Targeting Colon Cancer Cells with Pyrazino-Imidazolinone Derivatives: Synthesis,Molecular Docking,and in Vitro Evaluation of Anti-Proliferative and Pro-Apoptotic Activities |
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Authors: | Nazia Tambat Pranav Tambe Amin Shaikh Kounsar N Shiekh Leonhard H F Köhler Rainer Schobert Bernhard Biersack Khursheed Ahmed |
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Institution: | 1. Advanced Scientific Research Laboratory (ASR-Lab.), Department of Chemistry, MCE Society's, Abeda Inamdar Senior College, Azam Campus, Pune, 411001 India;2. Organic Chemistry Laboratory, University Bayreuth, Universitätsstrasse 30, 95440 Bayreuth, Germany. |
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Abstract: | We report the synthesis, spectroscopic characterization, molecular docking and biological evaluation of nine pyrazino-imidazolinone derivatives. These derivatives were evaluated for their anticancer activity against three cancer cell lines: 518A2 melanoma, HCT-116, and HCT-116 p53 knockout mutant colon carcinoma. The MTT assay was employed to assess their effectiveness. Among the nine compounds tested, four compounds (5 a, 5 d, 5 g, and 5 h) exhibited promising antiproliferative activity specifically against HCT-116 p53-negative cells (IC50 0.23, 0.20, 2.07 and 58.75 μM, respectively). Interestingly, treatment with the 3,4-dimethoxyphenyl derivative 5a resulted in a significant increase (199 %) in caspase activity in HCT-116 p53-negative cells compared to untreated cells while the bromo-pyrazine derivative 5d demonstrated (190 %) increase. These findings suggest that compounds 5a and 5 d induce p53-independent apoptotic cell death. Additionally, in silico molecular docking studies with EGFR and tyrosinase proteins indicated that compounds 5 d and 5 e have the potential to bind to important anticancer drug targets. |
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Keywords: | antioxidant activity anticancer activity imidazolinone molecular docking pyrazine |
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