Antiproliferative activity of O4-benzo[c]phenanthridine alkaloids against HCT-116 and HL-60 tumor cells. Issue 14 (15th July 2015)

• Record Type: Journal Article
• Authors: Hatae, Noriyuki; Fujita, Erina; Shigenobu, Saori; Shimoyama, Sayumi; Ishihara, Yuhsuke; Kurata, Yuhki; Choshi, Tominari; Nishiyama, Takashi; Okada, Chiaki; Hibino, Satoshi
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 25:Issue 14(2015)
• Page Start: 2749
• Page End: 2752
• Publication Date: 2015-07-15
• Subjects: IC50 half maximal inhibitory concentration -- MTT thiazolyl blue tetrazolium bromide -- WST-1 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2, 4-disulfophenyl)-2H-tetrazolium monosodium salt -- 1-methoxy PMS 1-methoxy-5-methylphenazinium methylsulfate -- DFT density functional theory; Benzo[c]phenanthridine alkaloid -- Antiproliferative activity -- DFT calculation -- Antitumor -- Iminium ion; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.05.031
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: The O 4 -benzo[ c ]phenanthridine alkaloids exhibit potent antiproliferative activity against cancer cells, which is derived from their ability to inhibit of topoisomerase I and II. It has been reported that in the alkaloids a cationic quaternary ammonium atom, which results in resonance effects between ring A and B, is necessary for increased antiproliferative activity. These findings indicate the role of their substituents at ring A on inhibition of tumor cell proliferation. In the present study, we systematically assessed the cytotoxic activities of naturally occurring alkaloids and their derivatives containing various ring A substituents against two tumor cell lines, HCT-116 colon tumor cells and HL-60 promyelocytic leukemia cells. Among the cationic iminium alkaloids, which displayed more potent activity than the corresponding neutral derivatives, and the 7, 8-oxygenated benzo[ c ]phenanthridine alkaloids, chelerythrine and NK109, exhibited stronger antiproliferative activity than the 8, 9- and 9, 10-oxygenated alkaloids. The activity of cationic iminium alkaloids could be correlated with the bond lengths of their ring A substituents and the electrostatic potentials of their ammonium molecules by DFT calculation.