Evaluation of toxicity on epithelial and tumor cells of biaryl dipeptide tyrosines

• Published in: European journal of medicinal chemistry Vol. 114; pp. 1 - 7
• Main Authors: Vasconcelos, Stanley N.S., Drewes, Carine C., de Vinci Kanda Kupa, Leonard, Farsky, Sandra H.P., Stefani, Hélio A.
• Format: Journal Article
• Language: English
• Published: ISSY-LES-MOULINEAUX Elsevier Masson SAS 23.05.2016; Elsevier
• Subjects: Alkyne; Cell Death - drug effects; Cell Proliferation - drug effects; Cells, Cultured; Chemistry, Medicinal; Dipeptide; Dipeptides - chemical synthesis; Dipeptides - chemistry; Dipeptides - toxicity; Dose-Response Relationship, Drug; Human Umbilical Vein Endothelial Cells - cytology; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Life Sciences & Biomedicine; Melanoma; Molecular Structure; Neoplasms - metabolism; Neoplasms - pathology; Pharmacology & Pharmacy; Science & Technology; Structure-Activity Relationship; Tumor; Tyrosine; Tyrosine - chemical synthesis; Tyrosine - chemistry; Tyrosine - toxicity; Tyrosine; Dipeptide; Tumor; Melanoma; Alkyne; DYNAMIC O-(2-F-18-FLUOROETHYL)-L-TYROSINE PET
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2016.02.062

We report a method to obtain biaryl dipeptide tyrosine via Suzuki–Miyaura and alkynyl dipeptide tyrosine by Sonogashira cross-coupling reactions. Analysis of the biological action of biaryl dipeptide tyrosine 4d compound showed its ability to impair the metabolism and proliferation of SK-Mel-28 human melanoma lineage cells, independently of mitochondrial membrane depolarization, apoptosis and necrosis. Moreover, 4d compound did not cause toxicity to human umbilical vein endothelial cells (HUVEC), suggesting its toxic specificity to cancer cells. [Display omitted] •Synthesis of tyrosine dipeptides.•Toxicity of a dipeptide tyrosine derivative demonstrated in a melanoma cell lineage.•Biaryl dipeptide tyrosine compounds have selective cytotoxic potential.