Synthesis and toxicity of monothiooxalamides against human red blood cells, brine shrimp (), and fruit fly ( ).

A new family of monothiooxalamides derived from 2-aminobenzimidazole was synthesized, and their structures were confirmed by H and C one-dimensional and 2D NMR experiments (COSY, HSQC, and HMBC). The antioxidant capacity was evaluated by free radical scavenging assays: 1,1-diphenyl-2-picrylhydrazyl (DPPH•), 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS•), ferric reducing antioxidant power (FRAP), oxygen radical absorbance capacity (ORAC), and the Fe(II) chelating ability. Our work group has previously reported the synthesis and antioxidant activity of monothiooxalamides derived from 2-aminopyridine (). In this study, the hemolytic activity of compounds from the 2-aminopyridine () and 2-aminobenzimidazole () families was evaluated against human red blood cells (RBCs). The concentration at which monothiooxalamides showed no hemolytic activity was chosen to assess their ability to inhibit free radical-induced membrane damage in human RBCs, acute toxicity in brine shrimp, and toxicity against . Compounds with morpholine fragments (, , , and ) showed time- and concentration-dependent protective effects against radical-induced oxidative hemolysis. Moreover, they had the lowest acute toxicity in the brine shrimp lethality assay and a significant increase in chelating activity compared with the other molecules. In particular, monothiooxalamide showed lower toxicity and can be considered for further biological screening and application trials.