Metodologias verdes para a síntese de híbridos estruturais com atividade leishmanicida: uma revisão da literatura

Abstract

Currently, there are resources to control or mitigate the different types of leishmaniasis, however, the disease remains neglected, affecting approximately 700,000 people per year, with higher incidence in tropical and subtropical regions of low- and middle-income countries. As an aggravating factor, conventional therapies are limited, based on drugs such as amphotericin B, miltefosine, and pentavalent antimonials, which present high toxicity, adverse side effects, and issues related to drug resistance. In this context, Medicinal Chemistry has emerged with strategies for the rational design and discovery of new chemotherapeutics, among which structural hybridization stands out, enabling the enhancement of biologically relevant activities by covalently combining two or more pharmacophoric subunits in a single structure. However, several synthetic processes in Medicinal Chemistry still rely on traditional methodologies, and therefore Green Chemistry and its 12 principles play a central role in changing this scenario, promoting safer, more efficient, and sustainable syntheses while minimizing energy consumption, reagent use, and hazardous waste generation. In this sense, this work aimed to perform a systematic literature review on alternative methodologies applied to the development of leishmanicidal hybrids from 2010 to 2025. The research was conducted through the SciFinder database and, by applying predefined inclusion and exclusion criteria, 11 articles were collected on the investigated topic. Regarding alternative methodologies, microwaveassisted synthesis was the most recurrent, highlighting approaches such as one-pot reactions, solvent-free procedures, ultrasound irradiation, and catalysis. From a pharmacological perspective, the hybrids demonstrated superior performance to the parental subunits and comparable efficacy to reference drugs, indicating that the integration of structural hybridization with Green Chemistry principles represents a valid strategy for discovering potential therapeutic agents. Moreover, this review is expected to provide a comprehensive overview of the state of the art and serve as a reference to guide future research in this field.