Targeting triple-negative breast cancer cells with 6,7-bis(hydroxymethyl)-1H,3H-pyrrolo[1,2-c]thiazoles

• Published in: European journal of medicinal chemistry Vol. 79; pp. 273 - 281
• Main Authors: Santos, Kathleen, Laranjo, Mafalda, Abrantes, Ana Margarida, Brito, Ana F., Gonçalves, Cristina, Sarmento Ribeiro, Ana Bela, Botelho, M. Filomena, Soares, Maria I.L., Oliveira, Andreia S.R., Pinho e Melo, Teresa M.V.D.
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 22-05-2014
• Subjects: 6,7-Bis(hydroxymethyl)-1H,3H-pyrrolo[1,2-c]thiazole; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antitumor activity; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell Cycle - drug effects; Cell Death - drug effects; Cell Proliferation - drug effects; Cell Survival - drug effects; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Female; Humans; MCF-7 Cells; Molecular Structure; Pyrroles - chemical synthesis; Pyrroles - chemistry; Pyrroles - pharmacology; Structure-Activity Relationship; Thiazoles - chemical synthesis; Thiazoles - chemistry; Thiazoles - pharmacology; Triple-negative breast cancer; Tumor Cells, Cultured; 6,7-Bis(hydroxymethyl)-1H,3H-pyrrolo[1,2-c]thiazole; Antitumor activity; Breast cancer; Triple-negative breast cancer
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2014.04.008

Further studies on 6,7-bis(hydroxymethyl)-1H,3H-pyrrolo[1,2-c]thiazoles as anticancer agents against breast cancer are reported, allowing to demonstrate the potential of these compounds for the therapy of the triple-negative breast cancer, the most challenging tumors in clinical practice. These compounds were assayed for their in vitro cytotoxicity on several human breast cancer cell lines (MCF7, HCC1954 and HCC1806 cell lines). Particularly interesting were the results obtained for 4-hydroxyphenyl substituted derivative, which proved to be the most promising compound regarding HCC1806 cell line, a triple-negative breast cancer. The effects of the two most active compounds on cell survival, viability, cell cycle, DNA damage and expression of proteins related to cell death pathways were studied. The reported results consolidate the potential of 6,7-bis(hydroxymethyl)-1H,3H-pyrrolo[1,2-c]thiazoles for the therapy of breast cancer, particularly the triple-negative.
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•Synthesis of a range of 6,7-bis(hydroxymethyl)-1H,3H-pyrrolo[1,2-c]thiazoles (PT).•In vitro cytotoxicity of PTs on human breast cancer cell lines was evaluated.•The effects of two promising compounds on cancer biology was studied.•The reported results indicate that the studied compounds may induce DNA damage.•Introduce the potential of PTs for the therapy of triple-negative breast cancer.