Synthesis and Anticancer Activity of Novel Derivatives of α,β‐Unsaturated Ketones Based on Oleanolic Acid: in Vitro and in Silico Studies against Prostate Cancer Cells

Abstract

Herein, new derivatives of α,β‐unsaturated ketones based on oleanolic acid (4a‐i) were designed, synthesized, characterized, and tested against human prostate cancer (PC3). According to the in vitro cytotoxic study, title compounds (4a‐i) showed significantly lower toxicity toward healthy cells (HUVEC) in comparison with the reference drug doxorubicin. The compounds with the lowest IC50 values on PC3 cell lines were 4b (7.785 µM), 4c (8.869 µM), and 4e (8.765 µM). The results of the ADME calculations showed that the drug‐likeness parameters were within the defined ranges according to Lipinski’s and Jorgensen's rules. For the most potent compounds 4b, 4c, and 4e, a molecular docking analysis using the induced fit docking (IFD) protocol was performed against three protein targets (PARP, PI3K, and mTOR). Based on the IFD scores, compound 4b had the highest calculated affinity for PARP1, while compound 4c had higher affinities for mTOR and PI3K. The MM‐GBSA calculations showed that the most potent compounds had high binding affinities and formed stable complexes with the protein targets. Finally, a 50 ns molecular dynamics simulation was performed to study the behavior of protein target complexes under in silico physiological conditions.

4‐Furfuryloxymethyl‐1,2,3‐triazol‐1‐yl‐acetohydrazide Hybrids as Cholinesterase and Carbonic Anhydrase Inhibitors: Synthesis, Characterization and Comprehensive Biological Activity Studies

“…The binding energy, represented by the IFD Score, was computed using standard parameters to produce 20 poses for each molecule through Glide XP docking. Subsequently, a comprehensive visual assessment was conducted for the generated poses in each protein‐ligand complex [54,62] …”

“…The in silico ADME properties of the selected compounds were performed utilized the QikProp panel of Maestro 13.5. QikProp provides values that compare the properties of new molecules to 95 % of known drugs [54,62] …”

“…Subsequently, a comprehensive visual assessment was conducted for the generated poses in each protein-ligand complex. [54,62]…”

“…QikProp provides values that compare the properties of new molecules to 95 % of known drugs. [54,62]…”

Synthesis of Sorafenib−Ruthenium Complexes, Investigation of Biological Activities and Applications in Drug Delivery Systems as an Anticancer Agent

“…The methods previously published by our research group were used to perform glide docking and induced fit docking. , The ligands that were prepared underwent docking with the receptors using the Induced Fit Docking (IFD) protocol in Schrödinger Release 2023-1. The IFD protocol, integrated into the Schrödinger suite, employs Glide (Schrödinger, LLC, New York, NY).…”