TY - JOUR
T1 - Pyrazole-oxadiazole conjugates
T2 - Synthesis, antiproliferative activity and inhibition of tubulin polymerization
AU - Kamal, Ahmed
AU - Shaik, Anver Basha
AU - Polepalli, Sowjanya
AU - Santosh Reddy, Vangala
AU - Bharath Kumar, G.
AU - Gupta, Soma
AU - Rama Krishna, K. V.S.
AU - Nagabhushana, Ananthamurthy
AU - Mishra, Rakesh K.
AU - Jain, Nishant
N1 - Publisher Copyright:
© the Partner Organisations 2014.
PY - 2014/10/28
Y1 - 2014/10/28
N2 - A number of pyrazole-oxadiazole conjugates were synthesized and evaluated for their ability to function as antiproliferative agents on various human cancer cell lines. These conjugates are comprised of pyrazole and oxadiazole scaffolds closely attached to each other without any spacer as two structural classes. The Type I class has a trimethoxy substituent and the type II class has a 3,4-(methylenedioxy) substituent on their A rings. Among these conjugates, 11a, 11d and 11f manifest potent cytotoxicity with IC50values ranging from 1.5 μM to 11.2 μM and inhibit tubulin polymerization with IC50values of 1.3 μM, 3.9 μM and 2.4 μM respectively. The cell cycle assay showed that treatment with these conjugates results in accumulation of cells in the G2/M phase and disrupts the microtubule network. Elucidation of zebrafish embryos revealed that the conjugates cause developmental defects. Molecular docking simulations determined the binding modes of these potent conjugates at the colchicine site of tubulin.
AB - A number of pyrazole-oxadiazole conjugates were synthesized and evaluated for their ability to function as antiproliferative agents on various human cancer cell lines. These conjugates are comprised of pyrazole and oxadiazole scaffolds closely attached to each other without any spacer as two structural classes. The Type I class has a trimethoxy substituent and the type II class has a 3,4-(methylenedioxy) substituent on their A rings. Among these conjugates, 11a, 11d and 11f manifest potent cytotoxicity with IC50values ranging from 1.5 μM to 11.2 μM and inhibit tubulin polymerization with IC50values of 1.3 μM, 3.9 μM and 2.4 μM respectively. The cell cycle assay showed that treatment with these conjugates results in accumulation of cells in the G2/M phase and disrupts the microtubule network. Elucidation of zebrafish embryos revealed that the conjugates cause developmental defects. Molecular docking simulations determined the binding modes of these potent conjugates at the colchicine site of tubulin.
UR - http://www.scopus.com/inward/record.url?scp=84907482364&partnerID=8YFLogxK
U2 - 10.1039/c4ob01152j
DO - 10.1039/c4ob01152j
M3 - Article
C2 - 25181296
AN - SCOPUS:84907482364
SN - 1477-0520
VL - 12
SP - 7993
EP - 8007
JO - Organic and Biomolecular Chemistry
JF - Organic and Biomolecular Chemistry
IS - 40
ER -