title: Synthesis, Biological Evaluation and Molecular Docking of Certain Sulfones as Potential Nonazole Antifungal Agents.
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).
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo 11829, Egypt. ph.fares@yahoo.com.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Fares
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo 11829, Egypt. madyyy_@hotmail.com.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Said
authors.affiliation: Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, Egypt. muhammad.alsherbiny@pharma.cu.edu.eg.
authors.forename: Muhammad A
authors.initials: MA
authors.lastname: Alsherbiny
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo 11829, Egypt. radwa.eladwy22@gmail.com.
authors.forename: Radwa A
authors.initials: RA
authors.lastname: Eladwy
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo 11829, Egypt. hadia.almahli@yahoo.com.
authors.forename: Hadia
authors.initials: H
authors.lastname: Almahli
authors.affiliation: The Regional Center for Mycology and Biotechnology, Al-Azhar University, Cairo 11759, Egypt. marwa2rcmb@yahoo.com.
authors.forename: Marwa M
authors.initials: MM
authors.lastname: Abdel-Aziz
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P. O. Box 2457, Riyadh 11451, Saudi Arabia. ghabbourh@yahoo.com.|Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. ghabbourh@yahoo.com.
authors.forename: Hazem A
authors.initials: HA
authors.lastname: Ghabbour
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo 11829, Egypt. wagdy2000@gmail.com.
authors.forename: Wagdy M
authors.initials: WM
authors.lastname: Eldehna
authors.affiliation: Department of Applied Organic Chemistry, National Research Center, Dokki, Giza 12622, Egypt. hatem_741@yahoo.com.
authors.forename: Hatem A
authors.initials: HA
authors.lastname: Abdel-Aziz
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001393:Azoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D015725:Fluconazole / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D066244:Proton Magnetic Resonance Spectroscopy; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D001393:Azoles; D013450:Sulfones; D015725:Fluconazole
keywords: anticandidal; antifungal; docking; sulfone; synthesis