Tavares Joana, Ouaissi Ali, Silva Ana Marta, Lin Paul Kong Thoo, Roy Nilanjan, Cordeiro-da-Silva Anabela
IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal.
Parasitol Int. 2012 Jun;61(2):360-3. doi: 10.1016/j.parint.2011.11.005. Epub 2011 Dec 6.
Bisnaphthalimidopropyl (BNIP) derivatives were recently identified as inhibitors of the Leishmania Silent Information Regulator 2 (SIR2) NAD(+)-dependent deacetylase. In this report we have for the first time, determined the potential of these compounds to treat visceral leishmaniasis using BALB/c mice chronically infected with Leishmania infantum as a model. These experiments led to the identification of BNIPdiaminooctane (BNIPDaoct) as an effective compound able to induce significant reduction of the parasite load in the spleen and in the liver. Indeed, at a dose of 1mg/kg, BNIPDaoct was more effective to treat leishmaniasis in a short course treatment (3 or 6 drug administrations) than the standard amphotericin B. Moreover, no indications of hematological toxicity were detected as evaluated by the hemoglobin, hematocrit, white and red blood cell counts, hence making BNIPDaoct a potential therapeutic agent against leishmaniasis.
双萘二甲酰亚胺丙基（BNIP）衍生物最近被鉴定为利什曼原虫沉默信息调节因子2（SIR2）NAD⁺依赖性脱乙酰酶的抑制剂。在本报告中，我们首次以慢性感染婴儿利什曼原虫的BALB/c小鼠为模型，确定了这些化合物治疗内脏利什曼病的潜力。这些实验导致鉴定出双萘二甲酰亚胺二氨基辛烷（BNIPDaoct）是一种有效的化合物，能够显著降低脾脏和肝脏中的寄生虫负荷。事实上，在1mg/kg的剂量下，BNIPDaoct在短疗程治疗（3次或6次给药）中治疗利什曼病比标准两性霉素B更有效。此外，通过血红蛋白、血细胞比容、白细胞和红细胞计数评估，未检测到血液学毒性迹象，因此BNIPDaoct成为抗利什曼病的潜在治疗剂。
