作者: Liu, Shuwen ; Zhan, Zhikun ; Zhang, Tao ; Liao, Shengrong ; Liang, Zhi ; Fenical, William ; Li, Kunlong ; Tian, Yuanxin ; Liu, Yonghong ; Chen, Yulian ; Luo, Xiaowei ; Fang, Wei ; Tang, Lan ; Zhou, Xuefeng

Anti-renal cell carcinoma (RCC) agents with new mechanisms of action are urgently needed. Twenty-seven natural products of the piericidin class, including 17 new ones, are obtained from a marine-derived Streptomyces strain, and several of them show strong inhibitory activities against ACHN renal carcinoma cells. By exploring the mechanisms of two representative natural piericidin compounds, piericidin A (PA) and glucopiericidin A (GPA), peroxiredoxin 1 (PRDX1) is detected as a potential target by transcriptome data of PA-treated ACHN cells, as well as the paired RCC tumor versus adjacent nontumor tissues. PA and GPA induce cell apoptosis through reducing the reactive oxygen species level caused by upregulated PRDX1 mRNA and protein level subsequently and exhibit potent antitumor efficacy in nude mice bearing ACHN xenografts, with increasing PRDX1 expression in tumor. The interaction between PA/GPA and PRDX1 was supported by the docking analysis and surface plasmon resonance. Moreover, the translocation of PRDX1 into the nucleus forced by PA/GPA is proposed to be a key factor for the anti-RCC procedure. Piericidins provide a novel scaffold for further development of potent anti-RCC agents, and the new action mechanism of these agents targeting PRDX1 may improve upon the limitations of existing targeted drugs for the treatment of renal cancer.

2006-01-01·Journal of the American Chemical Society1区 · 化学

Titanium(II)-Mediated Cyclizations of (Silyloxy)enynes: A Total Synthesis of (−)-7-Demethylpiericidin A₁

1区 · 化学

Article

作者: Keaton, Katie A. ; Phillips, Andrew J.

A concise total synthesis of 7-demethylpiericidin A1 has been completed. The synthesis features a titanium(II)-mediated cyclization of a (silyloxy)enyne as the key step and proceeds in nine steps from tiglic aldehyde.

1996-01-01·The Journal of Antibiotics4区 · 医学

New Piericidin Antibiotics, 7-Demethylpiericidin A1 and 7-Demethyl-3'-rhamnopiericidin A1.

4区 · 医学

Article

作者: Kimura, Ken-ichi ; Miyata, Nobuo ; Yoshihama, Makoto ; Takahashi, Hidetoshi ; Uramoto, Masakazu

The isolation, structures, and biol. properties of 2 new antibiotics of the piericidin family, SN-198-D (I) and SN-198-B (II), are reported.I and II were purified from the fermentation broth of Streptomyces SN-198 and their structures were confirmed to be 7-demethylpiericidin A₁ and 7-demethyl-3'-rhamnopiericidin A₁, resp., by UV, IR, NMR, and mass spectroscopy.I and II exhibited antimicrobial and antitumor activities.Some structure-activity correlations among I, II, piericidin A₁ (SN-198-E), and 3'-rhamnopiericidin A₁ (SN-198-C) were established.

100 项与 SN-198D 相关的药物交易

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