Novel fused imidazotriazines acting as promising top. II inhibitors and apoptotic inducers with greater selectivity against head and neck tumors: Design, synthesis, and biological assessments

Understanding Cancer’s Defense against Topoisomerase-Active Drugs: A Comprehensive Review

“…Recently, some data have indicated that irinotecan may worsen hepatic oxidative stress by inducing the formation of ROS and lipid peroxides while simultaneously lowering GSH, superoxide dismutase (SOD), and catalase (CAT) in cancer cells [152]. As topo-active drugs decrease the level of GSH, newer derivatives with redox-sensitive targeted delivery which will maintain the GSH level in treated cancer cells are recommended to avoid drug resistance and desirable apoptotic cell death [153,154].…”

Repurposed organoselenium tethered amidic acids as apoptosis inducers in melanoma cancer via P53, BAX, caspases-3, 6, 8, 9, BCL-2, MMP2, and MMP9 modulations

“…68 At the end of the molecular docking process; the best pose for each compound (based on the score and binding interactions) was isolated and visualized to be compared to that of the co-crystallized inhibitor. 69 4.3.2. Physicochemical, ADME, and pharmacokinetic properties prediction.…”

Design and synthesis of novel chloropyridazine hybrids as promising anticancer agents acting by apoptosis induction and PARP-1 inhibition through a molecular hybridization strategy

“…A lot of targets, genes, and pathways have been identified to be effective for cancer treatment and this helped to introduce a lot of treatment options and therapies. [8][9][10] However, the problem of cancer resistance appeared to be a big challenge that caused a lot of therapeutic failures either conventional chemotherapy or targeted therapies (smart drugs). [11][12][13] This may be attributed to two mechanisms; the first one is the genetic changes existing before treatment which is considered to be the intrinsic or primary resistance.…”

“…Collectively, the previously mentioned mechanisms for cancer resistance are due to the genome's mutations of tumor cells and/or epigenetic modifications. 10,14,15 Apoptosis is a type of cellular death following a programmed mechanism through two major apoptotic pathways. 16 The first one is the intrinsic pathway which is initiated by various events inside cells like mitochondrial oxidative stress, however, the second one is the extrinsic pathway which is induced by external factors like tumor necrosis factor-α (TNF-α).…”

“…Collectively, the previously mentioned mechanisms for cancer resistance are due to the genome's mutations of tumor cells and/or epigenetic modifications. 10,14,15…”