title: Design and synthesis of novel 2H-chromen-2-one derivatives bearing 1,2,3-triazole moiety as lead antimicrobials.
abstract: A series of novel 2H-chromen-2-one derivatives decorated with 1,2,3-triazole moiety were designed and synthesized using the click reaction of azidoalkyloxy-2H-chromen-2-ones with different propargylamines. Propargylamines were obtained by alkylation of various heterocyclic amines with propargyl bromide. Newly synthesized compounds and intermediates were evaluated for their antifungal activity against four fungi (Aspergillus niger, Aspergillus fumigatus, Aspergillus flavus and Candida albicans). Antibacterial studies were also carried out against three Gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis and Staphylococcus epidermis) and four Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi and Klebsiella pneumoniae). In vitro, bioassay results showed that all the synthesized compounds exhibited excellent activity against fungal strains Aspergillus fumigatus, Aspergillus flavus and Candida albicans. Interestingly, all the compounds have shown even superior activity than the reference drug miconazole against Aspergillus fumigatus. Morpholine and N-acetyl piperazine containing compounds 10c and 10e have shown promising activity against various bacterial strains. Compound 10e was found to be most active against Pseudomonas aeruginosa. Based on, in silico pharmacokinetic studies, compounds 10a-e were identified as lead compounds for future investigation due to their lower toxicity, high drug score values and good oral bioavailability as per OECD guidelines.
authors.affiliation: Department of Chemistry, University of Delhi, Delhi 110 007, India.
authors.forename: Khushbu
authors.initials: K
authors.lastname: Kushwaha
authors.affiliation: Plasma Bioscience Research Center, Kwangwoon University, Seoul 139701, Republic of Korea.
authors.forename: Nagendra
authors.initials: N
authors.lastname: Kaushik
authors.affiliation: Department of Chemistry, University of Delhi, Delhi 110 007, India.
authors.lastname: Lata
authors.affiliation: Department of Chemistry, University of Delhi, Delhi 110 007, India. Electronic address: jainsc48@hotmail.com.
authors.forename: Subhash C
authors.initials: SC
authors.lastname: Jain
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D003374:Coumarins / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D003621:Daphnia; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D005658:Fungi / Q000187:drug effects*; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D051381:Rats; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology
chemical_list: C000596314:7-(6-(4-(4-acetylpiperazin-1-ylmethyl)-1H-1,2,3-triazol-1-yl)hexyloxy)-4-methyl-2H-chromen-2-one; D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D003374:Coumarins; D014230:Triazoles
keywords: 1,2,3-Triazole; 2H-Chromen-2-one; Antibacterial activity; Antifungal activity; Click reaction; Cup-plate method; Propargyl amines