TZD-Based Hybrid Molecules Act as Dual Anti- and Anti- Agents.

Two distinct intracellular pathogens, namely and cause major public health problems worldwide. In addition, serious and challenging health problems of co-infections of with have been recorded, especially in developing countries. Due to this fact, as well as the frequent cases of resistance to the current drugs, novel anti-infectious therapeutics, especially those with dual (anti- and anti-) modes of action, are needed. To address this issue, we explored the anti- potential of thiazolidinedione-based (TZD-based) hybrid molecules with proven anti- potency. Several TZD hybrids with pyridine-4-carbohydrazone (PCH) or thiosemicarbazone (TSC) structural scaffolds were more effective and more selective than sulfadiazine (SDZ) and trimethoprim (TRI). Furthermore, all of these molecules were more selective than pyrimethamine (PYR). Further studies for the most potent TZD-TSC hybrids , and and TZD-PCH hybrid molecule proved that these compounds are non-cytotoxic, non-genotoxic and non-hemolytic. Moreover, they could cross the blood- (BBB), which is a critical factor linked with ideal anti- drug development. Finally, since a possible link between infection and the risk of glioblastoma has recently been reported, the cytotoxic potential of TZD hybrids against human glioblastoma cells was also evaluated. TZD-PCH hybrid molecule was found to be the most effective, with an IC of 19.36 ± 1.13 µg/mL against T98G cells.