Synthesis and Biological evaluation of novel 4β-[(5-substituted)-1,2,3,4-tetrazolyl] podophyllotoxins as anticancer compounds
- Bioorg Med Chem Lett. 2015 Jul 15;25(14):2860-3. doi: 10.1016/j.bmcl.2015.04.053.
- 1. NPC Division, CSIR - Indian Institute of Chemical Technology, Hyderabad 500007, India; Academy of Scientific and Innovative Research, CSIR - Indian Institute of Chemical Technology, Hyderabad 500007, India.
- 2. Centre for Chemical Biology Division, CSIR - Indian Institute of Chemical Technology, Hyderabad 500007, India.
- 3. Centre for Chemical Biology Division, CSIR - Indian Institute of Chemical Technology, Hyderabad 500007, India. Electronic address: [email protected].
- 4. Medicinal Chemistry Division, Indian Institute of Integrative Medicine, Jammu 180001, India.
- 5. NPC Division, CSIR - Indian Institute of Chemical Technology, Hyderabad 500007, India.
- 6. NPC Division, CSIR - Indian Institute of Chemical Technology, Hyderabad 500007, India; Academy of Scientific and Innovative Research, CSIR - Indian Institute of Chemical Technology, Hyderabad 500007, India. Electronic address: [email protected].
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 2.4-29.06 μM. 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.