{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T03:20:05Z","timestamp":1780456805742,"version":"3.54.1"},"reference-count":35,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2016,1,20]],"date-time":"2016-01-20T00:00:00Z","timestamp":1453248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>We reported herein the synthesis, antifungal activity, docking and in silico ADME prediction studies of four novel series of sulfones 6a\u2013f, 8a\u2013c, 10a\u2013f and 12a\u2013c. 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\u20130.81 \u00b5M) relative to fluconazole (MIC = 1.00 \u00b5M). Furthermore, 10e and 12a elicited a remarkable and selective antifungal activity against Aspergillus sp. and the dermatophytic fungi (MIC: 0.16\u20130.79 \u00b5M) relative to fluconazole (MIC: 2\u20132.6 \u00b5M). Moreover, the docking results of the sulfones 6a, 8a, 10a and 10b at the active site of CYT P450 14\u03b1-sterol demethylase showed a comparable binding interaction (interaction Energy = \u221234.87 to \u221242.43 kcal\/mol) with that of fluconazole (IE = \u221240.37 kcal\/mol).<\/jats:p>","DOI":"10.3390\/molecules21010114","type":"journal-article","created":{"date-parts":[[2016,1,20]],"date-time":"2016-01-20T11:19:41Z","timestamp":1453288781000},"page":"114","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Synthesis, Biological Evaluation and Molecular Docking of Certain Sulfones as Potential Nonazole Antifungal Agents"],"prefix":"10.3390","volume":"21","author":[{"given":"Mohamed","family":"Fares","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo 11829, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7937-0084","authenticated-orcid":false,"given":"Mohamed","family":"Said","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo 11829, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Alsherbiny","sequence":"additional","affiliation":[{"name":"Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radwa","family":"Eladwy","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo 11829, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadia","family":"Almahli","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo 11829, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa","family":"Abdel-Aziz","sequence":"additional","affiliation":[{"name":"The Regional Center for Mycology and Biotechnology, Al-Azhar University, Cairo 11759, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1011-0276","authenticated-orcid":false,"given":"Hazem","family":"Ghabbour","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P. O. Box 2457, Riyadh 11451, Saudi Arabia"},{"name":"Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6996-4017","authenticated-orcid":false,"given":"Wagdy","family":"Eldehna","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo 11829, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2606-2504","authenticated-orcid":false,"given":"Hatem","family":"Abdel-Aziz","sequence":"additional","affiliation":[{"name":"Department of Applied Organic Chemistry, National Research Center, Dokki, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2016,1,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5678","DOI":"10.1016\/j.bmc.2012.04.045","article-title":"The biology and chemistry of antifungal agents: A review","volume":"20","author":"Kathiravan","year":"2012","journal-title":"Bioorg. Med. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.1021\/bm500257s","article-title":"Materials with fungi-bioinspired surface for efficient binding and fungi-sensitive release of antifungal agents","volume":"15","author":"Segura","year":"2014","journal-title":"Biomacromolecules"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1111\/myc.12189","article-title":"Comparative study of microsporum canis isolates by DNA fingerprinting","volume":"57","author":"Shafiee","year":"2014","journal-title":"Mycoses"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1128\/CMR.00029-06","article-title":"Epidemiology of invasive candidiasis: A persistent public health problem","volume":"20","author":"Pfaller","year":"2007","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1128\/CMR.12.4.501","article-title":"Antifungal agents: Mode of action, mechanisms of resistance, and correlation of these mechanisms with bacterial resistance","volume":"12","author":"Ghannoum","year":"1999","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1016\/S1473-3099(13)70318-9","article-title":"Antibiotic resistance-the need for global solutions","volume":"13","author":"Laxminarayan","year":"2013","journal-title":"Lancet Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.ijantimicag.2007.07.019","article-title":"Recent advances and challenges in the treatment of invasive fungal infections","volume":"30","author":"Shao","year":"2007","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"117","DOI":"10.3810\/pgm.2001.01.830","article-title":"Superficial fungal infection of the skin. Where and how it appears help determine therapy","volume":"109","author":"Zuber","year":"2001","journal-title":"Postgrad. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1086\/421946","article-title":"Nosocomial bloodstream infections in us hospitals: Analysis of 24,179 cases from a prospective nationwide surveillance study","volume":"39","author":"Wisplinghoff","year":"2004","journal-title":"Clin. Infect. Dis"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/S0190-9622(96)80135-6","article-title":"Guidelines of care for superficial mycotic infections of the skin: Tinea corporis, tinea cruris, tinea faciei, tinea manuum, and tinea pedis. Guidelines\/Outcomes Committee. American academy of dermatology","volume":"34","author":"Drake","year":"1996","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_11","first-page":"40","article-title":"Mycotic infections. Effective management of conditions involving the skin, hair, and nails","volume":"55","author":"Goldstein","year":"2000","journal-title":"Geriatrics"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"805","DOI":"10.4065\/mcp.2011.0247","article-title":"Current concepts in antifungal pharmacology","volume":"86","author":"Lewis","year":"2011","journal-title":"Mayo Clin. Proc."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1021\/jm301501k","article-title":"Sulfonylureas have antifungal activity and are potent inhibitors of candida albicans acetohydroxyacid synthase","volume":"56","author":"Lee","year":"2013","journal-title":"J. Med. