Compostos de coordenação como agentes antitumorais: desafios e perspectivas da química computacional no desenvolvimento de metalofármacos

Abstract

Cancer remains one of the leading causes of death worldwide and continues to pose a major challenge to modern medicine due to its molecular heterogeneity, high adaptive capacity, and frequent development of therapeutic resistance. In this context, coordination complexes have attracted increasing interest as potential anticancer agents because of their unique structural and electronic properties, which enable mechanisms of action distinct from those of conventional organic drugs. At the same time, computational chemistry has become an essential tool for rational drug design by enabling the investigation of molecular properties, prediction of interactions with biological targets, and estimation of thermodynamic parameters relevant to pharmacological activity. This monograph presents a literature review on the application of coordination complexes in cancer treatment, with emphasis on platinum-based compounds and the limitations associated with their toxicity and tumor resistance. In addition, the main computational approaches used to model these systems are discussed, including density functional theory, molecular mechanics, molecular dynamics, and free energy calculations, highlighting the challenges related to the parameterization of transition metals in classical force fields. It is concluded that the integration of coordination chemistry and computational chemistry represents a promising strategy for the rational development of more selective, effective, and less toxic metallodrugs, although significant methodological challenges remain to be addressed.