Synthesis and antitumor activities of new N-(5-benzylthiazol-2-yl)-2-(heteryl-5-ylsulfanyl)-acetamides

摘要

Aim. Synthesis of a series of new N-(5-benzyl-thiazol-2-yl)-2-(heteryl-5-ylsulfanyl)-acetamides and study of their anticancer activity. Methods. Organic synthesis, analyticaland spectral methods, pharmacological screening. Results. 2-chloro-N-(5-aryl-1,3-thiazol-2-yl)acetamides 3a-h have been synthesized by the reaction of 2-amino-5-(R-benzyl)thiazoleswith the chloroacetyl chloride. The obtained compounds react with 1-phenyl-1Htetrazole-5- 4, 4-allyl-5-phenyl-4H-1,2,4triazole-3- 5a, 4-allyl-5-furan-2-yl-4H-1,2,4triazole-3- 5b thioles, pyrimidine-2- 6a and 4,6-dimethyl-pyrimidine-2- thioles 6b to forma series of novel N-(5-benzyl-thiazol-2-yl)-2-(heterylsulfanyl)acetamides with yields of65–96. These compounds in the concentration of 10 μM have been evaluated for theiranticancer activity against 60 human cancer cell lines of nine different cancer types: leukemia,melanoma, lung, colon, CNS, ovarian, renal, prostate, and breast cancers. Thesynthesized compounds displayed moderate activity in the in vitro screening with thetested cell lines. However, a selective influence of some compounds on several cancer celllines was observed. The 7c, 8a, 8d and 9c-g compounds have been found to be active andhighly selective towards the HOP-92 Non-Small Cell Lung Cancer cell line (GP = 39.45 –65.63), whereas 2-(4,6-R1-pyrimidin-2-ylsulfanyl)-N-(5-R-benzyl)-thiazol-2-yl-acetamides 9c-h were active towards the UO-31 Renal Cancer cell line (GP = 34.43 –60.58). The 7c possessed significant activity towards the SNB-75 CNS Cancer cell line(GP = –3.83 ), the 7f, towards the OVCAR-4 Ovarian Cancer cell line (GP = 14.66 ),the 8d, towards the HS 578T Breast Cancer cell line (GP = 11.09), the 9g, towards theNCI-H226 Non-Small Cell Lung Cancer (GP = 9.75) and UO-31 Renal Cancer cell lines(GP = 16.35). Conclusions. A series of new 2-amino-5-arylmetylthiazole derivatives wassynthesized. These compounds have anticancer activity.