Synthesis and screening for anticancer activity of two novel telluro-amino acids: 1,3-Tellurazolidine-4-carboxylic acid and tellurohomocystine

Abstract

Tellurium (Te) containing amino acids and their derivatives have the potential to participate in biological processes, which are currently being studied extensively to understand the function of Te in biological and pharmacological activities. Here, we are reporting the synthesis of two novel Te-containing unnatural amino acids; 1,3-Tellurazolidine-4-carboxylic acid [Te{CH₂CH(COOH)NHCH₂}] 5, and 4,4′-(1,2-Ditellurdiyl)bis(2-aminobutanoic acid), i.e., tellurohomocystine [TeCH₂CH₂CH(NH₂)COOH]₂ 7, synthesized from tellurocystine, and l-methionine as precursors, respectively. These telluro-amino acids were thoroughly characterized by multinuclear (¹H, ¹³C, ¹²⁵Te) NMR spectroscopy, high-resolution ESI–mass spectrometry (ESI–MS), and elemental analysis. The telluro-amino acids 5 and 7 demonstrated good biocompatibility when in vitro cytotoxicity was analyzed on two fibroblast cell lines L929 and NIH/3T3. The treatment of telluro-amino acids 1,3-Tellurazolidine-4-carboxylic acid 5 and tellurohomocystine 7 on breast cancer cell line MCF-7 showed anticancer activity with IC50 values of 7.29 ± 0.27 µg/mL and 25.36 ± 0.12 µg/mL, respectively. The cell cycle distribution studies also revealed arrest at the sub-G1 phase suggesting telluro-amino acids to be apoptotic.