TY - JOUR
T1 - Combretastatin linked 1,3,4-oxadiazole conjugates as a Potent Tubulin Polymerization inhibitors
AU - Kamal, Ahmed
AU - Srikanth, P. S.
AU - Vishnuvardhan, M. V.P.S.
AU - Kumar, G. Bharath
AU - Suresh Babu, Korrapati
AU - Hussaini, S. M.Ali
AU - Kapure, Jeevak Sopanrao
AU - Alarifi, Abdullah
N1 - Publisher Copyright:
© 2016 Published by Elsevier Inc.
PY - 2016/4/1
Y1 - 2016/4/1
N2 - A new class of combretastatin linked 1,3,4-oxadiazoles were designed, synthesized and screened for their cytotoxic activity against five human cancer cell lines such as HeLa, DU-145, A549, MDA-MB-231 and B16. These compounds showed significant cytotoxicity with IC50 values in the range 0.118-54.32 μM. Conjugate 5m displayed potent antiproliferative activity against DU-145 cell line. Flow cytometric analysis revealed that these compounds arrested the cell cycle in G2/M phase. Moreover, the tubulin polymerization assay and immunofluorescence analysis indicate that 5m exhibits potent inhibitory effect on the tubulin assembly. Further, DNA fragmentation and Hoecst staining assays confirm that 5m induces apoptosis. Molecular docking studies and competitive binding assay indicated that 5m effectively bind at the colchicine binding site of the tubulin.
AB - A new class of combretastatin linked 1,3,4-oxadiazoles were designed, synthesized and screened for their cytotoxic activity against five human cancer cell lines such as HeLa, DU-145, A549, MDA-MB-231 and B16. These compounds showed significant cytotoxicity with IC50 values in the range 0.118-54.32 μM. Conjugate 5m displayed potent antiproliferative activity against DU-145 cell line. Flow cytometric analysis revealed that these compounds arrested the cell cycle in G2/M phase. Moreover, the tubulin polymerization assay and immunofluorescence analysis indicate that 5m exhibits potent inhibitory effect on the tubulin assembly. Further, DNA fragmentation and Hoecst staining assays confirm that 5m induces apoptosis. Molecular docking studies and competitive binding assay indicated that 5m effectively bind at the colchicine binding site of the tubulin.
KW - 1,3,4-Oxadiazole
KW - Apoptotic cell death
KW - Colchicine binding
KW - Molecular modeling
KW - Tubulin polymerization
UR - http://www.scopus.com/inward/record.url?scp=84959283930&partnerID=8YFLogxK
U2 - 10.1016/j.bioorg.2016.02.007
DO - 10.1016/j.bioorg.2016.02.007
M3 - Article
C2 - 26943479
AN - SCOPUS:84959283930
SN - 0045-2068
VL - 65
SP - 126
EP - 136
JO - Bioorganic Chemistry
JF - Bioorganic Chemistry
ER -