IN SILICO SEARCH OF POTENT PHYTOECDYSTEROIDS TARGETING DIFFERENT CANCER PROTEINS
DOI:
https://doi.org/10.3126/jist.v31i1.86921Keywords:
Binding affinity, Cancer, Chemotherapy, Molecular docking , PhytoecdysteroidsAbstract
Cancer remains a major global health challenge, and existing drugs have limited efficacy and adverse side effects. Key molecular regulators such as PARP1, ABL1, and CDK2 represent attractive targets for developing safer and more effective anticancer agents. MDA468 (Breast cancer), HCT-116 (Colon Cancer), CCRF (Leukemia), MDA-MB-435 (Melanoma), HOP-18 (non-small lung cancer), SKOV3 (Ovarian cancer), DU-145(Prostate cancer), and SN12K1 (Renal cancer) are cell lines studied in this paper. 216 phytoecdysteroids were computationally screened against these targets using molecular docking, ADMET profiling, and molecular dynamics simulations (MDS). Among them, Ecdysterone 22-benzoate 25-O-β-D-glycoside (PES 1) exhibited strong binding affinities of –11.3 kcal/mol (3L3M) and –9.1 kcal/mol (8H7H), while E-2-Deoxy-20-hydroxyecdysone 3-[4-(1-β-D-glucopyranosyl)]-caffeate (PES 44) demonstrated affinities of –9.3 kcal/mol (2A0C) and –9.2 kcal/mol (8H7H). Both complexes maintained RMSD values below 2 Å, and ADMET predictions further indicated favourable pharmacokinetic properties and low predicted toxicity. These findings suggest that PES 1 and PES 44 are promising phytoecdysteroid-based inhibitors with potential anticancer activity, warranting further extended simulations and experimental validation for their development into effective and safer anticancer therapeutics.
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