Green Synthesis and Anticancer Potential of 1,4-Dihydropyridines-Based Triazole Derivatives: In Silico and In Vitro Study.
Sabera BijaniDanish IqbalSheefa MirzaVicky JainSadaf JahanMohammed AlsaweedYahya MadkhaliSuliman Abdallah AlsagabySaeed S BanawasAbdulrahman AlgarniFaris A AlrumaihiRakesh M RawalWael AlturaikiAnamik ShahPublished in: Life (Basel, Switzerland) (2022)
A library of 1,4-dihydropyridine-based 1,2,3-triazol derivatives has been designed, synthesized, and evaluated their cytotoxic potential on colorectal adenocarcinoma (Caco-2) cell lines. All compounds were characterized and identified based on their 1 H and 13 C NMR (Nuclear Magnetic Resonance) spectroscopic data. Furthermore, molecular docking of best anticancer hits with target proteins (protein kinase CK2α, tankyrase1, and tankyrase2) has been performed. Our results implicated that most of these compounds have significant antiproliferative activity with IC 50 values between 0.63 ± 0.05 and 5.68 ± 0.14 µM. Moreover, the mechanism of action of most active compounds 13ab' and 13ad' suggested that they induce cell death through apoptosis in the late apoptotic phase as well as dead phase, and they could promote cell cycle arrest at the G2/M phase. Furthermore, the molecular docking study illustrated that 13ad' possesses better binding interaction with the catalytic residues of target proteins involved in cell proliferation and antiapoptotic pathways. Based on our in vitro and in silico study, 13ad' was found to be a highly effective anti-cancerous compound. The present data indicate that dihydropyridine-linked 1,2,3-triazole conjugates can be generated as potent anticancer agents.
Keyphrases
- molecular docking
- cell death
- cell cycle arrest
- magnetic resonance
- molecular dynamics simulations
- cell proliferation
- protein kinase
- pi k akt
- squamous cell carcinoma
- magnetic resonance imaging
- electronic health record
- machine learning
- computed tomography
- risk assessment
- cell cycle
- mass spectrometry
- rectal cancer
- data analysis
- crystal structure