Avaliação in silico e in vitro da toxicidade de 2'-hidroxichalconas sintéticas

Abstract

Chalcones constitute a group of bioactive molecules with promising therapeutic potential. Their simple and versatile structure is associated with diverse biological activities, including antimicrobial, antiparasitic, anti-inflammatory, antioxidant, and antitumor effects. These properties are partly linked to their α,³-unsaturated system, which interacts with cellular targets. However, this same structural feature underscores the importance of evaluating their toxicological potential. In this context, this study aimed to assess the in silico and in vitro toxicity of a series of synthetic 2’-hydroxychalcones, seeking to associate structural modifications with their toxicity profiles of these substances. In silico predictions of organspecific toxicity endpoints, adverse outcomes, and interactions with cytochrome P450 enzymes were performed using the ProTox 3.0 server. Additionally, cell viability assays were conducted on LLC-MK2, HK2, RAW 264.7, astrocytes, BV2, PC12, L929, and IEC-6 cell lines using the MTT assay, at concentrations ranging from 3.9 to 250 µM. The in silico predictions indicated a low risk of cardiotoxicity and cytotoxicity but suggested potential immunotoxicity for some compounds and possible inhibition of specific cytochrome P450 enzymes (CYP1A2, CYP2C19, CYP2C9, CYP3A4 and CYPE2E1). The in vitro results showed that chalcones 1A, 1C, and 1D exhibited higher toxicity, causing significant reduction in cell viability in HK-2, RAW 264.7, astrocytes, BV-2, PC-12, L929 and IEC-6 cell lines at concentrations between 31.2 and 62.5 µM. In contrast, chalcones 2C and 3A showed lower cytotoxic effects, with CC50 values exceeding 250 µM. These findings advance the understanding of the structure-toxicity relationship of 2’-hydroxychalcones, contributing to future studies on their therapeutic potential and application in the development of novel pharmacological prototypes.