Novel Classes of Antibacterial Drugs in Clinical Development, a Hope in a Post-antibiotic Era.

Bacterial resistance is a growing problem worldwide and is estimated that deaths by infectious diseases associated with resistant pathogens will generate 10 million deaths per year in 2050. This problem becomes more serious due to the low level of research and development of new drugs, which has fallen drastically in the last 40 years. For example, in the last decade of a total of 293 new drugs approved by the FDA, only 9 corresponded to antimicrobial drugs and none constituted a new structural class. The majority of the molecules in the clinical phase II or III, coming from modifications of drugs in clinical use, this strategy makes easier the bacterial susceptibility to generate resistance through the mechanisms expressed for their drug predecessors. Under this scenario, it is urgent to generate the most novel strategies for the development of antibacterial compounds with new targets or mechanism of action, without a structural relationship with the antibiotic drugs predecessors. Under this look, the present review addresses the development of the latest antibacterial drugs in clinical phases II and III, analyzing the design strategies by which these new molecules were obtained and the structure-activity relationship of these new families of antibiotics, in order to define the state of the vanguard antibacterial drugs in the post-antibiotic era.

Gold nanoparticles stabilized with ßcyclodextrin-2-amino-4-(4-chlorophenyl)thiazole complex: A novel system for drug transport.

While 2-amino-4-(4-chlorophenyl)thiazole (AT) drug and thiazole derivatives have several biological applications, these compounds present some drawbacks, such as low aqueous solubility and instability. A new complex of ßCD-AT has been synthesized to increase AT solubility and has been used as a substrate for the deposit of solid-state AuNPs via magnetron sputtering, thus forming the ßCD-AT-AuNPs ternary system, which is stable in solution. Complex formation has been confirmed through powder X-ray diffraction and 1D and 2D nuclear magnetic resonance. Importantly, the amine and sulfide groups of AT remained exposed and can interact with the surfaces of the AuNPs. The complex association constant (970 M-1) has been determined using phase solubility analysis. AuNPs formation (32 nm average diameter) has been studied by UV-Visible spectroscopy, transmission/scanning electron microscopy and energy-dispersive X-ray analysis. The in vitro permeability assays show that effective permeability of AT increased using ßCD. In contrast, the ternary system did not have the capacity to diffuse through the membrane. Nevertheless, the antibacterial assays have demonstrated that AT is transferred from ßCD-AT-AuNPs, being available to exert its antibacterial activity. In conclusion, this novel ßCD-AT-AuNPs ternary system is a promising alternative to improve the delivery of AT drugs in therapy.