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1128\/AAC.46.3.922-924.2002","article-title":"Efficacy of ravuconazole in treatment of systemic murine histoplasmosis","volume":"46","author":"Clemons","year":"2002","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1128\/JCM.01901-07","article-title":"In vitro susceptibility of invasive isolates of Candida spp. To anidulafungin, caspofungin, and micafungin: Six years of global surveillance","volume":"46","author":"Pfaller","year":"2008","journal-title":"J. Clin. Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/S1054-3589(08)60129-5","article-title":"Clinical pharmacology of systemic antifungal agents: A comprehensive review of agents in clinical use, current investigational compounds, and putative targets for antifungal drug development","volume":"44","author":"Groll","year":"1998","journal-title":"Adv. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1086\/524071","article-title":"Antimicrobial resistance: Resistance to antifungal agents: Mechanisms and clinical impact","volume":"46","author":"Kanafani","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"ref_18","unstructured":"Ashley, E.S.D. (2010). Pharmacology of Azole Antifungal Agents, Informa Healthcare USA."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5293","DOI":"10.1021\/jm0701167","article-title":"Synthesis and antifungal activities of novel 2-aminotetralin derivatives","volume":"50","author":"Yao","year":"2007","journal-title":"J. Med. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1128\/CMR.12.1.40","article-title":"Current and emerging azole antifungal agents","volume":"12","author":"Sheehan","year":"1999","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1002\/j.1875-9114.1998.tb03856.x","article-title":"Food interaction and steady-state pharmacokinetics of itraconazole oral solution in healthy volunteers","volume":"18","author":"Barone","year":"1998","journal-title":"Pharmacotherapy"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1016\/j.ejmech.2006.12.015","article-title":"Rapid synthesis of sulfone derivatives as potential anti-infectious agents","volume":"42","author":"Curti","year":"2007","journal-title":"Eur. J. Med. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.ejmech.2012.09.004","article-title":"Synthesis and antibacterial and antifungal evaluation of some chalcone based sulfones and bisulfones","volume":"59","author":"Konduru","year":"2013","journal-title":"Eur. J. Med. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.ejmech.2012.06.014","article-title":"Synthesis, antimicrobial and cytotoxic activities of sulfone linked bis heterocycles","volume":"54","author":"Muralikrishna","year":"2012","journal-title":"Eur. J. Med. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1155\/2014\/154357","article-title":"Design, synthesis, and molecular docking of 1-(1-(4-chlorophenyl)-2-(phenylsulfonyl)ethylidene)-2-phenylhydrazine as potent nonazole anticandidal agent","volume":"2014","author":"Ghabbour","year":"2014","journal-title":"J. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1248\/bpb.b15-00439","article-title":"Synthesis, in vitro and in silico studies of some novel 5-nitrofuran-2-yl hydrazones as antimicrobial and antitubercular agents","volume":"38","author":"Eldehna","year":"2015","journal-title":"Biol. Pharm. Bull."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"8719","DOI":"10.3390\/ijms16048719","article-title":"Synthesis, biological evaluation and 2D-QSAR study of halophenyl bis-hydrazones as antimicrobial and antitubercular agents","volume":"16","author":"Eldehna","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4985","DOI":"10.1016\/j.ejmech.2009.09.002","article-title":"Stereoselective synthesis and antimicrobial activity of benzofuran-based (1E)-1-(piperidin-1-yl)-n 2-arylamidrazones","volume":"44","author":"Mekawey","year":"2009","journal-title":"Eur. J. Med. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2959","DOI":"10.1021\/jo01033a037","article-title":"Azohydrazone conversion. II. The coupling of diazonium ion with \u03b2-diketones","volume":"29","author":"Yao","year":"1964","journal-title":"J. Org. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1002\/jhet.69","article-title":"Dimethylformamide dimethyl acetal as a building block in heterocyclic synthesis","volume":"46","author":"Sherif","year":"2009","journal-title":"J. Heterocycl. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1021\/jm960803q","article-title":"Synthesis and biological evaluation of the 1, 5-diarylpyrazole class of cyclooxygenase-2 inhibitors: Identification of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide (SC-58635, celecoxib)","volume":"40","author":"Penning","year":"1997","journal-title":"J. Med. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1128\/AAC.45.7.1943-1946.2001","article-title":"Search for new drugs for treatment of tuberculosis","volume":"45","author":"Program","year":"2001","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3068","DOI":"10.1073\/pnas.061562898","article-title":"Crystal structure of cytochrome p450 14alpha -sterol demethylase (CYP51) from mycobacterium tuberculosis in complex with azole inhibitors","volume":"98","author":"Podust","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1093\/jnci\/82.13.1107","article-title":"New colorimetric cytotoxicity assay for anticancer-drug screening","volume":"82","author":"Skehan","year":"1990","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.ejmech.2014.06.027","article-title":"Synthesis and antitumor activity of pyrido [2,3-d]pyrimidine and pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidine derivatives that induce apoptosis through g1 cell-cycle arrest","volume":"83","author":"Fares","year":"2014","journal-title":"Eur. J. Med. Chem."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/21\/1\/114\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:17:59Z","timestamp":1760210279000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/21\/1\/114"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,1,20]]},"references-count":35,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,1]]}},"alternative-id":["molecules21010114"],"URL":"https:\/\/doi.org\/10.3390\/molecules21010114","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,1,20]]}}}