title: Synthesis and Biological evaluation of novel 4β-[(5-substituted)-1,2,3,4-tetrazolyl] podophyllotoxins as anticancer compounds.
abstract: 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.
authors.affiliation: 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.
authors.forename: Irfan
authors.initials: I
authors.lastname: Hyder
authors.affiliation: Centre for Chemical Biology Division, CSIR - Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors.forename: Deepthi
authors.initials: D
authors.lastname: Yedlapudi
authors.affiliation: Centre for Chemical Biology Division, CSIR - Indian Institute of Chemical Technology, Hyderabad 500007, India. Electronic address: kalivendi@iict.res.in.
authors.forename: Shasi V
authors.initials: SV
authors.lastname: Kalivendi
authors.affiliation: Medicinal Chemistry Division, Indian Institute of Integrative Medicine, Jammu 180001, India.
authors.forename: Jabeena
authors.initials: J
authors.lastname: Khazir
authors.affiliation: Medicinal Chemistry Division, Indian Institute of Integrative Medicine, Jammu 180001, India.
authors.forename: Tabasum
authors.initials: T
authors.lastname: Ismail
authors.affiliation: NPC Division, CSIR - Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors.forename: Naresh
authors.initials: N
authors.lastname: Nalla
authors.affiliation: 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.
authors.forename: Sreekanth
authors.initials: S
authors.lastname: Miryala
authors.affiliation: 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: sampath@iict.res.in.
authors.forename: Halmuthur M
authors.initials: HM
authors.lastname: Sampath Kumar
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D011034:Podophyllotoxin / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D014404:Tubulin; D050257:Tubulin Modulators; D011034:Podophyllotoxin
keywords: Anticancer activity; Tetrazolyl podophyllotoxin; Tubulin polymerization