Dos Santos Edson Dos A, Prado Paulo C, de Carvalho Wanderley R, de Lima Ricardo V, Beatriz E Adilson, de Lima Dênis P, Hamel Ernest, Dyba Marzena A, Albuquerque Sergio
Departamento de Química, Universidade Federal de Mato Grosso do Sul, Av. Senador Filinto Müller, 1555, 79074-460 Campo Grande - MS, Brasil.
Quim Nova. 2013 Feb 1;36(2):279-283. doi: 10.1590/S0100-40422013000200014.
We extended our previous exploration of sulfur bridges as bioisosteric replacements for atoms forming the bridge between the aromatic rings of combretastatin A-4. Employing coupling reactions between 5-iodo-1,2,3-trimethoxybenzene and substituted thiols, followed by oxidation to sulfones with -CPBA, different locations for attaching the sulfur atom to ring A through the synthesis of nine compounds were examined. Antitubulin activity was performed with electrophoretically homogenous bovine brain tubulin, and activity occurred with the 1,2,3-trimethoxy-4-[(4-methoxyphenyl)thio]benzene (), while the other compounds were inactive. The compounds were also tested for leishmanicidal activity using promastigote forms of Leishmania braziliensis (MHOM/BR175/M2904), and the greatest activity was observed with 1,2,3-trimethoxy-4-(phenylthio)benzene () and 1,2,3-trimethoxy-4-[(4-methoxyphenyl) sulfinyl]benzene ().
我们扩展了之前对硫桥作为生物电子等排体替代物的探索，这些替代物用于替代形成康普瑞他汀A - 4芳香环之间桥连的原子。利用5 - 碘 - 1,2,3 - 三甲氧基苯与取代硫醇之间的偶联反应，随后用间氯过氧苯甲酸氧化成砜，通过合成九种化合物研究了硫原子连接到A环的不同位置。用经电泳均一的牛脑微管蛋白进行抗微管蛋白活性测试，1,2,3 - 三甲氧基 - 4 - [(4 - 甲氧基苯基)硫基]苯（）有活性，而其他化合物无活性。还使用巴西利什曼原虫（MHOM/BR175/M2904）的前鞭毛体形式测试了这些化合物的杀利什曼原虫活性，1,2,3 - 三甲氧基 - 4 - （苯硫基）苯（）和1,2,3 - 三甲氧基 - 4 - [(4 - 甲氧基苯基)亚磺酰基]苯（）表现出最大活性。
