Chiral 6,7-bis(hydroxymethyl)-1H,3H-pyrrolo[1,2-c]thiazoles with anti-breast cancer properties.

Abstract

The synthesis and biological evaluation of 6,7-bis(hydroxymethyl)-1H,3H-pyrrolo[1,2-c]thiazoles as anticancer agents against MCF7 breast cancer cell lines is reported. The design of the new compounds has been guided considering (3R)-6,7-bis(hydroxymethyl)-5-methyl-3-phenyl-1H,3H-pyrrolo[1,2-c]thiazole as the lead compound due to its good performance against MCF7 breast cancer cell lines (IC(50) = 1.0 μM). The structural changes included the removal of the phenyl group at C-3, the replacement of this group by a 3,4,5-trimethoxyphenyl group, the removal of the methyl group at C-5 from the lead scaffold and the replacement of this group by a phenyl substituent. Overall, these studies showed that the combined presence of a phenyl group at C-3 and a methyl group at C-5 in the 1H,3H-pyrrolo[1,2-c]thiazole ring system is essential to ensure high cytotoxicty against MCF7 breast cancer cell lines. To probe whether the absolute configuration of the lead compound might affect the anticancer activity, its enantiomer was prepared and the activity against MCF7 cells was evaluated. (3S)-6,7-Bis(hydroxymethyl)-5-methyl-3-phenyl-1H,3H-pyrrolo[1,2-c]thiazole proved to be the most active compound so far studied, with IC(50) value of 0.5 μM.

• Authors: Maria I L Soares, Ana Filipa Brito, Mafalda Laranjo, José A Paixão, M Filomena Botelho, Teresa M V D Pinho e Melo
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 60 Pg. 254-62 (Feb 2013) ISSN: 1768-3254 [Electronic] France
• PMID: 23313634 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Chemical References

• 6,7-bis(hydroxymethyl)-5-methyl-3-phenyl-1H,3H-pyrrolo(1,2-c)thiazole
• Antineoplastic Agents
• Pyrroles
• Thiazoles

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Breast Neoplasms (drug therapy, pathology)
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Female
• Humans
• MCF-7 Cells
• Models, Molecular
• Molecular Structure
• Pyrroles (chemical synthesis, chemistry, pharmacology)
• Structure-Activity Relationship
• Thiazoles (chemical synthesis, chemistry, pharmacology)