Rodrigues Felipe A R, Oliveira Augusto C A, Cavalcanti Bruno C, Pessoa Claudia, Pinheiro Alessandra C, de Souza Marcus V N
Laboratório de Oncologia Experimental, Universidade Federal do Ceará, Fortaleza, CE, Brazil.
FioCruz-Fundação Oswaldo Cruz, Instituto de Tecnologia em Fármacos-Far-Manguinhos, Rua Sizenando Nabuco, 100, Manguinhos, 21041-250 Rio de Janeiro, RJ, Brazil.
Sci Pharm. 2013 Sep 22;82(1):21-8. doi: 10.3797/scipharm.1307-25. Print 2014 Jan-Mar.
A series of thirty-two isoniazid derivatives have been evaluated for their activity against four human cancer cell lines with potent cytotoxicity (IC50 ranging from 0.61 to 3.36 μg/mL). The structure-activity relationship (SAR) analysis indicated the number, the positions, and the types of substituents attached to the aromatic ring as being critical factors for the biological activity. Briefly, we observed that the presence of a hydroxyl group on the benzene ring plays an important role in the anticancer activity of this series, especially when it is located in ortho-position. Among the thirty-two compounds, three displayed good cytotoxic activity when compared to the reference drug doxorubicin and are thus being considered leading compounds of this new class.
对32种异烟肼衍生物针对四种具有强细胞毒性的人类癌细胞系（IC50范围为0.61至3.36μg/mL）的活性进行了评估。构效关系（SAR）分析表明，连接在芳环上的取代基的数量、位置和类型是生物活性的关键因素。简而言之，我们观察到苯环上羟基的存在对该系列化合物的抗癌活性起着重要作用，尤其是当它位于邻位时。在这32种化合物中，与参考药物阿霉素相比，有三种显示出良好的细胞毒性活性，因此被认为是这一新类别的先导化合物。
