal agents. Bioorg Med Chem Lett 2010;20:742-45.

(b) Sangshetti JN, Dharmadhikari PP, Chouthe RS, Fatema B, Lad V, Karande V, et al. Microwave assisted nano (ZnO–TiO2) catalyzed synthesis of some new 4,5,6,7-tetrahydro-6-((5-substituted-1,3,4-oxadiazol-2-yl)methyl)thieno[2,3-c]pyridine as antimicrobial agents. Bioorg Med Chem Lett 2013;23:2250-3.

(c) Sangshetti JN, Lokwani DK, Sarkate AP, Shinde DB. Synthesis, antifungal activity, and docking study of some new 1,2,4-triazole analogs. Chem Biol Drug Des 2011;78:800-09.

Sangshetti JN, Chabukswar AR, Shinde DB. Microwave assisted one pot synthesis of some novel 2,5-disubstituted-1,3,4-oxadiazoles as antifungal agents. Bioorg Med Chem Lett 2011;21:444-8.

(b) Sangshetti JN, Shaikh RI, Khan FAK, Patil RH, Marathe SD, Gade WN, et al. Synthesis, antileishmanial activity and docking study of n′-substitutedbenzylidene-2-(6,7-dihydrothieno[3,2-c]pyridin-5(4h)-yl)acetohydrazides. Bioorg Med Chem Lett 2014;24:1605-10.

(c) Sangshetti JN, Khan FAK, Chouthe RS, Damale MG, Shinde DB. Synthesis, Docking and ADMET prediction of novel 5-((5-substituted-1-H-1,2,4-triazol-3-yl)methyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine as antifungal agents. Chinese Chem Lett 2014;25:1033-8.

Sandra G, Giuseppe C, Stefania B, Gagan K, Salvatore SC. Clotrimazole scaffold as an innovative pharmacophore towards potent antimalarial agents: design, synthesis, and biological and structure-activity relationship studies. J Med Chem 2008;51:1278–94.

Greenwood D. In: Medical Microbiology.14th edn. London: ELBS; 1992. p. 1.

Halgren TA. Merck molecular force field I. basis, form, scope, parameterization, and performance of MMFF94. J Comput Chem 1996;17:490-19.

Hooft RW, Vriend G, Sander C, Abola EE. Errors in protein structures. Nat 1996;381:272.

VLife Molecular Design Suite 4.3, VLife Sciences Technologies Pvt. Ltd. Available from: www.Vlifesciences.com.

Published

01-04-2015

How to Cite

Khan, F. A. K., and J. N. Sangshetti. “DESIGN, SYNTHESIS AND MOLECULAR DOCKING STUDY OF HYBRID QUINOLINE-4-YL-OXADIAZOLES/OXATHIADIAZOLES AS POTENT ANTIFUNGAL AGENTS”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 7, no. 4, Apr. 2015, pp. 223-9, https://mail.innovareacademics.in/journals/index.php/ijpps/article/view/4684.

Issue

Section

Original Article(s)