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

Abstract

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, analytical and 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)thiazoles with the chloroacetyl chloride. The obtained compounds react with 1-phenyl-1Htetrazole-5-4, 4-allyl-5-phenyl-4H-[1,2,4]triazole-3-5a, 4-allyl-5-furan-2-yl-4H-[1,2,4] triazole-3-5b thioles, pyrimidine-2-6a and 4,6-dimethyl-pyrimidine-2-thioles 6b to form a series of novel N-(5-benzyl-thiazol-2-yl)-2-(heterylsulfanyl)acetamides with yields of 65-96%. These compounds in the concentration of 10 μM have been evaluated for their anticancer activity against 60 human cancer cell lines of nine different cancer types: leukemia, melanoma, lung, colon, CNS, ovarian, renal, prostate, and breast cancers. The synthesized compounds displayed moderate activity in the in vitro screening with the tested cell lines. However, a selective influence of some compounds on several cancer cell lines was observed. The 7c, 8a, 8d and 9c-g compounds have been found to be active and highly 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 the NCI-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 was synthesized. These compounds have anticancer activity.