title: Click chemistry inspired synthesis and bioevaluation of novel triazolyl derivatives of osthol as potent cytotoxic agents.
abstract: A new series of diverse triazoles linked through the hydroxyl group of lactone ring opened osthol (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 seven different human cancer cell lines viz. colon (colo-205), colon (HCT-116), breast (T47D), lung (NCI-H322), lung (A549), prostate (PC-3) and Skin (A-431) to check their cytotoxic potential. Interestingly, among the tested molecules, most of the analogs displayed better cytotoxic activity than the parent osthol (1). Of the synthesized triazoles, compounds 8 showed the best activity with IC50 of 1.3, 4.9, 3.6, 41.0, 35.2, 26.4 and 7.2 μM against colon (Colo-205 and HCT-116), breast (T47D), lung (NCI-H322 and A549), prostate (PC-3) and Skin (A-431) cancer lines respectively. Compound 8 induced potent apoptotic effects in Colo-205 cells. The population of apoptotic cells increased from 11.4% in case of negative control to 24.1% at 25 μM of 8. Compound 8 also induced a remarkable decrease in mitochondrial membrane potential (ΛΨm) leading to apoptosis of cancer cells used. The present study resulted in identification of broad spectrum cytotoxic activity of analogs bearing electron withdrawing substituents, besides the enhanced selective activity of analogs with electron donating moieties.
authors: Bioorganic Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India. Electronic address: farooqprince100@yahoo.in.
authors: Saleem
authors: S
authors: Farooq
authors: Bioorganic Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Sanatnagar, Srinagar 190005, India.
authors: Shakeel-u-Rehman
authors: Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
authors: Aashiq
authors: A
authors: Hussain
authors: Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
authors: Abid
authors: A
authors: Hamid
authors: Department of Chemistry, University of Kashmir, Srinagar 190006, India.
authors: Mushtaq A
authors: MA
authors: Qurishi
authors: Bioorganic Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India. Electronic address: skoul@iiim.ac.in.
authors: Surrinder
authors: S
authors: Koul
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D057930:Click Chemistry; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D003603:Cytotoxins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D003374:Coumarins; D003603:Cytotoxins; C046627:osthol
keywords: Cell cycle analysis; Click chemistry; Cytotoxic; Mitochondrial membrane potential loss; Osthol; Triazole