title: Designing and synthesis of novel antimicrobial heterocyclic analogs of fatty acids.
abstract: Novel series of long chain isoxazole derivatives were designed as inhibitors of Cytochrome P450-14DM14a-demethylase from Candida albicans and ribosomal subunit of S12 protein from Escherichia coli. The novel compounds (6-10) were synthesized through 1,3-dipolar cycloaddition of nitrile oxide to long chain alkynoic acid and alkenyl/hydroxyalkenyl esters and tested for their antimicrobial activity by disk diffusion assay and MIC by broth micro dilution method. After predicting the hidden potential and drug-likeness of compounds, ADMET-related descriptors were also calculated to predict pharmacokinetic properties. Molecular docking studies have been performed to evaluate possible mode of action of molecules in active site of receptor. Compounds (9 and 10) showed excellent antimicrobial activity nearly equivalent to the control compounds.
authors.affiliation: Department of Chemistry, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Aiman
authors.initials: A
authors.lastname: Ahmad
authors.forename: Anis
authors.initials: A
authors.lastname: Ahmad
authors.forename: Himani
authors.initials: H
authors.lastname: Varshney
authors.forename: Abdul
authors.initials: A
authors.lastname: Rauf
authors.forename: Mohd
authors.initials: M
authors.lastname: Rehan
authors.forename: Naidu
authors.initials: N
authors.lastname: Subbarao
authors.forename: Asad U
authors.initials: AU
authors.lastname: Khan
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D002175:Candida / Q000187:drug effects*; D003500:Cyclization; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D005227:Fatty Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D012984:Software; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D005227:Fatty Acids; D006571:Heterocyclic Compounds
keywords: 1,3-Dipolar-cycloaddition; Fatty acid; MIC; MR; MRSA; MV; MW; Mode of action; PASS; PSA; SAR; Sa; Staphylococcus aureus; methicillin resistant Staphylococcus aureus; minimal inhibitory concentration; molar refractivity; molecular volume; molecular weight; polar surface area; predicted activity spectrum of substances; structure–activity relationship