Cytotoxic Activity and Docking Studies of 2-arenoxybenzaldehyde N-acyl Hydrazone and 1,3,4-Oxadiazole Derivatives against Various Cancer Cell Lines

Abstract

To understand whether previously synthesized novel hydrazone and oxadiazole derivatives have promising anticancer effects, docking studies and in vitro toxicity assays were performed on A-549, MDA-MB-231, and PC-3 cell lines. The antiproliferative properties of the compounds were investigated using molecular docking experiments. Each compound’s best-docked poses, binding affinity, and receptor-ligand interaction were evaluated. Compounds’ molecular weights, logPs, TPSAs, abilities to pass the blood-brain barrier, GI absorption qualities, and CYPP450 inhibition have been given. When the activities of these molecules were examined in vitro, for the A-549 cell line, hydrazone 1e had the minimum IC50 value of 13.39 μM. For the MDA-MB-231 cell line, oxadiazole 2l demonstrated the lowest IC50 value, with 22.73 μM. For PC-3, hydrazone 1d showed the lowest C50 value of 9.38 μM. The three most promising compounds were determined as compounds 1e, 1d, and 2a based on their minimum IC50 values, and an additional scratch assay was performed for A-549 and MDA-MB-231 cells, which have high migration capacity, for the three most potent molecules; it was determined that these molecules did not show a significant antimetastatic effect.

Novel N-Acyl Hydrazone Compounds as Promising Anticancer Agents: Synthesis and Molecular Docking Studies

“…The formation of the intermediates 3a-e was confirmed by the molecular ion peak observed by the GC–MS spectrum. Finally, compounds 3a-e were reacted with various aldehydes ( p -anisaldehyde, 2-furaldehyde, and isovaleraldehyde) in dimethylformamide (DMF) in the refluxing condition to generate δ-ketal N -acyl hydrazones 4a-e , 5a-e , and 6a-e in 51–95% isolated yields. , Then, the hydrolysis reaction of 4a was investigated in the presence of several acid catalysts and solvents in order to optimize reaction conditions. The results are shown in Table .…”

“…General Procedure for the Synthesis of δ-Ketal N-Acyl Hydrazones (4a-e, 5a-e, 6a-e). 56,57 The δ-ketal hydrazide 3a-e (1 mmol) and aldehyde (anisaldehyde, furfural, or isovaleraldehyde) (2 mmol) in DMF (2 mL) were added to a reaction flask, and then the mixture was heated to reflux. The reaction progress was monitored by TLC (eluent: hexane:E-tOAc (1:1).…”

Synthesis of an aggregation-induced emission-based fluorescent probe based on rupestonic acid

“…The Janus kinase 2 protein was chosen to investigate rupestonic acid and the probe's anticancer activities on breast cancer considering the protein was targeted by many anti-cancer drugs to produce their response. 47,48…”

“…The Janus kinase 2 protein was chosen to investigate rupestonic acid and the probe's anticancer activities on breast cancer considering the protein was targeted by many anti-cancer drugs to produce their response. 47,48 Rupestonic acid and the probe exhibited hydrogen bond with ASP939 and ARG980 residues, respectively (Fig. 5a and b).…”

“…49 Meanwhile, the published X-ray crystallographic structure of MDA-MB-231 polymerase (PDB ID: 3KRR) was downloaded from the PDB database (https://www.rcsb.org/structure/ 3KRR). 47,48 Protein was prepared using the Protein Preparation Wizard tool in maestro molecular modeling soware (Schrodinger Release 2018). 50 Finally, molecular docking was carried out by running Ligand Docking tool.…”