Amides derived from heteroaromatic amines and selected steryl hemiesters

Abstract

The current interest of the team has been focused on investigation of novel amides with potential cytotoxicity. The presented series of compounds was synthesized from selected steryl hemiesters and heteroaromatic amines. The synthetic protocol was designed in a simple and economic way, and divided into several general methodologies applicable to the compounds synthesized. The cytotoxicity was tested on cells derived from human T-lymphoblastic leukemia, breast adenocarcinoma and cervical cancer, and compared with tests on normal human fibroblasts. Most of the lanosterol-based compounds (3-5 and 7-10) showed medium to good cytotoxicity, while only two derivatives of cholesterol (18 and 19) showed medium cytotoxicity on human T-lymphoblastic leukemia cell line. The compounds 8 and 9 displayed the reasonable cytotoxicity among this series of amides, tested on the cell lines of T-lymphoblastic leukemia [14.5±0.4 μM (8) and 18.5±3.9 μM (9)], breast adenocarcinoma [19.5±2.1 μM (8) and 23.1±4.0 μM (9)] and cervical cancer [24.8±5.3 μM (8) and 29.1±4.7 μM (9)]. Only the compound 8 was adequately less active on normal human fibroblasts (40.4±11.1 μM).

Keywords: 4-(N,N-dimethylamino)pyridine; 50% solution of propylphosphonic anhydride in ethyl acetate; 9H-fluoren-9-ylmethyl carbonochloridate; Amide; BJ; CEM; Cholesterol; Cytotoxic activity; DCC; DMAP; DMEM; Dulbecco’s modified Eagle’s medium; FBS; FMOC-Cl; HeLa; Heteroaromatic amine; Lanosterol; MCF7; N,N′-dicyclohexylcarbodiimide; T3P; cells of human T-lymphoblastic leukemia; cells of human breast adenocarcinoma; cells of human cervical cancer; foetal bovine serum; normal human fibroblasts.