title: 4β-[(4-Alkyl)-1,2,3-triazol-1-yl] podophyllotoxins as anticancer compounds: design, synthesis and biological evaluation.
abstract: A series of 4β-[(4-alkyl)-1,2,3-triazol-1-yl] podophyllotoxin derivatives were designed in silico, synthesised by employing click chemistry approach, and evaluated for cytotoxicity against a panel of human cancer cell lines (SF-295, A-549, PC-3, Hep-2, HCT-15 and MCF-7). Majority of the compounds proved to be more potent than etoposide and select compounds exhibited significant anticancer activity with IC50 values in the range of 0.001-1 μM. DNA fragmentation and flow-cytometric results reveals that 4β-[(4-alkyl)-1,2,3-triazol-1-yl] podophyllotoxin derivatives induce dose dependent apoptosis. Docking experiments showed a good correlation between their calculated interaction energies with the topoisomerase-II and the observed IC50 values of all these compounds.
authors.affiliation: Synthetic and Biological Chemistry Division, Indian Institute of Integrative Medicine, Canal road, Jammu 180001, India.
authors.forename: Doma Mahendhar
authors.initials: DM
authors.lastname: Reddy
authors.forename: Jada
authors.initials: J
authors.lastname: Srinivas
authors.forename: Gousia
authors.initials: G
authors.lastname: Chashoo
authors.forename: Ajit K
authors.initials: AK
authors.lastname: Saxena
authors.forename: H M
authors.initials: HM
authors.lastname: Sampath Kumar
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D011034:Podophyllotoxin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D011034:Podophyllotoxin