Anti-proliferative and ADMET screening of novel 3-(1H-indol-3-yl)-1, 3-diphenylpropan-1-one derivatives

Abstract

Cancer tends to be one of the major diseases in the present century affecting global population, and proliferation of cancerous cells needs to be eliminated as the cell growth is uncontrolled. In this present study, a series of facile, high yielding 3-(1H-indol-3-yl)-1, 3-diphenylpropan-1-ones 3(a-j) was designed, synthesized and evaluated for anti-proliferative activity against different human cancer cell lines; MCF-7 (breast cancer), K562 (leukemic cancer), HeLa (cervical cancer), Colo205 (colorectal adreno carcinoma), HepG2 (Hepato cellular carcinoma) cell lines. The compounds 3a, 3c, 3d, 3e, 3f, 3g and 3j exhibited an average inhibition of 35% against Hepatocellular Carcinoma (Hepg2) cell lines whereas, compounds 3a, 3c, 3d and 3e exhibited 33, 31, 35 and 33% inhibition, respectively, against HeLa cells at 10 μm concentrations. Doxorubicin was employed as a positive control. The ADME-TOX data was obtained by subjecting the molecules in silico to quantitatively predict the physicochemical properties. The structure of the title compounds were established by IR, 1 H NMR, 13 C NMR and Mass analysis.

Synthesis, antimicrobial, antioxidant, and ADMET studies of quinoline derivatives

“…The QSAR parameters are employed to optimize the molecular descriptors. The properties help to understand physicochemical and pharmacokinetics of their potentiality for ADME (Absorption, Distribution, Metabolism, Excretion) Toxicity [29][30][31][32][33][34][35]. The study enables the evaluation of biologically active and inactiveness of molecules, undesirable functional groups.…”

“…The study enables the evaluation of biologically active and inactiveness of molecules, undesirable functional groups. The Plog BB, log HIA, Caco-2 cell permeability (PCaco), Log pGI, Log Papp, and aqueous solubility (Plog S) help to know to understand the metabolism of active compounds [29][30][31][32][33][34][35]. The study also helps to envisage the toxic effect of different routes of drug administration.…”

Antiproliferative, Adme and Potential in Silico G6pdh Inhibitory Activity of Novel 2-(1-Benzofuran-2-Yl)-4-(5-Phenyl-4h-1, 2, 4-Triazol-3-Yl) Quinoline Derivatives

“…The antiproliferative activity of synthesized compounds was carried against five different cancer cell lines using doxorubicin as a positive control by MTT assay [11,12] (table 2). The cells lines were obtained from the Department of National Centre of Cell Sciences, Pune, India, and were cultured at a seeding density of 0.2 × 106 in DMEM/RPMI medium supplemented with 100 U/ml penicillin, 10% FBS and 100 g/ml streptomycin, respectively and maintained in a humidified atmosphere with 5% CO2…”

“…The in vitro antiproliferative activity of synthesized compounds 3(am) were determined by literature method [11,12]. Table 2 and fig.…”

“…Keeping in view of the above-mentioned facts, and in continuation of our research on coupled heterocycles [10,11], for biological evaluation, we focused on the synthesis of structurally distinct novel 2-(1-benzofuran-2-yl)-4-(5-phenyl-4H-1, 2, 4-triazol-3-yl) quinoline derivatives 3(a-m), for in vitro antiproliferative study on different cancer cell lines viz. MCF-7 (breast cancer), K562 (leukemic cancer), HeLa (cervical cancer), Colo205 (colorectal adenocarcinoma) and HepG2 (Hepatocellular carcinoma) by MTT assay [11,12]. The in silico molecular docking analysis was conducted to identify the binding ability of the ligands 3(a-m) with glucose-6-phosphate dehydrogenase (G6PDH) [13] to correlate with their in vitro antiproliferative activity as overexpression of G6PDH show resistance to apoptosis and pro-survival role in cancer cells.…”