Cancer photocytotoxicity and anti-inflammatory response of cis-A2B2 type meso-p-nitrophenyl and p-hydroxyphenyl porphyrin and its zinc(ii) complex: a synthetic alternative to the THPP synthon

Abstract

This work establishes that in comparison with the popular synthetic synthon tetra-p-hydroxyphenyl porphyrin (THPP), used for developing various cancer photodynamic therapy (PDT) agents, the cis-A₂B₂ type porphyrin derivative, synthesized by replacing two p-hydroxyphenyl groups at the meso-positions with two p-nitrophenyl moieties, 5,10-bis-(4-hydroxyphenyl)-15,20-bis-(4-nitrophenyl)porphyrin PN₂(OH)₂ and its zinc(II) complex PN₂(OH)₂Zn have more promising photosensitizing and photobiological activities. The presence of the electron-withdrawing p-nitrophenyl moiety seems to strengthen and influence the photodynamic therapy (PDT) action against the A549 cell line by upregulating reactive oxygen species (ROS) and downregulating superoxide dismutase (SOD) in the same cancer cell line. Further, murine macrophage myeloperoxidase (MPO) inhibition and nitric oxide (NO) downregulation by PN₂(OH)₂ and PN₂(OH)₂Zn are indicative of a concomitant immunoprotective nature towards noncancerous cells.