Physicochemical Properties and Photodynamic Activity of Novel Derivatives of Triarylmethane and Thiazine

• Published in: Archiv der Pharmazie (Weinheim) Vol. 346; no. 4; pp. 255 - 265
• Main Authors: Montes de Oca, María N., Vara, Jimena, Milla, Laura, Rivarola, Viviana, Ortiz, Cristina S.
• Format: Journal Article
• Language: English; German
• Published: Weinheim WILEY-VCH Verlag 01.04.2013; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Subjects: Animals; Azure B; Bromination; Cell Line, Tumor; Chemistry; Chemistry, Medicinal; Chemistry, Multidisciplinary; Drug Stability; Dyes; Female; Hydrophobic and Hydrophilic Interactions; Life Sciences & Biomedicine; Mammary Neoplasms, Animal - drug therapy; Mammary Neoplasms, Animal - pathology; Methane - chemical synthesis; Methane - chemistry; Methane - pharmacology; New Fuchsin; Pharmacology & Pharmacy; Photochemotherapy - methods; Photodynamic activity; Photosensitizing Agents - chemical synthesis; Photosensitizing Agents - chemistry; Photosensitizing Agents - pharmacology; Physical Sciences; Physicochemical properties; Science & Technology; Structure-Activity Relationship; Thiazines - chemical synthesis; Thiazines - chemistry; Thiazines - pharmacology; PHASE LIQUID-CHROMATOGRAPHY; METHYLENE-BLUE; Photodynamic activity; DYES; Bromination; PHOTOSENSITIZERS; MITOCHONDRIA; SELF-AGGREGATION; THERAPY; New Fuchsin; CRYSTAL VIOLET; Azure B; Physicochemical properties; SELECTIVE PHOTOTOXICITY; LIPOPHILICITY
• ISSN: 0365-6233; 1521-4184
• DOI: 10.1002/ardp.201200437

Triarylmethane and thiazine dyes have attracted attention as anticancer and antimicrobial agents, due to their structural features and selective localizations. Although these dyes have been initially explored in the context of photodynamic therapy, some of these such as New Fuchsin and Azure B have still not been extensively investigated. For this reason, we evaluated the chemical stability, aggregation effect, and lipophilicity, as well as the photodynamic activity against LM‐2 murine mammary carcinoma cells of five new brominated dyes of triarylmethane and thiazine. These cationic compounds were obtained at high purities and unequivocally characterized by conventional techniques. The introduction of bromine atoms into the chromophoric system of New Fuchsin and Azure B dyes gave rise to a moderate bathochromic shift and increased the lipophilicity, thereby improving their photophysical and photochemical properties for biomedical applications. Moreover, the in vitro photodynamic activity demonstrated that, as the degree of bromination increased, the phototoxicity remained unchanged or decreased. The lower efficiency to inactivate cultured tumor cells may be attributed to the formation of the colorless carbinol pseudobase and aggregation effects for triarylmethane and thiazine dyes, respectively. A promising strategy to reverse the biological activity decrease observed might be the design of third‐generation photosensitizers. The chemical stability, aggregation effect, and lipophilicity, as well as the photodynamic activity of five new brominated dyes of New Fuchsin and Azure B were evaluated. These compounds presented a moderate bathochromic shift and increased lipophilicity, but their photocytotoxicity remained unchanged or decreased. This behavior may be attributed to the instability or aggregation of the compounds, which could be reversed through the design of third‐generation photosensitizers.