Synthesis and Biological evaluation of novel 4β-[(5-substituted)-1,2,3,4-tetrazolyl] podophyllotoxins as anticancer compounds

• Published in: Bioorganic & medicinal chemistry letters 2015-07, Vol.25 (14), p.2860-2863
• Main Authors: Hyder, Irfan, Yedlapudi, Deepthi, Kalivendi, Shasi V., Khazir, Jabeena, Ismail, Tabasum, Nalla, Naresh, Miryala, Sreekanth, Sampath Kumar, Halmuthur M.
• Format: Article
• Language: English
• Subjects: Anticancer activity; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Cell Cycle Checkpoints - drug effects; Cell Line, Tumor; Cell Survival - drug effects; HeLa Cells; Humans; Podophyllotoxin - chemistry; Podophyllotoxin - pharmacology; Structure-Activity Relationship; Tetrazolyl podophyllotoxin; Tubulin - chemistry; Tubulin - metabolism; Tubulin Modulators - chemical synthesis; Tubulin Modulators - pharmacology; Tubulin polymerization
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2015.04.053

[Display omitted] A series of novel 4β-[(5-substituted)-1,2,3,4-tetrazolyl] podophyllotoxin derivatives were synthesized by employing azide-nitrile click chemistry approach. All the derivatives were evaluated for their cytotoxicity against a panel of four human cancer cell lines and their IC50 values were found to be in the range of 2.4–29.06μM. The cytotoxicity exhibited by the majority of test compounds were found to comparable and often more effective than doxorubicin and all compounds exhibited higher cytotoxicity on A-549 cell lines. Cell cycle analysis showed that the novel 4β-[(5-substituted)-1,2,3,4-tetrazolyl] podophyllotoxins resulted in cell cycle arrest at G2/M phase and were also found to be the potent inhibitors of tubulin polymerization in vitro.