Department of Chemistry, University of Coimbra, Rua Larga, 3004-535 Coimbra, Portugal.
Eur J Med Chem. 2010 Oct;45(10):4676-81. doi: 10.1016/j.ejmech.2010.07.029. Epub 2010 Jul 23.
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.
新的手性 1H,3H-吡咯并[1,2-c]噻唑被合成并筛选其作为三种人类肿瘤细胞系（结肠直肠腺癌、黑色素瘤和乳腺腺癌）的抗癌剂的体外活性。（R）-6-羟甲基-5-甲基-3-苯基-1H,3H-吡咯并[1,2-c]噻唑和相应的苯甲酰胺对乳腺癌细胞系表现出选择性，IC50 值分别为 2.4 μM 和 2.2 μM。后者对结肠直肠腺癌癌细胞系也表现出显著的活性（IC50 = 8.7 μM）。相比之下，7-羟甲基-5-甲基-3-苯基-1H,3H-吡咯并[1,2-c]噻唑表现出中等的抗癌活性。一种潜在的双烷基化剂，（3R）-6,7-双（羟甲基）-1H,3H-吡咯并[1,2-c]噻唑对乳腺癌细胞系的作用（IC50 = 1.0 μM）与单烷基化衍生物观察到的作用没有显著差异，表明主要的作用机制实际上可能是单烷基化过程。
