Anti-Cancer Activity and Molecular Docking of Some Pyrano[3,2‑c]quinoline Analogues
Open Access
- 1 January 2020
- journal article
- research article
- Published by Scientific Research Publishing, Inc. in Open Journal of Medicinal Chemistry
- Vol. 10 (01), 1-14
- https://doi.org/10.4236/ojmc.2020.101001
Abstract
Quinoline analogues exhibited diversified biological activities depending on the structure type. A number of natural products with pyrano[3,2-c]quinolone structural motifs and patented chromenes were reported as promising cytotoxic agents. A molecular docking study was employed to investigate the binding and functional properties of 3-amino pyranoquinolinone 2a-c as anti-cancer agents. The three 3-amino pyranoquinolinone 2a-c showed an interesting ability to intercalate the DNA-topoisomerase complex and were able to obtain energetically favorable binding modes (−8.3 - −7.5 kcal/mol). Compound 2c containing butyl chain superiority over the other two compounds 2a-b which appeared to be involved in arene-H interactions with the two dG13 aromatic centers. The butyl chain also appeared to be immersed into a side subpocket formed by the side chains of Asn520 and Glu522 and the backbone amide of Arg503, Gly504, Lys505 and Ile506. Hence, the 3-amino pyranoquinolinone 2c used as starting material to prepare derivatives of pyrano[3,2-c]quinolone containing 1,2,4-triazine ring 4a-b which will enhance the anti-cancer activity. Pyrano[3,2-c]quinoline-2,5-diones 2a-c and 4a-b were evaluated in vitro on cell lines Ehrlich Ascites carcinoma cells (EAC), liver cancer cell line Hep-G2 and breast cancer cell line MCF-7 for the development of novel anticancer agents. The screening results revealed that compounds 4a-b were found most active candidates as anticancer agents.Keywords
This publication has 34 references indexed in Scilit:
- Discovery of 1,2,4-Triazine Derivatives as Adenosine A2A Antagonists using Structure Based Drug DesignJournal of Medicinal Chemistry, 2012
- Discovery of 4-(5-(Cyclopropylcarbamoyl)-2-methylphenylamino)-5-methyl-N-propylpyrrolo[1,2-f][1,2,4]triazine-6-carboxamide (BMS-582949), a Clinical p38α MAP Kinase Inhibitor for the Treatment of Inflammatory DiseasesJournal of Medicinal Chemistry, 2010
- Voreloxin Is an Anticancer Quinolone Derivative that Intercalates DNA and Poisons Topoisomerase IIPLOS ONE, 2010
- Quantitative Proteomics Analysis of Cell Cycle-regulated Golgi Disassembly and ReassemblyOnline Journal of Public Health Informatics, 2010
- New Phenylpropenoids, Bis(1-phenylethyl)phenols, Bisquinolinone Alkaloid, and Anti-inflammatory Constituents from Zanthoxylum integrifoliolumJournal of Natural Products, 2007
- Isolation and Identification of Antifungal and Antialgal Alkaloids fromHaplophyllum sieversiiJournal of Agricultural and Food Chemistry, 2005
- Structures of Cordypyridones A−D, Antimalarial N-Hydroxy- and N-Methoxy-2-pyridones from the Insect Pathogenic Fungus Cordyceps nipponicaThe Journal of Organic Chemistry, 2001
- Topoisomerase-targeting antitumor drugsBiochimica et Biophysica Acta (BBA) - Reviews on Cancer, 1989
- A potent, new, sedative-hypnotic agent: 5,7-dihydro-5,5,7,7-tetramethyl-3-(3-nitrophenyl)furo[3,4-e]-as-triazine 4-oxideJournal of Medicinal Chemistry, 1981
- Aryl-substituted triazines with antidepressant activityJournal of Medicinal Chemistry, 1969