Department of Applied Biological Science, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Sakyo-ku, Kyoto 606-8522, Japan.
Bioorg Med Chem Lett. 2019 Jun 1;29(11):1390-1394. doi: 10.1016/j.bmcl.2019.03.034. Epub 2019 Mar 26.
The antibacterial and cytotoxic activity of seven racemic lactams and both enantiomers of flavipucine were evaluated. Of the compounds tested in this study, flavipucine and phenylflavipucine displayed bactericidal activity against Bacillus subtilis. These results indicate that the pyridione epoxide moiety is a pharmacophore for antibacterial activity against B. subtilis. Flavipucine showed cytotoxic activity against several cancer cells. The cytotoxic activity of flavipucine against human leukemia HL-60 cells is as strong as that of SN-38, the active metabolite of irinotecan. In contrast, the cytotoxic activity of flavipucine against nonneoplastic HEK293 cells and human normal MRC-5 cells is weaker than that of SN-38. No significant differences in the biological activity of the racemates or enantiomers of flavipucine were observed.
本研究评价了七种外消旋内酰胺和非对映异构体的 flavipucine 的抗菌和细胞毒性活性。在本研究中测试的化合物中，flavipucine 和苯基 flavipucine 对枯草芽孢杆菌具有杀菌活性。这些结果表明，吡啶酮环氧化物部分是对抗枯草芽孢杆菌的抗菌活性的药效团。flavipucine 对几种癌细胞具有细胞毒性活性。flavipucine 对人白血病 HL-60 细胞的细胞毒性活性与伊立替康的活性代谢物 SN-38 相当。相比之下，flavipucine 对非肿瘤性 HEK293 细胞和人正常 MRC-5 细胞的细胞毒性活性弱于 SN-38。flavipucine 的外消旋体或对映异构体的生物学活性没有明显差异。
