Comprehensive molecular docking, cytotoxicity, and ADMET analysis of documented curcuminoid derivatives on the A549 cell line Mustafa Q. Alderawy, Mustafa M. AL-Hakiem, Reham A. AL-Anssari, Rita S. Elias Pharmacia, 2025 Various novel curcuminoids (1–7) and pyrazole derivatives of curcuminoids (8–14) were synthesized and characterized using spectrum analysis. The compounds produced were evaluated for antiproliferative effects against the A549 lung cancer cell line. Compound 2 exhibited notable cytotoxicity at 10.38 μg/mL, whereas compounds 4, 5, and 7 showed considerable cytotoxicity, with IC₅₀ concentrations of 47.1, 23.4, and 82.4 μg/mL, respectively. Conversely, the other synthesized compounds exhibited only modest cytotoxicity. Moreover, in silico molecular docking analyses of EGFR (PDB ID: 4HJ0) demonstrated that compounds 2 and 6 displayed the lowest binding energies, −11.52 kcal/mol and −11.47 kcal/mol, respectively, indicating a higher affinity for the active pocket of the receptor, characterized by robust hydrogen bond interactions. Compound 12 had the highest binding energy (−8.42 kcal/mol) and the weakest affinity (KI = 670.04 nM). SwissADME analysis revealed satisfactory drug-likeness among all compounds, with no violations of Lipinski’s rules and modest synthetic accessibility. ProTox-II indicated tolerable oral toxicity (LD₅₀: 1300–4000 mg/kg), although elevated immunotoxicity scores imply the need for additional safety assessment. These data identify compound 2 as a promising candidate for future optimization and preclinical development.
Synthesis, Characterization, and Antibacterial Activity Study of Novel Curcuminoids Derivatives Mustafa M. AL-Hakiem, Mustafa Q. Alderawy, Riham Adnan, Rita S Elias Iraqi Journal of Pharmaceutical Sciences, 2024 Curcumin is a well-known compound with broad spectrum biological activities, but unfortunately rapid degradation properties and low bioavailability. Therefore, several attempts have been made to overcome these obstructions through chemical modifications. This investigation aimed to prepare several curcuminoids and their pyrazole derivatives and study their antibacterial activity. Curcuminoids and their pyrazole derivatives were synthesized, and their Chemical structures were established from their mass, 1H NMR, and 13C NMR spectra, followed by an in vitro study of the antibacterial activity of these compounds against the gram-negative Escherichia coli and the gram-positive Staphylococcus aureus using disc diffusion method. No compound has recorded any activity against Escherichia coli, while compounds 1-9 have shown anti-staphylococcus activity, compounds 11-14 didn’t present any activity, and compound 10 shows activity at the lowest studied concentration only. These findings suggest that the pyrazole substitution on curcumin derivatives that do not bear an aromatic hydroxyl group would diminish their anti-staphylococcal activity. More antibacterial activity studies are suggested regarding compound 10 activity
Investigation of the antioxidant and antibacterial activity of novel quercetin derivatives Biointerface Research in Applied Chemistry, 2020 Our previous work involved the preparation and characterization of six quercetin derivatives, three of which were novel Schiff bases, while the fourth was a novel ionic salt of iodine. This study involved the investigation of the in vitro antioxidant activity against DPPH free radical as well as the in vitro antibacterial activity against Bacillus cereus, Salmonella spp., Escherichia coli and Staphylococcus aureus of quercetin and its 1-6 derivatives. The results revealed that all the studied quercetin derivatives had shown less antioxidant and antibacterial activity than quercetin itself, except that of compounds 3 and 4, which displayed an improvement in the antibacterial activity against Escherichia coli as compared to that of quercetin.
