Photodynamic evaluation of triazine appended porphyrins as anti-leishmanial and anti-tumor agents

Abstract

Many recent advancements in porphyrin based photodynamic therapy are being treated as revolutionary in the field of medicinal chemistry, as they offer effective and viable solutions for many serious diseases including cancer. Motivated by the exceptional bioactivity of triazine moieties, we designed 4,6-diamino-1,3,5-triazine appended 5,10,15,20-tetrakis(4-hydroxyphenyl)porphyrin (THP) and it's metal derivatives; adopting a mild and effective microwave assisted protocol. All the synthesized derivatives were evaluated in-vitro for their anti-proliferative activity against human malignant melanoma (A375), human breast cancer (MCF-7) and promastigote form of Leishmania donovaniby MTT assay in the presence of light. The study revealed better inhibitory activity of the derivatives under illumination, compared to the parent compound. The compounds were found to be non-toxic to normal cells at their respective concentrations of anti-proliferative action, in both dark and light. The cellular uptake of the compounds in tumor cell was confirmed using laser confocal fluorescence microscopy. In order to establish the mechanism of action, the singlet oxygen generation efficiency was also investigated. The superior inhibitory activity of the zinc derivative has been indicated by its highest singlet oxygen generation efficiency (ΦΔ = 0.69).