Carvalho Pamela Castilho, Santos Edson Anjos, Schneider Beatriz Ursinos Catelán, Matuo Renata, Pesarini João Renato, Cunha-Laura Andréa Luiza, Monreal Antônio Carlos Duenhas, Lima Dênis Pires, Antoniolli Andréia Conceição Milan Brochado, Oliveira Rodrigo Juliano
Center for Stem Cells, Cell Therapy and Genetic Toxicology Studies (Centro de Estudos em Células Tronco, Terapia Celular e Genética Toxicológica - CeTroGen), Maria Aparecida Pedrossian University Hospital (Hospital Universitário Maria Aparecida Pedrossian), EBSERH (Empresa Brasileira de Serviços Hospitalares), Campo Grande, Mato Grosso do Sul, Brazil; Graduate Program in Health and Development in the Midwestern Region, Medical School (Faculdade Medicina - FAMED), UFMS, Campo Grande, Mato Grosso do Sul, Brazil.
Biochemistry Laboratory, Center for Biological and Health Sciences, Federal University of Mato Grosso do Sul (Universidade Federal do Mato Grosso do Sul - UFMS), Campo Grande, Mato Grosso do Sul, Brazil.
Environ Toxicol Pharmacol. 2015 Nov;40(3):715-21. doi: 10.1016/j.etap.2015.08.028. Epub 2015 Sep 2.
Combretastatin A-4 exhibits efficient anti-cancer potential in human tumors, including multidrug-resistant tumors. We evaluated the mutagenic, apoptotic and immunomodulatory potential of two diaryl sulfide analogs of combretastatin A-4, 1,2,3-trimethoxy-5-([4-methoxy-3-nitrophenyl]thio)benzene (analog 1) and 1,2,3-trimethoxy-5-([3-amino-4-methoxyphenyl]thio)benzene (analog 2), as well as their association with the anti-tumor agent cyclophosphamide, in Swiss mice. Such evaluation was achieved using the comet assay, peripheral blood micronucleus test, splenic phagocytosis assay, and apoptosis assay. Both analogs were found to be genotoxic, mutagenic and to induce apoptosis. They also increased splenic phagocytosis, although this increase was more pronounced for analog 2. When combined with cyclophosphamide, analog 1 enhanced the mutagenic and apoptotic effects of this anti-tumor agent. In contrast, analog 2 did not enhance the effects of cyclophosphamide and prevented apoptosis at lower doses. These data suggest that analog 1 could be an adjuvant chemotherapeutic agent and possibly improve the anti-neoplastic effect of cyclophosphamide. Additionally, this compound could be a candidate chemotherapeutic agent and/or an adjuvant for use in combined anti-cancer therapy.
康普瑞他汀A - 4在包括多药耐药肿瘤在内的人类肿瘤中展现出有效的抗癌潜力。我们评估了康普瑞他汀A - 4的两种二芳基硫醚类似物，即1,2,3 - 三甲氧基 - 5 - ([4 - 甲氧基 - 3 - 硝基苯基]硫代)苯（类似物1）和1,2,3 - 三甲氧基 - 5 - ([3 - 氨基 - 4 - 甲氧基苯基]硫代)苯（类似物2）的致突变、凋亡和免疫调节潜力，以及它们与抗肿瘤药物环磷酰胺在瑞士小鼠体内的联合作用。这种评估通过彗星试验、外周血微核试验、脾吞噬试验和凋亡试验来完成。发现这两种类似物均具有遗传毒性、致突变性并能诱导凋亡。它们还增强了脾吞噬作用，不过类似物2的这种增强更为明显。当与环磷酰胺联合使用时，类似物1增强了这种抗肿瘤药物的致突变和凋亡作用。相比之下，类似物2并未增强环磷酰胺的作用，且在较低剂量时可防止凋亡。这些数据表明，类似物1可能是一种辅助化疗药物，并可能提高环磷酰胺的抗肿瘤效果。此外，该化合物可能是一种候选化疗药物和/或用于联合抗癌治疗的辅助药物。
