Synthesis, in vitro biological evaluation and in silico docking studies of new quinazolin‐2,4‐dione analogues as possible anticarcinoma agents

Abstract

Today, cancer is considered as one of the major reasons of death in human beings worldwide. We reported herein the synthesis, anticancer activity, and in silico docking studies of a series of nine quinazolindione‐based scaffolds bearing pyrimidine, pyridine, pyran, and pyrazole moieties (1‐9) through Michael addition, Vilsmeier‐Haack, Claisen‐Schmidt, and nucleophilic addition reactions. The chemical structures of the newly prepared compounds were ascertained by means of their spectral analysis techniques like IR, 1H‐nuclear magnetic resonance (NMR), 13C‐NMR, mass spectroscopy, and elemental analysis. This work was conducted to investigate the implication of Rho7 protein in breast and hepatocellular cancer cells aggressively. MCF‐7 and HepG2 cells have been selected as models for the effect of protein expression on breast and hepatocellular cancers cell growth. All prepared compounds were biologically evaluated for their antiproliferative efficacy on hepatic cancer cell lines (HepG2) and breast cancer cell lines (MCF‐7); also, their effects on normal cell lines (BALB/3T3) were studied. Moreover, in silico molecular docking studies were studied for the compounds against the binding site of Homo sapiens Rho7 protein. The pharmacokinetic properties of the newer compounds were also evaluated using various computational tools. The compounds showed interesting interactions with satisfactory docking scores to the target Rho7; thus, they may act as promising potent drug candidates against cancer.

Synthesis, In Silico and In Vitro Assessment of New Quinazolinones as Anticancer Agents via Potential AKT Inhibition

“…The quinazoline derivatives have significant interaction poses with the modeled AKT1 through hydrogen bonds, π–π, π–cation, and π–σ interactions. Greater values of negative binding free energy ΔG b (reported in kcal/mol) indicate better matching between the ligand molecule and target [ 31 , 32 , 33 , 34 ]. The reference compound doxorubicin had the lowest binding free energy (ΔG b = −7.6 kcal/mol) and exhibited two π–π stacking with TRP191.…”

Homology Modeling and Virtual Screening Studies of Antigen MLAA-42 Protein: Identification of Novel Drug Candidates against Leukemia—An In Silico Approach

“…Molecular docking protocol is used to predict the preferred orientation of a ligand molecule to the target protein to form a stable complex [40,41]. e docking accuracy is determined by finding how closely the binding confirmation with Computational and Mathematical Methods in Medicine the lowest energy of the cocrystalized ligand molecule predicted by the object scoring function; G-score (Glide score) resembles an experimental binding modes determined by X-ray crystallographic technique [42].…”

Eco-Friendly Synthesis, Biological Evaluation, and In Silico Molecular Docking Approach of Some New Quinoline Derivatives as Potential Antioxidant and Antibacterial Agents

“…For complementing this way and in continuation of our search work (Abdelmonsef and Mosallam, 2020;Haredi Abdelmonsef et al, 2020;Noser et al, 2020;Rashdan et al, 2020;Shehadi et al, 2020; SCHEME 1 | Synthesis of quinoline derivative 5a-d under solvent-free conditions. SCHEME 2 | Synthesis of quinoline 6.…”

“…For complementing this way and in continuation of our search work ( Abdelmonsef and Mosallam, 2020 ; Haredi Abdelmonsef et al, 2020 ; Noser et al, 2020 ; Rashdan et al, 2020 ; Shehadi et al, 2020 ; Gomha et al, 2021 ), we decided to eco-friendly synthesize some quinoline scaffolds and test in vitro their antioxidant and antibacterial activity. Moreover, the compounds were docked into the binding sites of the target enzymes: human NAD (P)H dehydrogenase (quinone 1) and DNA gyrase, respectively.…”