Diaryl sulfide analogs of combretastatin A-4: toxicogenetic, immunomodulatory and apoptotic evaluations and prospects for use as a new chemotherapeutic drug

Publication date: Available online 2 September 2015 Source:Environmental Toxicology and Pharmacology Author(s): Pamela Castilho de Carvalho, Edson dos Anjos dos Santos, Beatriz Ursinos Catelán Shneider, Renata Matuo, João Renato Pesarini, Andréa Luiza Cunha-Laura, Antônio Carlos Duenhas Monreal, Dênis Pires de Lima, Andréia Conceição Milan Brochado Antoniolli, Rodrigo Juliano Oliveira 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 ag...
Source: Environmental Toxicology and Pharmacology - Category: Environmental Health Source Type: research