title: Ultrasound- and Molecular Sieves-Assisted Synthesis, Molecular Docking and Antifungal Evaluation of 5-(4-(Benzyloxy)-substituted phenyl)-3-((phenylamino)methyl)-1,3,4-oxadiazole-2(3H)-thiones.
abstract: A novel series of 5-(4-(benzyloxy)substituted phenyl)-3-((phenyl amino)methyl)-1,3,4-oxadiazole-2(3H)-thione Mannich bases 6a-o were synthesized in good yield from the key compound 5-(4-(benzyloxy)phenyl)-1,3,4-oxadiazole-2(3H)-thione by aminomethylation with paraformaldehyde and substituted amines using molecular sieves and sonication as green chemistry tools. The antifungal activity of the new products was evaluated against seven human pathogenic fungal strains, namely, Candida albicans ATCC 24433, Candida albicans ATCC 10231, Candida glabrata NCYC 388, Cryptococcus neoformans ATCC 34664, Cryptococcus neoformans PRL 518, Aspergillus fumigatus NCIM 902 and Aspergillus niger ATCC 10578. The synthesized compounds 6d, 6f, 6g, 6h and 6j exhibited promising antifungal activity against the tested fungal pathogens. In molecular docking studies, derivatives 6c, 6f and 6i showed good binding at the active site of C. albicans cytochrome P450 enzyme lanosterol 14 α-demethylase. The in vitro antifungal activity results and docking studies indicated that the synthesized compounds have potential antifungal activity and can be further optimized as privileged scaffolds to design and develop potent antifungal drugs.
authors.affiliation: Maulana Azad P. G. and Research Centre, Dr. Rafiq Zakaria Campus, Rauza Baug, Aurangabad 431001, India. urjasatish@gmail.com.
authors.forename: Urja D
authors.initials: UD
authors.lastname: Nimbalkar
authors.affiliation: Biochemical Sciences Division, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pashan, Pune 411008, India. sg.tupe@ncl.res.in.
authors.forename: Santosh G
authors.initials: SG
authors.lastname: Tupe
authors.affiliation: Departamento de Química Orgánica, Facultad de Ciencias, Universidad of Santiago De Compostela, Alfonso X el Sabio, Lugo 27002, Spain. julioa.seijas@usc.es.
authors.forename: Julio A
authors.initials: JA
authors.lastname: Seijas Vazquez
authors.affiliation: Y. B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Campus, Rauza Baug, Aurangabad 431001, India. firozakhan05@gmail.com.
authors.forename: Firoz A Kalam
authors.initials: FA
authors.lastname: Khan
authors.affiliation: Y. B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Campus, Rauza Baug, Aurangabad 431001, India. jnsangshetti@rediffmail.com.
authors.forename: Jaiprakash N
authors.initials: JN
authors.lastname: Sangshetti
authors.affiliation: Y. B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Campus, Rauza Baug, Aurangabad 431001, India. annapratimanikalje@gmail.com.
authors.forename: Anna Pratima G
authors.initials: AP
authors.lastname: Nikalje
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001232:Aspergillus fumigatus / Q000187:drug effects; D001234:Aspergillus niger / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects; D041221:Candida glabrata / Q000187:drug effects; D020134:Catalytic Domain / Q000187:drug effects; D003455:Cryptococcus neoformans / Q000187:drug effects; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D058886:Sterol 14-Demethylase / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D014465:Ultrasonics
chemical_list: D000935:Antifungal Agents; D010069:Oxadiazoles; D058886:Sterol 14-Demethylase
keywords: 1,3,4-oxadiazoles; Mannich reaction; antifungal activity; molecular docking; molecular sieves; ultrasound