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  • Title: 4β-[(4-Alkyl)-1,2,3-triazol-1-yl] podophyllotoxins as anticancer compounds: design, synthesis and biological evaluation.
    Author: Reddy DM, Srinivas J, Chashoo G, Saxena AK, Sampath Kumar HM.
    Journal: Eur J Med Chem; 2011 Jun; 46(6):1983-91. PubMed ID: 21477899.
    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.
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