Laboratorio de Síntesis Orgánica, Unidad de Bioquímica, Facultad de Farmacia, Universidad Central de Venezuela, Apartado 47206, Los Chaguaramos, 1041-A Caracas, Venezuela.
Unidad de Estructura Molecular, Fundación Instituto de Estudios Avanzados (IDEA), Apartado 17606, Caracas 1015-A, Venezuela.
Eur J Med Chem. 2015;96:281-95. doi: 10.1016/j.ejmech.2015.04.023. Epub 2015 Apr 10.
A highly regiospecific synthesis of a series of indenoindoles is reported, together with X-ray studies and their activity against human prostate cancer cells PC-3 and LNCaP in vitro. The most effective compound 7,7-dimethyl-5-[(3,4-dichlorophenyl)]-(4bRS,9bRS)-dihydroxy-4b,5,6,7,8,9bhexahydro-indeno[1,2-b]indole-9,10-dione 7q reduced the viability in both cell lines in a time and dose-dependent manner. Inhibitory effects were also observed on the adhesion, migration, and invasion of the prostate cancer cells as well as on clonogenic possibly by inhibition of MMP-9 activity. Molecular docking of 7q and 6k into MMP-9 human active site was also performed to determine the probable binding mode.
报道了一系列茚并吲哚的高区域选择性合成，以及 X 射线研究及其对人前列腺癌细胞 PC-3 和 LNCaP 的体外活性。最有效的化合物 7,7-二甲基-5-[(3,4-二氯苯基)]-(4bRS,9bRS)-二羟基-4b,5,6,7,8,9b 六氢茚并[1,2-b]吲哚-9,10-二酮 7q 以时间和剂量依赖的方式降低了两种细胞系中的活力。还观察到对前列腺癌细胞的粘附、迁移和侵袭的抑制作用，以及对克隆形成的抑制作用，可能是通过抑制 MMP-9 活性。还对 7q 和 6k 进行了分子对接 MMP-9 人活性部位，以确定可能的结合模式。
