Novos compostos da classe dos benzotiazóis: atividades biológicas e alterações moleculares em células tumorais mamárias triplo-negativas

Abstract

Breast cancer is the most commonly diagnosed malignant tumor among women worldwide. Different therapeutic strategies are employed, and for its most aggressive subtype, triple-negative breast cancer (TNBC), chemotherapy remains the main clinical approach. However, the toxicity of the drugs used, the activation of resistance mechanisms, and recurrence rates remain major concerns. In this context, the search for new compounds is urgent, and benzothiazole-derived compounds have stood out due to their ability to modulate the redox and inflammatory status of cells. The present study aimed to evaluate the effects of nine novel compounds from this class in BC cell lines through cytotoxicity, clonogenicity, migration, and qPCR assays. Human non-tumoral cell lines HFF-1 (fibroblast) and MCF 10A (breast), as well as the tumor cell lines MCF7 (luminal BC) and MDA-MB-231 (triple-negative BC), were cultured. Among the tested compounds, only compound 2 showed activity and selectivity, with an IC50 = 12.26 µM and a selectivity index (SI) > 2.0. In addition, it significantly inhibited the clonogenicity and migration of triple-negative cells after 48 hours of treatment with 3.07 µM (IC50/4) and 6.13 µM (IC50/2) of 2. Finally, qPCR assays demonstrated that the compound 2 modulates the transcripts of IL6, TGFβ, KRT18, and VIM. Therefore, we suggest that compound 2 modulates the epithelial–mesenchymal transition process in TNBC cells, thereby controlling their aggressiveness. Additional studies are required to validate other EMT-related targets, including animal models.