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Molecules. 2016 Jan 20;21(1):E114. doi: 10.3390/molecules21010114.

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

Author information

1
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo 11829, Egypt. ph.fares@yahoo.com.
2
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo 11829, Egypt. madyyy_@hotmail.com.
3
Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, Egypt. muhammad.alsherbiny@pharma.cu.edu.eg.
4
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo 11829, Egypt. radwa.eladwy22@gmail.com.
5
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo 11829, Egypt. hadia.almahli@yahoo.com.
6
The Regional Center for Mycology and Biotechnology, Al-Azhar University, Cairo 11759, Egypt. marwa2rcmb@yahoo.com.
7
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P. O. Box 2457, Riyadh 11451, Saudi Arabia. ghabbourh@yahoo.com.
8
Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. ghabbourh@yahoo.com.
9
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo 11829, Egypt. wagdy2000@gmail.com.
10
Department of Applied Organic Chemistry, National Research Center, Dokki, Giza 12622, Egypt. hatem_741@yahoo.com.

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).

KEYWORDS:

anticandidal; antifungal; docking; sulfone; synthesis

PMID:
26805791
DOI:
10.3390/molecules21010114
[Indexed for MEDLINE]
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