Chamni Supakarn, Sirimangkalakitti Natchanun, Chanvorachote Pithi, Saito Naoki, Suwanborirux Khanit
Graduate School of Pharmaceutical Sciences, Meiji Pharmaceutical University , 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan.
J Nat Prod. 2017 May 26;80(5):1541-1547. doi: 10.1021/acs.jnatprod.7b00068. Epub 2017 May 1.
A series of hydroquinone 5-O-monoester analogues of renieramycin M were semisynthesized via bishydroquinonerenieramycin M (5) prepared from renieramycin M (1), a major cytotoxic bistetrahydroisoquinolinequinone alkaloid isolated from the Thai blue sponge Xestospongia sp. All 20 hydroquinone 5-O-monoester analogues possessed cytotoxicity with IC values in nanomolar concentrations against the H292 and H460 human non-small-cell lung cancer (NSCLC) cell lines. The improved cytotoxicity toward the NSCLC cell lines was observed from the 5-O-monoester analogues such as 5-O-acetyl ester 6a and 5-O-propanoyl ester 7e, which exhibited 8- and 10-fold increased cytotoxicity toward the H292 NSCLC cell line (IC 3.0 and 2.3 nM, respectively), relative to 1 (IC 24 nM). Thus, the hydroquinone 5-O-monoester analogues are a new generation of the renieramycins to be further developed as potential marine-derived drug candidates for lung cancer treatment.
通过从泰国蓝海绵Xestospongia sp.中分离得到的主要细胞毒性双四氢异喹啉醌生物碱雷尼霉素M（1）制备的双氢醌雷尼霉素M（5），半合成了一系列雷尼霉素M的对苯二酚5-O-单酯类似物。所有20种对苯二酚5-O-单酯类似物均具有细胞毒性，对H292和H460人非小细胞肺癌（NSCLC）细胞系的IC值处于纳摩尔浓度。从5-O-单酯类似物如5-O-乙酰酯6a和5-O-丙酰酯7e中观察到对NSCLC细胞系的细胞毒性有所提高，相对于1（IC 24 nM），它们对H292 NSCLC细胞系的细胞毒性分别增加了8倍和10倍（IC分别为3.0和2.3 nM）。因此，对苯二酚5-O-单酯类似物是新一代的雷尼霉素，有望进一步开发成为潜在的海洋来源肺癌治疗候选药物。
