PDF(Pubmed)
Abstract：
Xanthoquinodins make up a distinctive class of xanthone-anthraquinone heterodimers reported as secondary metabolites from several fungal species. Through a collaborative multi-institutional screening program, a fungal extract prepared from a Trichocladium sp. was identified that exhibited strong inhibitory effects against several human pathogens (Mycoplasma genitalium, Plasmodium falciparum, Cryptosporidium parvum, and Trichomonas vaginalis). This report focuses on one of the unique samples that exhibited a desirable combination of biological effects: namely, it inhibited all four test pathogens and demonstrated low levels of toxicity toward HepG2 (human liver) cells. Fractionation and purification of the bioactive components and their congeners led to the identification of six new compounds [xanthoquinodins NPDG A1-A5 (1-5) and B1 (6)] as well as several previously reported natural products (7-14). The chemical structures of 1-14 were determined based on interpretation of their 1D and 2D NMR, HRESIMS, and electronic circular dichroism (ECD) data. Biological testing of the purified metabolites revealed that they possessed widely varying levels of inhibitory activity against a panel of human pathogens. Xanthoquinodins A1 (7) and A2 (8) exhibited the most promising broad-spectrum inhibitory effects against M. genitalium (EC50 values: 0.13 and 0.12 μM, respectively), C. parvum (EC50 values: 5.2 and 3.5 μM, respectively), T. vaginalis (EC50 values: 3.9 and 6.8 μM, respectively), and P. falciparum (EC50 values: 0.29 and 0.50 μM, respectively) with no cytotoxicity detected at the highest concentration tested (HepG2 EC50 > 25 μM).
摘要：
黄原醌构成了一类独特的黄原酮-蒽醌异二聚体，据报道是来自几种真菌物种的次级代谢产物。通过合作的多机构筛查计划，从Trichocladiumsp.制备的真菌提取物。被鉴定出对几种人类病原体(生殖支原体，恶性疟原虫,微小隐孢子虫,和阴道毛滴虫）。本报告侧重于表现出理想的生物学效应组合的独特样品之一：即，它抑制了所有四种测试病原体，并对HepG2（人类肝脏）细胞表现出低水平的毒性。生物活性成分及其同源物的分级分离和纯化导致鉴定了六种新化合物[xanthoquinodinsNPDGA1-A5（1-5）和B1（6）]以及几种先前报道的天然产物（7-14）。1-14的化学结构是根据其1D和2DNMR的解释确定的，HRESIMS,和电子圆二色性(ECD)数据。纯化的代谢物的生物学测试表明，它们对一组人类病原体具有广泛不同的抑制活性。XanthoquinodinsA1（7）和A2（8）对生殖支原体表现出最有希望的广谱抑制作用（EC50值：0.13和0.12μM，分别)，C.parvum（EC50值：5.2和3.5μM，分别)，阴道毛虫（EC50值：3.9和6.8μM，分别)，和恶性疟原虫(EC50值：0.29和0.50μM，分别），在最高测试浓度（HepG2EC50>25μM）下均未检测到细胞毒性。
