Abstract
Cancer is one of the most dreaded human diseases, that has become an ever-increasing health problem and is a prime cause of death globally. The potential antiproliferative activity of certain indole-isatin molecular hybrids
was evaluated in vitro against three human cancer cell lines.
Standard protocols were adopted to examine the antiproliferative potential and mechanisms of compounds
. Western blot analysis was carried out on compound
.
Compounds
demonstrated in vitro antiproliferative activity in the range of 22.6-97.8%, with compounds
and
being the most active antiproliferative compounds with IC
values of 1.69 and 1.91 µM, which is fivefold and fourfold more potent than sunitinib (IC
=8.11 µM), respectively. Compound
was selected for in-depth pharmacological testing to understand its possible mechanism of antiproliferative activity. It caused a lengthening of the G1 phase and a reduction in the S and G2/M phases of the cell cycle and had an IC
value of 10.4 μM with the resistant NCI-H69AR cancer cell line. Moreover, compound
significantly decreased the amount of phosphorylated Rb protein in a dose-dependent fashion, which was confirmed via Western blot analysis.
The current investigation highlighted the potential antiproliferative activity of compounds
as well as the antiproliferative profile of compound
. These compounds can be harnessed as new lead antiproliferatives in the preclinical studies of cancer chemotherapy.