Mitochondria impart a crucial role in the regulation of programmed cell death and
reactive oxygen species (ROS) generation, besides serving as a primary energy source. Mitochondria appeared as an important target for the
therapy of
cancer due to their significant contribution to cell survival and death. Here, we report the design and synthesis of a novel series of
triazole-
piperazine hybrids as potent
anticancer agents. MCS-5 emerged as an excellent
anticancer agent which showed better anticancer activity than the standard
drug doxorubicin in in vitro and in vivo studies. MCS-5 displayed an IC50 value of 1.92 μM and induced apoptosis in Cal72 (human
osteosarcoma cell line) cells by targeting the mitochondrial pathway. This compound arrested the G2/M phase of the cell cycle and induced ROS production and mitochondrial potential collapse in Cal72 cells. MCS-5 displayed excellent anticancer activity in the Cal72 xenograft nude mice model, where it significantly reduced
tumor progression, leading to enhanced life span in treated animals compared to control and
doxorubicin treated animals without exerting noticeable toxicity. In addition, a 2DG optical probe guided study clearly evoked that MCS-5 remarkably reduced
tumor metastasis in the Cal72 xenograft nude mice model. These results indicate that MCS-5 appeared as a novel chemical entity which is endowed with excellent in vitro as well as in vivo anticancer activity and may contribute significantly to the management of
cancer in the future.