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.
Highlights
Over the past few years, several quinoline containing compounds are reportable as potential antitumor agents
The results revealed that compounds 2c with butyl group at N-1 position of the quinolone core with IC50 = 10.7 μM at 72 hr was found to be more potent than the reference drug (5-flurouracil) (IC50 = 11.2 μM), On the other hand, compounds 4a-b with triazine moiety exhibited strong activity against HepG2 cell line with IC50: 8.3 and 6.7 μM at 72 hr respectively, which was found to be more potent than the reference drug 5-flurouracil (IC50 = 11.2 μM)
A series of the pyrano[3,2-c]quinolonine analogues were evaluated for its anticancer activity
Summary
Over the past few years, several quinoline containing compounds are reportable as potential antitumor agents. The anti-cancer potential of many of these derivatives has been demonstrated on various cancer cell lines. The strength of quinoline motif in anticancer drug development is evident from clinically used anticancer drugs like Camptothecin, Topotecan and Irinotecan, etc. Pyrano[3,2-c]quinolone is a core structural motif present in many alkaloids possessing important therapeutic activities [9]. Huajiaosimuline (A, Figure 1), a potent and selective anticancer agent towards breast cancer, and zanthosimuline (B, Figure 1), an anticancer agent having activity against multidrug resistant KB-VI cancer cells, were both isolated from Zanthoxylum simulans [10]
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