TY - JOUR
T1 - Synthesis and biological evaluation of new bisindole-imidazopyridine hybrids as apoptosis inducers
AU - Sunkari, Satish
AU - Bonam, Srinivasa Reddy
AU - Rao, A. V.Subba
AU - Riyaz, Sd
AU - Lakshma Nayak, V.
AU - Kumar, Halmuthur Mahabalarao Sampath
AU - Kamal, Ahmed
AU - Nagendra Babu, Bathini
N1 - Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/6
Y1 - 2019/6
N2 - A series of diindolylmethanes (5a-t) were designed, synthesized, and examined for their cytotoxicity against four human cancer cell lines like prostate (DU-145), lung (A549), breast (MCF-7) and cervical cancer (HeLa). These results revealed that among all the hybrids, two (5k and 5r) were identified and exhibited significant cytotoxic effect against A549 cancer cells with IC 50 values of 1.65 ± 0.3 and 1.80 ± 0.8 µM respectively. To investigate the reasons for the cytotoxic activity, the conventional biological assays were carried out with 5k and 5r on the A549 cancer cells. Both hybrids led to the arrest of A549 cell lines at the G2/M phase of the cell cycle and strongly induced apoptosis. Further the apoptotic effects of 5k and 5r were confirmed by ROS, annexin-V FITC, and mitochondrial membrane potential. Moreover, structure–activity relationships were elucidated with various substitutions on these hybrids.
AB - A series of diindolylmethanes (5a-t) were designed, synthesized, and examined for their cytotoxicity against four human cancer cell lines like prostate (DU-145), lung (A549), breast (MCF-7) and cervical cancer (HeLa). These results revealed that among all the hybrids, two (5k and 5r) were identified and exhibited significant cytotoxic effect against A549 cancer cells with IC 50 values of 1.65 ± 0.3 and 1.80 ± 0.8 µM respectively. To investigate the reasons for the cytotoxic activity, the conventional biological assays were carried out with 5k and 5r on the A549 cancer cells. Both hybrids led to the arrest of A549 cell lines at the G2/M phase of the cell cycle and strongly induced apoptosis. Further the apoptotic effects of 5k and 5r were confirmed by ROS, annexin-V FITC, and mitochondrial membrane potential. Moreover, structure–activity relationships were elucidated with various substitutions on these hybrids.
KW - Apoptosis
KW - Bisindole-imidazopyridine
KW - Cytotoxicity
KW - Heterocyclic
KW - ROS
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U2 - 10.1016/j.bioorg.2019.03.061
DO - 10.1016/j.bioorg.2019.03.061
M3 - Article
C2 - 30927589
AN - SCOPUS:85063413293
SN - 0045-2068
VL - 87
SP - 484
EP - 494
JO - Bioorganic Chemistry
JF - Bioorganic Chemistry
ER -