Amino Acid Derivatives of Chlorin-e6—A Review

• Published in: Molecules (Basel, Switzerland) Vol. 28; no. 8; p. 3479
• Main Authors: Vicente, Maria da Graça H., Smith, Kevin M.
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 14.04.2023; MDPI
• Subjects: amino acid conjugate; Apoptosis; Aspartic acid; Carboxylic acids; Chemistry; chlorin-e6; Chlorophyll; Chromatography; Clinical trials; Conformation; Conjugates; Crystallography; Light; LS-11; Molecular conformation; NPe6; Photodynamic therapy; Reagents; Review; Single crystals; Talaporfin; Tumors; X-ray crystallography; United States > US; Mexico
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules28083479

Details of the structural elucidation of the clinically useful photodynamic therapy sensitizer NPe6 (15) are presented. NPe6, also designated as Laserphyrin, Talaporfin, and LS-11, is a second-generation photosensitizer derived from chlorophyll-a, currently used in Japan for the treatment of human lung, esophageal, and brain cancers. After the initial misidentification of the structure of this chlorin-e6 aspartic acid conjugate as (13), NMR and other synthetic procedures described herein arrived at the correct structure (15), confirmed using single crystal X-ray crystallography. Interesting new features of chlorin-e6 chemistry (including the intramolecular formation of an anhydride (24)) are reported, allowing chemists to regioselectively conjugate amino acids to each available carboxylic acid on positions 131 (formic), 152 (acetic), and 173 (propionic) of chlorin e6 (14). Cellular investigations of several amino acid conjugates of chlorin-e6 revealed that the 131-aspartylchlorin-e6 derivative is more phototoxic than its 152- and 173-regioisomers, in part due to its nearly linear molecular conformation.