Chalcones bearing nitrogen-containing heterocyclics as multi-targeted inhibitors: Design, synthesis, biological evaluation and molecular docking studies.

In this work, a series of chalcones (1a-d, 2a-d, 3a-d, 4a-d, and 5a-d) were designed and synthesized by Claisen-Schmidt condensation. Also, their chemical structures were elucidated using UV-Vis, FT IR, 1 H NMR, 13 C NMR, MS spectral data, and elemental analyses. Subsequently, the anticholinesterase, tyrosinase, urease inhibitory activities and antioxidant activities of all chalcones were evaluated. The inhibitory potential of all chalcones in terms of IC50 value was observed to range from 7.18 ± 0.43 to 29.62 ± 0.30 µM against BChE by comparing with Galantamine (IC50 46.06 ± 0.10 µM) as a reference drug. Also, compounds 2c, 3c, 4c, 4b, and 4d exhibited high anticholinesterase activity against both AChE and BChE enzymes. The tyrosinase inhibitory activity results revealed that three compounds (IC50 1.75 ± 0.83 µM for 2b, IC50 2.24 ± 0.11 µM for 3b, and IC50 1.90 ± 0.64 µM for 4b) displayed good inhibitory activity against tyrosinase compared with kojic acid (IC50 0.64 ± 0.12 µM). In addition, other different three chalcones (IC50 22.34 ± 0.25 µM for 2c, IC50 20.98 ± 0.08 µM for 3c, and IC50 18.26 ± 0.13 µM for 4c) showed excellent inhibitory activity against the urease by comparing with thiourea (IC50 23.08 ± 0.19 µM). Compounds 3c and 4c showed the best potency in all antioxidant activity tests. In light of these findings, the structure-activity relationship for compounds was also described. Furthermore, molecular modeling studies, including molecular docking, absorption, distribution, metabolism, excretion, and toxicity (ADMET), and pharmacophore analyses of compounds, gave important information about the interactions and drug-likeness properties. As a result, all chalcones exhibited suitable ADMET findings, predicting good oral bioavailability.

Synthesis, Biological Activity Evaluation and Molecular Docking of Imidazole Derivatives Possessing Hydrazone Moiety.

In an attempt to identify potential active anticancer agents with low cytotoxic properties and CA inhibitors, a new series of hybrid compounds incorporating imidazole ring and hydrazone moiety as part of their structure were synthesized by aza-Michael addition reaction followed by intramolecular cyclization. The structure of synthesized compounds was elucidated using various spectral techniques. Synthesized compounds were evaluated for their in vitro anticancer (prostate cell lines; PC3) and CA inhibitory (hCA I and hCA II) activity. Among them, some compound displayed remarkable anticancer activity and CA inhibitory activity with Ki values in range of 17.53±7.19-150.50±68.87 nM against cytosolic hCA I isoform associated with epilepsy, and 28.82±14.26-153.27±55.80 nM against dominant cytosolic hCA II isoforms associated with glaucoma. Furthermore, the theoretical parameters of the bioactive molecules were calculated to establish their drug-likeness qualities. The proteins used for the calculations are prostate cancer protein (PDB ID: 3RUK and 6XXP). ADME/T analysis was carried out to examine the drug properties of the studied molecules.