Synthesis and evaluation of anticancer and antiobesity activity of 1-ethoxy carbonyl-3,5-bis (3'-indolyl methylene)-4-pyperidone analogs.

A series of eleven novel bisindole derivatives were synthesized and screened for anticancer and antiobesity potentials in in vitro mode. The reaction of 1-ethoxy carbonyl 4-pyperidone 1a with indole-3-carboxaldehyde 1b in presence of catalytic amount of piperidine gave 2 which was N-alkylated with different benzyl halides in the presence of potassium carbonate to afford compounds 3a-3k in quantitative yields. Among the compounds tested for anticancer activity against different human cancer cell lines, 3f significantly inhibited HepG2 cell line (IC50 7.33 µM) when compared with standard doxorubicin (IC50 10.15 µM). Compounds 3e (IC50 2.75 µM), 3f (IC50 4.21 µM) and 3i (IC50 15.98 µM) showed better activity than the standard curcumin (IC50 23.54 µM) against A549 cell line. Also, among the synthesized compounds, 3g (IC50 14.89 µM), 3c (IC50 56.41 µM) and 3i (IC50 30.88 µM) have potentially inhibited enzyme lipase when compared to standard Orlistat (IC50 62.25 µM). In in silico docking assays, piperidones 3e, 3f, 3i, 3c and 3a showed higher binding affinity towards anti-cancer target of A549 (3e: -11.1, 3f: -10.3, 3c: -11.3, 3i: -11.2 kcal/mol), HepG2 (3f: -10.5 kcal/mol), HeLa (3d: -10.0 kcal/mol) and SKOV3 (3f: -8.4 kcal/mol) cell lines better than standard drug doxorubicin. Docking to lipase protein for compounds 3i, 3g and 3c showed scores of -11.1, -10.7 and -10.5 kcal/mol when compared to that of standard drug Orlistat with -6.9 kcal/mol.

Synthesis, docking and ADMET studies of novel chalcone triazoles for anti-cancer and anti-diabetic activity.

A series of novel chalcone-triazole derivatives were synthesized and screened for in vitro anticancer activity on the human cancer cell lines IMR32 (neuroblastoma), HepG2 (hepatoma) and MCF-7 (breast adenocarcinoma), DU-145 (prostate carcinoma), and A549 (lung adenocarcinoma). Among the tested compounds, 4r showed the most promising anticancer activity in all the cell lines whereas, compounds 4c (IC50 65.86 µM), 4e (IC50 66.28 µM), 4o (IC50 35.81 µM), 4q (IC50 50.82 µM) and 4s (IC50 48.63 µM) showed better activity than the standard doxorubicin (IC50 69.33 µM) in A549 cell line alone. Rat intestinal α-glucosidase inhibitory activity of the synthesized derivatives showed 4m (IC50 67.77 µM), 4p (IC50 74.94 in µM) and 4s (IC50 102.10 µM) as most active compared to others. The in silico docking of synthesized derivatives 4a-4t with DNA topoisomerase IIα revealed the LibDock score in the range of 71.2623-118.29 whereas, compounds 4h, 4m, 4p and 4s with docking target α-glucosidase were in the range of 100.372-107.784.

Synthesis of cyclic 1,9-acetal derivatives of forskolin and their bioactivity evaluation.

A new series of 1,9-acetals of forskolin were synthesized by treating with aromatic and aliphatic aldehydes using Ceric ammonium nitrate as catalyst and evaluated for anticancer and α-glucosidase inhibition activities. Among the synthesized compounds 2a, 2b and 3a showed potential cytotoxic activity towards human cancer cell lines MCF-7 (Human Breast Adenocarcinoma), MDA-MB (Human Breast Carcinoma), HeLa (Human Cervix Adenocarcinoma), A498 (Human Kidney Carcinoma), K562 (Human Erythromyeloblastoid leukemia), SH-SY5Y (Human Neuroblastoma), Hek293 (Human Embryonic Kidney) and WRL68 (Human Hepatic) with IC50 values ranging between 0.95 and 47.96 µg/ml. Osmotic fragility test revealed compound 3a as non-toxic to human erythrocytes at the tested concentrations of 50 and 100 µg/ml. Compounds 1g (IC50 value 0.76 µg/ml) and 1p (IC50 value 0.74 µg/ml) significantly inhibited α-glucosidase in in vitro system. In silico based docking, ADME and toxicity risk assessment studies also showed discernible α-glucosidase activity for compounds 1g, 1p compared to standard acarbose.