New imidazole-2-ones and their 2-thione analogues as anticancer agents and CAIX inhibitors: Synthesis, in silico ADME and molecular modeling studies.

The present study involves the synthesis of a series of new imidazole-2-ones derivatives and their 2-thione analogs using conventional heating and the environmentally friendly benign technique, the microwave technique. Structure of the compounds was well elucidated by considering the data of both elemental and spectral analyses. The obtained data and theoretical values of the synthesized molecules correlated with the proposed molecular structure. Moreover, all the synthesized compounds were evaluated in vitro for antitumor activity against HCT-116 and HeP2 human cancer cell panels and assessed as selective carbonic anhydrase IX isozyme (CA9/CAIX) inhibitors, thereby providing useful preliminary evidence for drug development. In addition, computational techniques were used to investigate the molecular and electronic characteristics of the investigated organic compounds. The 4b compound exhibited the best quantum chemistry features, as the highest occupied molecular orbital, softness, energy gap, and dipole moment, indicating the highest biological activity. This was supported by the experimental findings. Moreover, the in silico evaluation of drug candidates was also investigated. Thereafter, the anticancer activity of the most reactive candidate was studied via molecular docking to determine the types of interactions between this molecule and CAIX. According to the docking experiments, the 4b molecule generates five hydrogen bond interactions with active amino acid residues, Gln 92, Gln 67, and Thr 200.

Osthole extracted from a citrus fruit that affects apoptosis on A549 cell line by histone deacetylasese inhibition (HDACs).

This study aims to investigate the interactions between osthole extracted from Egyptian citrus fruits as HDACs inhibitor by theoretical study and practically. Besides, osthole was assed as anti-cancer activity. In this study, osthole was extracted from the Egyptian citrus fruit and was characterized. The role of osthole as in vitro inhibitor of HDACs was estimated and evaluated the antitumor activity against human lung cancer cells (A549), Caspase-9 activity was detected. The results obtained from GC-MS indicate that the grapefruit showed the highest osthole concentration compared to the other citrus fruits. Moreover, the grapefruit osthole competitively inhibits HDACs. The inhibition constant value, (Ki=3.36 mM), indicates that osthole exerts an inhibitory effect upon HDACs activity. In vitro study of osthole could inhibit the growth of A549 cells that depend on time and concentration. It also induces apoptosis and causes an increase of caspase-9 by osthole. In conclusion, grapefruit osthole could induce the apoptosis in A549 lung cancer cells by inhibiting the histone deacetylase.

Molecular docking, molecular modeling, vibrational and biological studies of some new heterocyclic α-aminophosphonates.

A new diphenyl (aryl) (Ǹ-quinazolin-4-yl-hydrazino) methylphosphonates 3a-3d was synthesized via anhydrous zinc chloride catalyzed Kabachnic-Fields reaction. The structure of the synthesized compounds was confirmed by elemental analysis, FT-IR, 1H NMR, 13C NMR, 31P NMR and MS spectral data. The synthesized compounds showed significant antimicrobial and also remarkable cytotoxicity anticancer activities against breast carcinoma cell line (MCF7). The quantum chemical calculations were performed using density functional theory (DFT) to study the effect of the changes of molecular and electronic structures on the biological activity of the investigated compounds. Also, NBO and theoretical FT-IR were calculated. The experimental results were validated by molecular docking simulation of compound 3b in the active pocket of the enzyme. The important binding interactions with the key residues in the active site were revealed. A good correlation was found between the quantum chemical parameters and experimental data.