Química Orgánica de Productos Naturales, Instituto de Química, Facultad de Ciencias Exactas y Naturales, Universidad de Antioquia, Calle 70 No. 52-21, Medellín A. A 1226, Colombia.
PECET-Programa de Estudio y Control de Enfermedades Tropicales. Facultad de Medicina, Universidad de Antioquia, Calle 70 No. 52-21, Medellín A. A 1226, Colombia.
Molecules. 2017 Dec 29;23(1):70. doi: 10.3390/molecules23010070.
Cutaneous leishmaniasis (CL) is a neglected tropical disease, which causes severe skin lesions. Due to the lack of effective vaccines, and toxicity or reduced effectiveness of available drugs in addition to complex and prolonged treatments, there is an urgent need to develop alternatives for the treatment for CL with different mechanisms of action. In our effort to search for new promising hits against parasites we prepared 18 acyl hydrazone derivatives of thiochroman-4-ones. Compounds were evaluated for their in vitro antileishmanial activity against the intracellular amastigote form of and cytotoxic activity against human monocytes (U-937 ATCC CRL-1593.2). Our results show that derivatization of the thiochroman-4-ones with acyl hydrazones significantly enhances the antileishmanial activity. Among the compounds tested semicarbazone and thiosemicarbazone derivatives of thioflavanone and displayed the highest antileishmanial activities, with EC values of 5.4 and 5.1 µM and low cytotoxicities (100.2 and 50.1 µM respectively), resulting in higher indexes of selectivity (IS).
皮肤利什曼病（CL）是一种被忽视的热带病，会导致严重的皮肤损伤。由于缺乏有效的疫苗，以及现有药物的毒性或效力降低，再加上复杂和长期的治疗，因此迫切需要开发具有不同作用机制的替代疗法来治疗 CL。在我们努力寻找针对寄生虫的新有前途的药物的过程中，我们制备了 18 种硫代色满-4-酮酰腙衍生物。对化合物进行了体外抗利什曼原虫活性（针对内阿米巴形式）和对人单核细胞（U-937 ATCC CRL-1593.2）的细胞毒性活性的评估。我们的研究结果表明，硫代色满-4-酮的酰腙化显著增强了抗利什曼原虫活性。在所测试的化合物中，硫代黄酮和硫代色满酮的半卡巴腙和硫代卡巴腙衍生物表现出最高的抗利什曼原虫活性，EC 值分别为 5.4 和 5.1 μM，细胞毒性低（分别为 100.2 和 50.1 μM），选择性指数（IS）较高。
