title: Design, synthesis and biological evaluation of diaziridinyl quinone isoxazole hybrids.
abstract: A series of novel diaziridinyl quinone isoxazole hybrids (9a-9j) were synthesized starting from 2, 5-dimethoxy acetophenone 1 via Claisen reaction, cyclisation, alkoxy carbonylation, hydrolysis, oxidation and aziridine insertion. All the compounds were screened for antimicrobial, anti-biofilm and cytotoxic activities. Among the screened compounds, the compound 9h showed good antibacterial and anti-biofilm activities with MIC value of 3.9, 3.9, 3.9 and 7.8 μg/mL, respectively, and IC50 values of 1.9, 2.5, 2.8 and 5.1 μM, respectively, against Staphylococcus aureus MTCC 96, S. aureus MLS-16 MTCC 2940, Bacillus subtilis MTCC 121 and Klebsiella planticola MTCC 530, and also exhibited potent antifungal activity against Candida albicans MTCC 227, C. albicans MTCC 854 and Candida krusei MTCC 3020 equipotent to standard miconazole (MIC value 7.8 μg/mL). All the synthesized compounds exhibited promising cytotoxicity against A549 and PC3 cell lines (IC50 values between 1 and 4 μM). Compounds 9b and 9j exhibited IC50 value of 0.5 μM which was similar to that of Mitomycin C against PC3 cell line.
authors.affiliation: Department of Medicinal Chemistry, GVK Biosciences Pvt. Ltd., Survey Nos: 125(part) & 126, IDA Mallapur, Hyderabad 500076, India; COEAMMPC & Division of Chemistry, Department of Sciences and Humanities, Vignan's Foundation for Science, Technology and Research University (VFSTRU; Vignan University), Vadlamudi, Guntur 522 213, India.
authors.forename: K Jones M
authors.initials: KJ
authors.lastname: Swapnaja
authors.affiliation: Department of Medicinal Chemistry, GVK Biosciences Pvt. Ltd., Survey Nos: 125(part) & 126, IDA Mallapur, Hyderabad 500076, India. Electronic address: satya@gvkbio.com.
authors.forename: Satyanarayana
authors.initials: S
authors.lastname: Yennam
authors.affiliation: COEAMMPC & Division of Chemistry, Department of Sciences and Humanities, Vignan's Foundation for Science, Technology and Research University (VFSTRU; Vignan University), Vadlamudi, Guntur 522 213, India.
authors.forename: Murthy
authors.initials: M
authors.lastname: Chavali
authors.affiliation: Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500007, India.
authors.forename: Y
authors.initials: Y
authors.lastname: Poornachandra
authors.affiliation: Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500007, India.
authors.forename: C Ganesh
authors.initials: CG
authors.lastname: Kumar
authors.affiliation: Department of Biology, GVK Biosciences Pvt. Ltd., Survey Nos: 125(part) & 126, IDA Mallapur, Hyderabad 500076, India.
authors.forename: Krubakaran
authors.initials: K
authors.lastname: Muthusamy
authors.affiliation: Department of Biology, GVK Biosciences Pvt. Ltd., Survey Nos: 125(part) & 126, IDA Mallapur, Hyderabad 500076, India.
authors.forename: Venkatesh Babu
authors.initials: VB
authors.lastname: Jayaraman
authors.affiliation: Department of Biology, GVK Biosciences Pvt. Ltd., Survey Nos: 125(part) & 126, IDA Mallapur, Hyderabad 500076, India.
authors.forename: Premkumar
authors.initials: P
authors.lastname: Arumugam
authors.affiliation: Laboratory of X-ray Crystallography, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500007, India.
authors.forename: Sridhar
authors.initials: S
authors.lastname: Balasubramanian
authors.affiliation: Department of Medicinal Chemistry, GVK Biosciences Pvt. Ltd., Survey Nos: 125(part) & 126, IDA Mallapur, Hyderabad 500076, India.
authors.forename: Kiran Kumar
authors.initials: KK
authors.lastname: Sriram
mesh_terms: D000072283:A549 Cells; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000935:Antifungal Agents; D018441:Biofilms / Q000187:drug effects; D045744:Cell Line, Tumor; D003603:Cytotoxins / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D011809:Quinones / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D000935:Antifungal Agents; D003603:Cytotoxins; D007555:Isoxazoles; D011809:Quinones
keywords: Anti-biofilm; Antibacterial activity; Antifungal; Cytotoxicity; Quinone diaziridinyl hybrids