Synthesis and evaluation of anticancer and antiobesity activity of 1-ethoxy carbonyl-3,5-bis (3'-indolyl methylene)-4-pyperidone analogs
| Autor: | K.V.N. Satya Srinivas, Komuraiah Buduma, Kotesh Kumar Jonnala, Pooja Sharma, Paramjit Grover, Niranjana Kumar Arigari, Aparna Shukla, Ashok Kumar Tiwari, Srinivas Chinde, Feroz Khan, Anand Kumar Dommati |
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| Rok vydání: | 2015 |
| Předmět: |
Stereochemistry
Clinical Biochemistry Pharmaceutical Science Antineoplastic Agents 01 natural sciences Biochemistry Medicinal chemistry HeLa Potassium carbonate 03 medical and health sciences chemistry.chemical_compound Structure-Activity Relationship 0302 clinical medicine Cell Line Tumor Drug Discovery Structure–activity relationship Humans Lipase Methylene Enzyme Inhibitors Molecular Biology Piperidones Cell Proliferation chemistry.chemical_classification biology Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Chemistry Organic Chemistry biology.organism_classification 0104 chemical sciences Enzyme Docking (molecular) 030220 oncology & carcinogenesis biology.protein Molecular Medicine Piperidine Anti-Obesity Agents Drug Screening Assays Antitumor |
| Zdroj: | Bioorganicmedicinal chemistry letters. 26(6) |
| ISSN: | 1464-3405 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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