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Synthesis and evaluation of anticancer and antiobesity activity of 1-ethoxy carbonyl-3,5-bis (3'-indolyl methylene)-4-pyperidone analogs.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2016 Mar 15; Vol. 26 (6), pp. 1633-1638. Date of Electronic Publication: 2016 Jan 28. - Publication Year :
- 2016
-
Abstract
- 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.<br /> (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Subjects :
- Anti-Obesity Agents chemistry
Antineoplastic Agents chemistry
Cell Line, Tumor
Cell Proliferation drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Enzyme Inhibitors chemical synthesis
Enzyme Inhibitors chemistry
Enzyme Inhibitors pharmacology
Humans
Lipase metabolism
Molecular Structure
Piperidones chemistry
Structure-Activity Relationship
Anti-Obesity Agents chemical synthesis
Anti-Obesity Agents pharmacology
Antineoplastic Agents chemical synthesis
Antineoplastic Agents pharmacology
Lipase antagonists & inhibitors
Piperidones chemical synthesis
Piperidones pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 26
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 26873414
- Full Text :
- https://doi.org/10.1016/j.bmcl.2016.01.073