Synthesis, Biological Evaluation and Molecular Docking of Certain Sulfones as Potential Nonazole Antifungal Agents

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Mohamed FaresHatem A Abdel-Aziz

Abstract

We reported herein the synthesis, antifungal activity, docking and in silico ADME prediction studies of four novel series of sulfones 6a-f, 8a-c, 10a-f and 12a-c. All the newly synthesized sulfones were tested against four strains of Candida (including fluconazole-resistant Candida), two strains of Aspergillus, two dermatophytic fungi (Trichophytons mentagrophyte and Microsporum canis) and Syncephalastrum sp. with fluconazole as a reference drug. In general, compounds 8a and 10b showed selective and potent anticandidal activity (MIC: 0.19-0.81 µM) relative to fluconazole (MIC = 1.00 µM). Furthermore, 10e and 12a elicited a remarkable and selective antifungal activity against Aspergillus sp. and the dermatophytic fungi (MIC: 0.16-0.79 µM) relative to fluconazole (MIC: 2-2.6 µM). Moreover, the docking results of the sulfones 6a, 8a, 10a and 10b at the active site of CYT P450 14α-sterol demethylase showed a comparable binding interaction (interaction Energy = -34.87 to -42.43 kcal/mol) with that of fluconazole (IE = -40.37 kcal/mol).

References

Jul 4, 1990·Journal of the National Cancer Institute·P SkehanM R Boyd
Jan 9, 1999·Clinical Microbiology Reviews·D J SheehanC M Sibley
Mar 15, 2001·Proceedings of the National Academy of Sciences of the United States of America·L M PodustM R Waterman
Jun 16, 2001·Antimicrobial Agents and Chemotherapy·I Orme, UNKNOWN Tuberculosis Drug Screening Program
Feb 19, 2002·Antimicrobial Agents and Chemotherapy·K V ClemonsD A Stevens
Aug 13, 2004·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Hilmar WisplinghoffMichael B Edmond
Jan 16, 2007·Clinical Microbiology Reviews·M A Pfaller, D J Diekema
Feb 27, 2007·European Journal of Medicinal Chemistry·C CurtiP Vanelle
Sep 29, 2007·Journal of Medicinal Chemistry·Bin YaoHui Tang
Oct 27, 2007·International Journal of Antimicrobial Agents·Pei-Lan ShaoPo-Ren Hsueh
Jan 4, 2008·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Zeina A Kanafani, John R Perfect
Sep 29, 2009·European Journal of Medicinal Chemistry·Hatem A Abdel-Aziz, Amal A I Mekawey
Aug 2, 2011·Mayo Clinic Proceedings·Russell E Lewis
Jul 4, 2012·European Journal of Medicinal Chemistry·A MuralikrishnaN Siva Krishna
Aug 21, 2012·Bioorganic & Medicinal Chemistry·Muthu K KathiravanSandeep Gadhwe
Dec 4, 2012·European Journal of Medicinal Chemistry·Naveen Kumar KonduruNaseem Ahmed
Nov 21, 2013·The Lancet Infectious Diseases·Ramanan LaxminarayanOtto Cars
Mar 19, 2014·Mycoses·Shabnam ShafieeIradj Ashrafi Tamai
Apr 24, 2015·International Journal of Molecular Sciences·Hatem A Abdel-AzizDalia H Soliman
Jul 15, 2015·Biological & Pharmaceutical Bulletin·Hatem Abdel-Kader Abdel-AzizDalia Hussein Soliman

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Citations

May 24, 2018·Future Medicinal Chemistry·Mahmoud F Abo-AshourNagwa M Abdel Gawad
Sep 25, 2018·Mini Reviews in Medicinal Chemistry·Małgorzata GizińskaZbigniew Ochal
Nov 3, 2017·Biological & Pharmaceutical Bulletin·Dalia Hussein SolimanHatem Abdel-Kader Abdel-Aziz
Jun 14, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mohamed El-NaggarHatem A Abdel-Aziz
Sep 21, 2020·Journal of Molecular Modeling·Jamelah S Al-OtaibiC Van Alsenoy

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Methods Mentioned

BETA
X-ray
NMR
ELISA

Software Mentioned

Graph Pad Prism
Discovery Studio
CHARMM
CDOCKER
GraphPad

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