Galaka Tamila, Ferrer Casal Mariana, Storey Melissa, Li Catherine, Chao María N, Szajnman Sergio H, Docampo Roberto, Moreno Silvia N J, Rodriguez Juan B
Departamento de Química Orgánica and UMYMFOR (CONICET-FCEyN), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, Ciudad Universitaria, C1428EHA Buenos Aires, Argentina.
Center for Tropical and Emerging Global Diseases and Department of Cellular Biology, University of Georgia, Athens, GA 30602, USA.
Molecules. 2017 Jan 4;22(1):82. doi: 10.3390/molecules22010082.
Based on crystallographic data of the complexes 2-alkyl(amino)ethyl-1,1-bisphosphonates- farnesyl diphosphate synthase, some linear 1,1-bisphosphonic acids and other closely related derivatives were designed, synthesized and biologically evaluated against , the responsible agent of Chagas disease and against , the etiologic agent of toxoplasmosis and also towards the target enzymes farnesyl pyrophosphate synthase of (FPPS) and (FPPS), respectively. The isoprenoid-containing 1,1-bisphosphonates exhibited modest antiparasitic activity, whereas the linear α-fluoro-2-alkyl(amino)ethyl-1,1-bisphosphonates were unexpectedly devoid of antiparasitic activity. In spite of not presenting efficient antiparasitic activity, these data turned out to be very important to establish a structural activity relationship.
基于2-烷基（氨基）乙基-1,1-双膦酸酯-法尼基二磷酸合酶配合物的晶体学数据，设计、合成了一些线性1,1-双膦酸及其密切相关的衍生物，并针对恰加斯病的病原体克氏锥虫以及弓形虫病的病原体刚地弓形虫，分别对其靶标酶布氏锥虫法尼基焦磷酸合酶（TbFPPS）和恶性疟原虫法尼基焦磷酸合酶（PfFPPS）进行了生物学评估。含类异戊二烯的1,1-双膦酸酯表现出适度的抗寄生虫活性，而线性α-氟-2-烷基（氨基）乙基-1,1-双膦酸酯却出人意料地没有抗寄生虫活性。尽管没有表现出有效的抗寄生虫活性，但这些数据对于建立构效关系非常重要。
