title: Synthesis and biological evaluation of novel isoxazoles and triazoles linked 6-hydroxycoumarin as potent cytotoxic agents.
abstract: A new series of diverse isoxazoles and triazoles linked 6-hydroxycoumarin (1) were synthesized using click chemistry approach. All the derivatives were subjected to 3-(4,5-dimethylthiazol-yl)-diphenyl tetrazoliumbromide (MTT) cytotoxicity screening against a panel of five different human cancer cell lines viz. prostate (PC-3), colon (HCT-116 and Colo-205), leukemia (HL-60) and lung (A-549) to check their cytotoxic potential. Interestingly, among the tested molecules, some of the analogs displayed better cytotoxic activity than the parent 6-hydroxycoumarin (1). Of the synthesized isoxazoles, compounds 10 and 13 showed the best activity with IC50 of 8.2 and 13.6 μM against PC-3 cancer cell line, while as, among the triazoles, compounds 23 and 25 were the most active with the IC50 of 10.2 and 12.6 μM against A-549 cancer cell line. The other derivatives showed almost comparable activity with that of the parent molecule. The present study resulted in identification of ortho substituted isoxazole and triazole derivatives of 6-hydroxycoumarin as effective cytotoxic agents against prostate (PC-3) and lung (A-549) cancer cell lines, respectively.
authors.affiliation: Bioorganic Chemistry Division, Indian Institute of Integrative Medicine (CSIR), Srinagar 190005, India.
authors.lastname: Shakeel-u-Rehman
authors.affiliation: Department of Chemistry, National Institute of Technology, Srinagar 190006, India.
authors.lastname: Masood-ur-Rahman
authors.affiliation: Bioorganic Chemistry Division, Indian Institute of Integrative Medicine (CSIR), Jammu 180001, India.
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Tripathi
authors.affiliation: Cancer Pharmacology Division, Indian Institute of Integrative Medicine (CSIR), Jammu 180001, India.
authors.forename: Jasvinder
authors.initials: J
authors.lastname: Singh
authors.affiliation: Department of Chemistry, National Institute of Technology, Srinagar 190006, India.
authors.forename: Tabassum
authors.initials: T
authors.lastname: Ara
authors.affiliation: Bioorganic Chemistry Division, Indian Institute of Integrative Medicine (CSIR), Jammu 180001, India. Electronic address: skoul@iiim.ac.in.
authors.forename: Surrinder
authors.initials: S
authors.lastname: Koul
authors.affiliation: Bioorganic Chemistry Division, Indian Institute of Integrative Medicine (CSIR), Jammu 180001, India. Electronic address: farooqprince100@yahoo.in.
authors.forename: Saleem
authors.initials: S
authors.lastname: Farooq
authors.affiliation: Cancer Pharmacology Division, Indian Institute of Integrative Medicine (CSIR), Jammu 180001, India.
authors.forename: Anupurna
authors.initials: A
authors.lastname: Kaul
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D018922:HL-60 Cells; D006801:Humans; D007555:Isoxazoles / Q000737:chemistry / Q000633:toxicity*; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry / Q000633:toxicity*
chemical_list: D000970:Antineoplastic Agents; D003374:Coumarins; D007555:Isoxazoles; D014230:Triazoles
keywords: 6-Hydroxycoumarin; Cytotoxic; Isoxazoles; MTT assay; Triazoles