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Synthesis and Biological Evaluation of Imidazopyridine–Oxindole Conjugates as Microtubule‐Targeting Agents
Author(s) -
Kamal Ahmed,
Reddy Vangala Santhosh,
Karnewar Santosh,
Chourasiya Sumit S.,
Shaik Anver Basha,
Kumar G. Bharath,
Kishor Chandan,
Reddy M. Kashi,
Narasimha Rao M. P.,
Nagabhushana Ananthamurthy,
Ramakrishna Kallaganti V. S.,
Addlagatta Anthony,
Kotamraju Srigiridhar
Publication year - 2013
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201300308
Subject(s) - imidazopyridine , tubulin , chemistry , microtubule , conjugate , apoptosis , stereochemistry , biochemistry , biology , microbiology and biotechnology , mathematical analysis , mathematics
A library of imidazopyridine–oxindole conjugates was synthesised and investigated for anticancer activity against various human cancer cell lines. Some of the tested compounds, such as 10 a , 10 e , 10 f , and 10 k , exhibited promising antiproliferative activity with GI 50 values ranging from 0.17 to 9.31 μ M . Flow cytometric analysis showed that MCF‐7 cells treated by these compounds arrested in the G 2 /M phase of the cell cycle in a concentration‐dependent manner. More particularly, compound 10 f displayed a remarkable inhibitory effect on tubulin polymerisation. All the compounds depolarised mitochondrial membrane potential and caused apoptosis. These results are further supported by the decreased phosphorylation of Akt at Ser473. Studies on embryonic development revealed that the lead compounds 10 f and 10 k caused delay in the development of zebra fish embryos. Docking of compound 10 f with tubulin protein suggested that the imidazo[1,2‐ a ]pyridine moiety occupies the colchicine binding site of tubulin.