New 1,2,3-Triazole-Coumarin-Glycoside Hybrids and Their 1,2,4-Triazolyl Thioglycoside Analogs Targeting Mitochondria Apoptotic Pathway: Synthesis, Anticancer Activity and Docking Simulation (original) (raw)
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Molecules
This study represents the design and synthesis of a new set of triazole-coumarin-glycosyl hybrids and their tetrazole hybrid analogues possessing various sugar moieties and modified analogues. All the newly synthesized derivatives were screened for their cytotoxic activities against a panel of human cancer cell lines. The coumarin derivatives 10, 13 and 15 derivatives revealed potent cytotoxic activities against Paca-2, Mel-501, PC-3 and A-375 cancer cell lines. These promising analogues were further examined for their inhibitory assessment against EGFR, VEGFR-2 and CDK-2/cyclin A2 kinases. The coumarin-tetrazole 10 displayed broad superior inhibitory activity against all screened enzymes compared with the reference drugs, erlotinib, sorafenib and roscovitine, respectively. The impact of coumarin-tetrazole 10 upon cell cycle and apoptosis induction was determined to detect its mechanism of action. Additionally, it upregulated the levels of casp-3, casp-7 and cytochrome-c proteins an...
Synthesis of Novel 1,2,4-Triazolyl Coumarin Derivatives as Potential Anticancer Agents
Journal of Chemistry
A series of novel coumarin derivatives carrying 1,2,4-triazole or 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole moieties were prepared and evaluated in vitro as anticancer in the human colon cancer (HCT116) cell line. The derivatives 4c and 8c exhibited marked anticancer activity with IC50 values 4.363 and 2.656 µM, respectively. The molecular docking studies suggested possible interaction with tyrosine kinases (CDK2).
Molecules, 2012
We report here on the synthesis and in vitro anti-tumor effects of a series of novel 1,2,4-triazole (compounds 3-6), 4,5-dicyanoimidazole (compound 7), and purine (compounds 8-13) coumarin derivatives and their acyclic nucleoside analogues 14-18. Structures of novel compounds 3-18 were deduced from their 1 H-and 13 C-NMR and corresponding mass spectra. Results of anti-proliferative assays performed on a panel of selected human tumor cell lines revealed that compound 6 had moderate cytostatic activity against the HeLa cell line (IC 50 = 35 µM), whereas compound 10 showed moderate activity against the HeLa (IC 50 = 33 µM), HepG2 (IC 50 = 25 µM) and SW620 (IC 50 = 35 µM) cell lines. These compounds showed no cytotoxic effects on normal (diploid) human fibroblasts.
ACS Chemical Biology, 2017
Mitochondria imparts crucial role in the regulation of programmed cell death, reactive oxygen species (ROS) generation besides serving as a primary energy source. Mitochondria appeared as an important target for therapy of cancer due to its significant contribution in 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 standard drug Doxorubicin in-vitro and in-vivo studies. MCS5 displayed an IC 50 value of 1.92 µM and induced apoptosis in Cal72 (human osteosarcoma cell line) cells by targeting mitochondrial pathway. This compound arrested G2/M phase of cell cycle, induced ROS production and mitochondrial potential collapse in Cal72 cells. MCS-5 displayed excellent anticancer activity in 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, 2DG optical probe guided study clearly evokes that MCS-5 remarkably reduced tumor metastasis in 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 for the management of cancer in the future. ACS Paragon Plus Environment ACS Chemical Biology 3 predominantly responsible for cancer mortality. 2 Treatment of cancer relies heavily on conventional therapies such as chemotherapy, radiotherapy, surgical removal as well as immunotherapy. 3-4 Since long time, widespread efforts have been done to counteract malignancies and in result various anticancer agents have been discovered. 5-8 However, clinically running anticancer drugs exert dreadful side effects, including cytotoxicity against normal cells. 9-10
Heliyon, 2020
The current study demonstrates the synthesis of coumarin-triazole hybrids 8 (a-e) in four steps starting from substituted salicylaldehyde 1 (a-e), and diethyl malonate 2. The spectroscopic studies provide the structure proofs of the new compounds, and the molecular structure of an intermediate 3a by crystallographic studies. The crystal structure analysis revealed the C-H...O, C-H... π, CO ...π and π...π molecular interactions. Further, the intermolecular interactions were quantified using Hirshfeld surface analysis and the DFT method B3LYP functional with 6-311þþ G (d,p) basis set was employed to optimize the molecular geometry. The synthesized new coumarintriazole hybrids, 8 (a-e) were screened for their α-amylase inhibitory potentials, and the results suggest that amongst the series, compounds 8c, and 8e show the promising inhibition of the enzyme, and might act as lead molecules for anti-diabetic activities. To understand the mode of action in silico molecular docking and ADME screening were performed.
Biointerface Research in Applied Chemistry, 2021
1,2,3-triazole skeleton is a privileged building block for the discovery of new promising anticancer agents. In this report, new 1,4-disubstituted 1,2,3-triazoles with the bioisoster triazole moiety were straightforwardly prepared under copper-catalyzed azide-alkyne [3+2] cycloaddition reactions (CuAAC) regime using a variety of both functional organic azides and terminal alkynes. The resulting functional 1,4-disubstituted 1,2,3-triazole compounds were fully characterized and subsequently tested for their antiproliferative activity against four different cancer cell lines. The cytotoxicity tests carried out with these 1,2,3-triazole derivatives show average IC50 values ranging from 15 to 50 µM by comparison with the standard reference drug, namely doxorubicin. The phosphonate 1,2,3-triazole derivative was found to exhibit the best antiproliferative activity among the studied compounds against the HT-1080 cell lines. It was chosen to evaluate its mode of action in these cancer cell l...