title: Novel Triazole-Piperazine Hybrid Molecules Induce Apoptosis via Activation of the Mitochondrial Pathway and Exhibit Antitumor Efficacy in Osteosarcoma Xenograft Nude Mice Model.
abstract: 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 IC50value 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.
authors.affiliation: Bio-organic Chemistry Laboratory, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi , Delhi 110007, India.
authors.forename: Chandra Bhushan
authors.initials: CB
authors.lastname: Mishra
authors.affiliation: Laboratory of Animal Genetic Engineering and Stem Cell Biology, Department of Animal Biotechnology and Advance Next Generation Convergence, Faculty of Biotechnology, Jeju National University , Jeju-Do, Republic of Korea.
authors.forename: Raj Kumar
authors.initials: RK
authors.lastname: Mongre
authors.affiliation: Bio-organic Chemistry Laboratory, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi , Delhi 110007, India.
authors.forename: Shikha
authors.initials: S
authors.lastname: Kumari
authors.affiliation: Laboratory of Animal Genetic Engineering and Stem Cell Biology, Department of Animal Biotechnology and Advance Next Generation Convergence, Faculty of Biotechnology, Jeju National University , Jeju-Do, Republic of Korea.
authors.forename: Dong Kee
authors.initials: DK
authors.lastname: Jeong
authors.affiliation: Laboratory of Animal Genetic Engineering and Stem Cell Biology, Department of Animal Biotechnology and Advance Next Generation Convergence, Faculty of Biotechnology, Jeju National University , Jeju-Do, Republic of Korea.
authors.forename: Manisha
authors.identifier: 0000-0001-8942-0578
authors.initials: M
authors.lastname: Tiwari
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001859:Bone Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D051379:Mice; D008819:Mice, Nude; D008928:Mitochondria / Q000187:drug effects*; D009362:Neoplasm Metastasis / Q000517:prevention & control; D012516:Osteosarcoma / Q000473:pathology*; D010879:Piperazines / Q000737:chemistry* / Q000494:pharmacology*; D014230:Triazoles / Q000737:chemistry* / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D010879:Piperazines; D014230:Triazoles