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Chiral 6-hydroxymethyl-1H,3H-pyrrolo[1,2-c]thiazoles: novel antitumor DNA monoalkylating agents.

Abstract
New chiral 1H,3H-pyrrolo[1,2-c]thiazoles were synthesized and screened for their in vitro activity as anti-cancer agents in three human tumor cell lines, colorectal adenocarcinoma, melanoma and breast adenocarcinoma. (R)-6-Hydroxymethyl-5-methyl-3-phenyl-1H,3H-pyrrolo[1,2-c]thiazole and the corresponding benzylcarbamate showed selectivity for breast cancer cell lines with IC(50) values of 2.4 microM and 2.2 microM, respectively. The latter also showed significant activity against colorectal adenocarcinoma cancer cell lines (IC(50) = 8.7 microM). In contrast, the 7-hydroxymethyl-5-methyl-3-phenyl-1H,3H-pyrrolo[1,2-c]thiazole gave moderate anti-cancer activity. The performance against breast cancer cell lines (IC(50) = 1.0 microM) of a potential bisalkylating agent, a (3R)-6,7-bis(hydroxymethyl)-1H,3H-pyrrolo[1,2-c]thiazole, wasn't significantly different from the one observed for the monoalkylating derivatives indicating that the main mechanism of action may in fact be the monoalkylation process.
AuthorsMaria I L Soares, Ana Filipa Brito, Mafalda Laranjo, Ana Margarida Abrantes, M Filomena Botelho, José A Paixão, Ana Matos Beja, Manuela Ramos Silva, Teresa M V D Pinho E Melo
JournalEuropean journal of medicinal chemistry (Eur J Med Chem) Vol. 45 Issue 10 Pg. 4676-81 (Oct 2010) ISSN: 1768-3254 [Electronic] France
PMID20705366 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2010 Elsevier Masson SAS. All rights reserved.
Chemical References
  • Antineoplastic Agents, Alkylating
  • Pyrroles
  • Thiazoles
  • DNA
Topics
  • Adenocarcinoma (drug therapy)
  • Antineoplastic Agents, Alkylating (chemical synthesis, chemistry, pharmacology)
  • Breast Neoplasms (drug therapy)
  • Cell Line, Tumor
  • Colorectal Neoplasms (drug therapy)
  • DNA (metabolism)
  • Drug Screening Assays, Antitumor
  • Female
  • Humans
  • Melanoma (drug therapy)
  • Pyrroles (chemical synthesis, chemistry, pharmacology)
  • Thiazoles (chemical synthesis, chemistry, pharmacology)

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