A Novel Compound from the Phenylsulfonylpiperazine Class: Evaluation of In Vitro Activity on Luminal Breast Cancer Cells

• Published in: Molecules (Basel, Switzerland) Vol. 29; no. 18; p. 4471
• Main Authors: da Silva, Fernanda Cardoso, Martinho, Ana Clara Cassiano, Ferreira, Helen Soares Valença, Siqueira, Raoni Pais, Arruda, Vinicius Marques, Guerra, Joyce Ferreira da Costa, de Souza, Maria Laura Dos Reis, Landin, Emanuelly Silva, Rezende Júnior, Celso de Oliveira, de Araújo, Thaise Gonçalves
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 20-09-2024; MDPI
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antioxidants; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer therapies; Cell Line, Tumor; Cell Movement - drug effects; Cell Proliferation - drug effects; Cell Survival - drug effects; Cells; chemotherapy; Cytotoxicity; Development and progression; Disease; Drug Screening Assays, Antitumor; Epithelial-Mesenchymal Transition - drug effects; Ethylenediaminetetraacetic acid; Female; Humans; MCF-7 Cells; Medical prognosis; Metastasis; Nitrogen; NMR; Nuclear magnetic resonance; phenylsulfonylpiperazine; Piperazines - chemistry; Piperazines - pharmacology; Structure-Activity Relationship; sulfonamides; Tumors; Canada; Massachusetts; breast cancer; phenylsulfonylpiperazine; sulfonamides; chemotherapy; cytotoxicity
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules29184471

Breast cancer (BC) is the most common cancer in women, and is characterized by its histological and molecular heterogeneity. Luminal BC is an estrogen receptor-positive subtype, with varied clinical courses. Although BC patients are eligible for hormone therapy, both early and late relapses still occur, and thus there is a demand for new cytotoxic and selective treatment strategies for these patients. In the present study, inspired by the structure of phenylsulfonylpiperazine, a series of 20 derivatives were tested in bioassays against MCF7, MDA-MB-231 and MDA-MB-453 BC cells to discover new hit compounds. After 48 h of treatment, 12 derivatives impaired cell viability and presented significant IC
values against at least one of the tumor lineages. Overall, the luminal BC cell line MCF7 was more sensitive to treatments. Compound
, (4-(1H-tetrazol-1-yl)phenyl)(4-((4-chlorophenyl)sulfonyl)piperazin-1-yl)methanone, was the most promising, with IC
= 4.48 μM and selective index (SI) = 35.6 in MCF7 cells. Compound
also presented significant antimigratory and antiproliferative activities against luminal BC cells, possibly by affecting the expression of genes involved in the epithelial-mesenchymal transition mechanism, upregulating E-Cadherin transcripts (
). Our findings suggest that phenylsulfonylpiperazine derivatives are potential candidates for the development of new therapies, especially those targeting luminal BC.