Gutiérrez-Rebolledo Gabriel Alfonso, Drier-Jonas Susan, Jiménez-Arellanes María Adelina
Unidad de Investigación Médica en Farmacología, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, Col. Doctores, Delg. Cuauhtémoc, 06720 Ciudad de México, Mexico.
Unidad de Investigación Médica en Farmacología, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, Col. Doctores, Delg. Cuauhtémoc, 06720 Ciudad de México, Mexico.
Asian Pac J Trop Med. 2017 Dec;10(12):1105-1110. doi: 10.1016/j.apjtm.2017.10.016. Epub 2017 Nov 7.
Leishmaniasis is considered as an emerging, uncontrolled disease and is endemic in 98 countries. Annually, about 2 million cases of cutaneous and 500000 cases of visceral-type leishmaniasis are recorded and 60000 persons died from the disease. In Mexico, cutaneous leishmaniasis is known as chiclero's ulcer and is reported in 22 states, it is considered as a health problem. For its treatment, pentavalent antimonial drugs are administered. These drugs cause severe side effects, are costly. Drug-resistant cases have been reported and have been developing for over 70 years. One alternative to the drugs that are currently available is to find active molecules in medicinal plants. Dihydrocorynantheine, corynantheine and corynantheidine are active against Leishmania major, while harmane, pleiocarpin, buchtienin, luteolin and quercetin are active against Leishmania donovani. In Mexico, about 20 medicinal plants have been evaluated against Leishmania mexicana, among which the most active are Tridax procumbens, Lonchocarpus xuul and Pentalinon andrieuxii. From these plants, active compounds with IC ≤ 30 μg/mL or μM have been isolated, such as 3(S)-16,17-didehydrofalcarinol or Oxylipin, cholestra-4,20,24-trien-3-one or pentalinosterol, 24-methylcholest-4-24(28)-dien-3-one, cholest-4-en-3-one, 6,7-dihydroneridie-none, neridienone, cholest-5,20,24-trien-3β-ol, and isocordoin. Today, only pentalinonsterol has been synthesized and assayed in the visceral leishmaniasis experimental model using BALB/c mice infected with Leishmania donovani. Liposome formulation of this compound administered by intravenous route at 2.5 mg/kg showed a significant reduction of parasite load in mouse liver and spleen.
利什曼病被视为一种新出现的、未得到控制的疾病,在98个国家呈地方性流行。每年记录的皮肤型利什曼病病例约200万例,内脏型利什曼病病例50万例,6万人死于该病。在墨西哥,皮肤型利什曼病被称为“胶树采集者溃疡”,在22个州均有报告,被视为一个健康问题。其治疗采用五价锑剂。这些药物会引起严重的副作用,成本高昂。耐药病例已有报告,且耐药情况已发展了70多年。目前现有药物的一种替代方法是在药用植物中寻找活性分子。二氢可待因碱、可待因碱和可待因定对硕大利什曼原虫有活性,而哈尔满、多果榄仁碱、布氏番荔枝碱、木犀草素和槲皮素对杜氏利什曼原虫有活性。在墨西哥,已对约20种药用植物针对墨西哥利什曼原虫进行了评估,其中活性最强的是平卧银胶菊、徐氏豆薯和安氏五蕊寄生。从这些植物中分离出了IC≤30μg/mL或μM的活性化合物,如3(S)-16,17-二脱氢法卡林醇或氧化脂质、胆甾-4,20,24-三烯-3-酮或五蕊寄生甾醇、24-甲基胆甾-4-24(28)-二烯-3-酮、胆甾-4-烯-3-酮、6,7-二氢奈里地酮、奈里地酮、胆甾-5,20,24-三烯-3β-醇和异紫堇定。如今,只有五蕊寄生甾醇在感染杜氏利什曼原虫的BALB/c小鼠内脏利什曼病实验模型中进行了合成和检测。该化合物的脂质体制剂通过静脉途径以2.5mg/kg给药,显示小鼠肝脏和脾脏中的寄生虫负荷显著降低。