Faculdade de Medicina Veterinária, Universidade Estadual do Ceará, Fortaleza, CE.
Rev Soc Bras Med Trop. 2011 Oct;44(5):567-71. doi: 10.1590/s0037-86822011000500007.
Visceral leishmaniasis is endemic in 88 countries, with a total of 12 million people infected and 350 million at risk. In the search for new leishmanicidal agents, alkaloids and acetogenins isolated from leaves of Annona squamosa and seeds of Annona muricata were tested against promastigote and amastigote forms of Leishmania chagasi.
Methanol-water (80:20) extracts of A. squamosa leaves and A. muricata seeds were extracted with 10% phosphoric acid and organic solvents to obtain the alkaloid and acetogenin-rich extracts. These extracts were chromatographed on a silica gel column and eluted with a mixture of several solvents in crescent order of polarity. The compounds were identified by spectroscopic analysis. The isolated compounds were tested against Leishmania chagasi, which is responsible for American visceral leishmaniasis, using the MTT test assay. The cytotoxicity assay was evaluated for all isolated compounds, and for this assay, RAW 264.7 cells were used.
O-methylarmepavine, a benzylisoquinolinic alkaloid, and a C37 trihydroxy adjacent bistetrahydrofuran acetogenin were isolated from A. squamosa, while two acetogenins, annonacinone and corossolone, were isolated from A. muricata. Against promastigotes, the alkaloid showed an IC50 of 23.3 µg/mL, and the acetogenins showed an IC50 ranging from 25.9 to 37.6 µg/mL; in the amastigote assay, the IC50 values ranged from 13.5 to 28.7 µg/mL. The cytotoxicity assay showed results ranging from 43.5 to 79.9 µg/mL.
These results characterize A. squamosa and A. muricata as potential sources of leishmanicidal agents. Plants from Annonaceae are rich sources of natural compounds and an important tool in the search for new leishmanicidal therapies.
内脏利什曼病流行于 88 个国家，受感染人数达 1200 万，感染风险人数达 3.5 亿。为寻找新的杀利什曼原虫药物，从番荔枝叶和刺果番荔枝种子中分离得到的生物碱和乙酰基二萜类化合物对恰加斯利什曼原虫的前鞭毛体和无鞭毛体进行了测试。
用 10%磷酸和有机溶剂从番荔枝叶和刺果番荔枝种子的甲醇-水（80:20）提取物中提取富含生物碱和乙酰基二萜类的提取物。这些提取物在硅胶柱上进行色谱分离，并用极性逐渐增加的混合溶剂进行洗脱。通过光谱分析鉴定化合物。用 MTT 试验测定了分离得到的化合物对恰加斯利什曼原虫的活性。用 RAW 264.7 细胞进行细胞毒性试验，评价所有分离化合物的细胞毒性。
从番荔枝中分离得到苄基异喹啉生物碱 O-甲基阿尔泊啡和 C37 三羟基相邻双四氢呋喃乙酰基二萜，从刺果番荔枝中分离得到两种乙酰基二萜 annonacinone 和 corossolone。对前鞭毛体，生物碱的 IC50 为 23.3µg/mL，乙酰基二萜的 IC50 为 25.9-37.6µg/mL；在无鞭毛体试验中，IC50 值为 13.5-28.7µg/mL。细胞毒性试验结果为 43.5-79.9µg/mL。
这些结果表明番荔枝和刺果番荔枝可能是杀利什曼原虫药物的潜在来源。番荔枝科植物是天然化合物的重要来源，也是寻找新的杀利什曼原虫疗法的重要工具。
