Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, Diadema, Brazil.
Instituto de Biociências, Universidade Estadual Paulista, São Vicente, Brazil.
Curr Top Med Chem. 2022;22(19):1626-1633. doi: 10.2174/1568026622666220707095718.
The fractionation of the n-hexane phase of the EtOH extract from the leaves of Duguetia lanceolata (Annonaceae) led to the identification of the sesquiterpene (-)-cyclocolorenone.
Chemical characterization, including determination of the absolute stereochemistry, and in vitro evaluation of antileishmanial activity of the sesquiterpene (-)-cyclocolorenone, isolated from D. lanceolata, were carried out.
(-)-Cyclocolorenone was isolated from D. lanceolata leaves using different chromatographic steps and its structure was defined by analysis of NMR and ESI-HRMS data. Additionally, the absolute configuration of (-)-cyclocolorenone was ambiguously assigned by means of vibrational circular dichroism (VCD). Antileishmanial activity of (-)-cyclocolorenone was evaluated on promastigote and amastigote forms of Leishmania (Leishmania) amazonensis. The integrity of the cell membrane of L. (L.) amazonensis was analyzed using the SYTOX green probe.
(-)-(1R,6S,7R,10R)-Cyclocolorenone displayed activity against promastigotes and amastigotes forms of L. (L.) amazonensis with IC of 4.54 and 28.44 µM, respectively. Furthermore, this compound was non-toxic in J774 macrophage cells (CC > 458.71 µM) with a selectivity index > 100 (promastigotes) and > 32.2 (amastigotes). Additionally, (-)-cyclocolorenone was observed to target the parasite cell membrane.
Obtained data suggested that (-)-cyclocolorenone, in which absolute configuration was determined, can be considered as a scaffold for the development of new drugs for the treatment of leishmaniasis.
从杜古埃蒂亚·兰塞奥拉塔（番荔枝科）叶的乙醇提取物的正己烷部分分离出倍半萜烯（-）-环柯罗伦酮。
对从杜古埃蒂亚·兰塞奥拉塔中分离出的倍半萜烯（-）-环柯罗伦酮进行化学表征，包括确定其绝对立体化学结构，并进行体外抗利什曼原虫活性评价。
使用不同的色谱步骤从杜古埃蒂亚·兰塞奥拉塔的叶子中分离出（-）-环柯罗伦酮，并通过 NMR 和 ESI-HRMS 数据分析确定其结构。此外，通过振动圆二色性（VCD）模糊地确定了（-）-环柯罗伦酮的绝对构型。（-）-环柯罗伦酮对利什曼原虫（利什曼原虫）亚马逊变体的前鞭毛体和无鞭毛体形式的抗利什曼原虫活性进行了评估。使用 SYTOX 绿色探针分析了 L.（L.）亚马逊变体细胞膜的完整性。
（-）-（1R，6S，7R，10R）-环柯罗伦酮对 L.（L.）亚马逊变体的前鞭毛体和无鞭毛体形式均具有活性，IC 分别为 4.54 和 28.44 µM。此外，该化合物在 J774 巨噬细胞（CC > 458.71 µM）中无毒性，其选择性指数> 100（前鞭毛体）和> 32.2（无鞭毛体）。此外，（-）-环柯罗伦酮被观察到靶向寄生虫细胞膜。
获得的数据表明，（-）-环柯罗伦酮，其绝对构型已确定，可被视为开发用于治疗利什曼病的新药的支架。
