TY - JOUR
T1 - Design, synthesis of phenstatin/isocombretastatin-oxindole conjugates as antimitotic agents
AU - Kumar, G. Bharath
AU - Nayak, V. Lakshma
AU - Sayeed, Ibrahim Bin
AU - Reddy, Vangala Santhosh
AU - Shaik, Anver Basha
AU - Mahesh, Rasala
AU - Baig, Mirza Feroz
AU - Shareef, Mohd Adil
AU - Ravikumar, A.
AU - Kamal, Ahmed
N1 - Publisher Copyright:
© 2016 Published by Elsevier Ltd.
PY - 2016/4/15
Y1 - 2016/4/15
N2 - A series of phenstatin/isocombretastatin-oxindole conjugates was synthesized and tested for their cytotoxic activity against five human cancer cells such as prostate (DU-145), lung (A549), colon (HT-29), breast (MCF-7), liver (HepG2) cancer cells with IC50 values ranging from 0.049 to 38.90 μM. Amongst them, two conjugates (5c and 5d) showed broad spectrum of antiproliferative efficacy on lung cancer cells with an IC50 value of 79 nM and 93 nM, respectively, whereas on colon cancer cells with an IC50 values 45 nM and 49 nM, respectively. In addition, cell cycle assay revealed that these conjugates (5c and 5d) arrest at the G2/M phase and leads to apoptotic cell death which was confirmed by Annexin V-FITC and mitochondrial membrane depolarization. Further, the tubulin polymerization assay analysis results suggest that these conjugates particularly 5c and 5d exhibit significant inhibitory effect on the tubulin assembly with an IC50 value of 1.23 μM and 1.01 μM, respectively. Molecular docking studies indicated that these compounds (5c and 5d) occupy the colchicine binding site of the tubulin.
AB - A series of phenstatin/isocombretastatin-oxindole conjugates was synthesized and tested for their cytotoxic activity against five human cancer cells such as prostate (DU-145), lung (A549), colon (HT-29), breast (MCF-7), liver (HepG2) cancer cells with IC50 values ranging from 0.049 to 38.90 μM. Amongst them, two conjugates (5c and 5d) showed broad spectrum of antiproliferative efficacy on lung cancer cells with an IC50 value of 79 nM and 93 nM, respectively, whereas on colon cancer cells with an IC50 values 45 nM and 49 nM, respectively. In addition, cell cycle assay revealed that these conjugates (5c and 5d) arrest at the G2/M phase and leads to apoptotic cell death which was confirmed by Annexin V-FITC and mitochondrial membrane depolarization. Further, the tubulin polymerization assay analysis results suggest that these conjugates particularly 5c and 5d exhibit significant inhibitory effect on the tubulin assembly with an IC50 value of 1.23 μM and 1.01 μM, respectively. Molecular docking studies indicated that these compounds (5c and 5d) occupy the colchicine binding site of the tubulin.
KW - Annexin V-FITC and mitochondrial membrane depolarization
KW - Phenstatin/isocombretastatin-oxindole
KW - Tubulin depolymerization
UR - https://www.scopus.com/pages/publications/84960145585
U2 - 10.1016/j.bmc.2016.02.047
DO - 10.1016/j.bmc.2016.02.047
M3 - Article
C2 - 26970659
AN - SCOPUS:84960145585
SN - 0968-0896
VL - 24
SP - 1729
EP - 1740
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 8
ER -