RESUMEN
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 inâ 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±68.87â nM against cytosolic hCA I isoform associated with epilepsy, and 28.82±14.26-153.27±55.80â 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.
Asunto(s)
Antineoplásicos , Nitroimidazoles , Estructura Molecular , Relación Estructura-Actividad , Simulación del Acoplamiento Molecular , Anhidrasa Carbónica I , Anhidrasa Carbónica II , Hidrazonas/farmacología , Inhibidores de Anhidrasa Carbónica/química , Isoformas de Proteínas/metabolismo , Antineoplásicos/química , Imidazoles/farmacologíaRESUMEN
In this study, we report a combined experimental and theoretical study on 3,5-bis(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbothioic O-acid (C18H18N2O3S) molecule. The compound crystallizes in the trigonal space group R-3 with a=b=27.7151(12) Å, c=12.4866(6) Å, α=ß=90.0°, γ=120.0° and Z=18. The crystal packing is stabilized by O-Hâ¯O and O-Hâ¯S intermolecular hydrogen bonds. These hydrogen bond interactions are also proved by NBO analysis. A detailed spectroscopic investigation is performed by the application of FT-IR and FT-NMR in addition to the theoretical approaches. Small energy gap between the frontier molecular orbitals is responsible for the nonlinear optical activity of the title molecule.