Synthesis of Nitroaromatic Compounds as Potential Anticancer Agents

Abstract

Twenty-seven nitrated and non-nitrated compounds have been synthesized and tested for their growth inhibitory activity on three human cancer cells lines. Fourteen compounds were able to inhibit more than 50% of the growth of at least one of the cancer cell lines and five compounds exhibited high antiproliferative activity on human cancer cell lines (IC50 < 8.5 μM). The cytotoxicity of the compounds on Vero cell line was established in vitro to evaluate the selectivity. All active compounds have a good leaving group (bromide or chloride) at the benzylic position, indicating that the mechanism of action of these compounds is related to their alkylating properties. Two compounds (3 and 24) were selected for further studies in mice with Ehrlich solid tumors and display significant antitumor effects in vivo.

Ortho-nitrobenzyl derivatives as potential anti-schistosomal agents

“…Compounds 1-15 were synthesized according to previously reported procedures (Lopes et al, 2015) based on variations at the R 1 , R 2 and R 3 positions of sulfateoxamniquine ( Figure 5). We tested the effect of different substituents at the benzylic (-R 3 ) position because it is expected that the mechanism of action is by DNA alkylation.…”

“…The synthesis and characterization of the compounds 1-15 were previously described by us (Lopes et al, 2015). The compounds were synthesized in 1 to 3 steps from commercially available starting materials (p-toluic acid, 4-(bromomethyl)benzoic acid or 4-(chloromethyl)benzoic acid) ( Figure 5).…”

“…This product dissociates forming an electrophilic agent, which alkylates the parasite DNA (Abdul-Ghani et al, 2009) (Figure 2). Nitro-aromatic compounds, such as fexinidazole, benznidazole, and niclosamide, (Figure 3) are known for their pharmacological potential and our group has investigated the biological activities of a series of orthonitrobenzyl derivatives that act as alkylating agents (Lopes et al, 2015;Lopes et al, 2011;Soares et al, 2010).…”

“…This product dissociates forming an electrophilic agent, which alkylates the parasite DNA (Abdul-Ghani et al, 2009) (Figure 2). Nitro-aromatic compounds, such as fexinidazole, benznidazole, and niclosamide, (Figure 3) are known for their pharmacological potential and our group has investigated the biological activities of a series of orthonitrobenzyl derivatives that act as alkylating agents (Lopes et al, 2015;Lopes et al, 2011;Soares et al, 2010).Based on the need for new anti-schistosomal agents, we evaluated the schistosomicidal activity of nitro-aromatic compounds, analogs of "activated" oxamniquine, against S. mansoni in vitro. These compounds would be active per se, without the requirement for sulfotransferase activation, as proposed in Figure 4.…”

Synthesis and evaluation of platinum complexes with potential antitumor activity

“…Reactions were monitored by TLC using silica gel coated plates and different solvent solutions as the mobile phase. The diazide derivatives 7 (Lopes et al, 2015) and 8 (Bitha et al, 1989) were synthesized according to the published procedure.…”