Synthesis and pharmacological evaluation of free-base 5,10,15,20-tetrakis(4-hydroxyphenyl)porphyrin and its Zn, Cu, Co metalloderivatives

Abstract

In this study, the 5,10,15,20-tetrakis-(4-hydroxyphenyl)porphyrin (TpOHPP) and its Zn, Cu, and Co complexes have been synthesized and evaluated as photosensitizers and for anti-inflammatory activity. TpOHPP and its Zn (Zn-TpOHPP), Cu (Cu-TpOHPP), and Co (Co-TpOHPP) ligands have been synthesised using the Alder-Longo method; their photosensitizer activity has been screened by irradiating HeLa cells with red light, comparing their relative activity to those of protoporphyrin IX (PpIX) and cisplatin (CDDP). The edema mouse model in which inflammation is induced with 12-O-tetradecanoylphorbol 13-acetate (TPA) has been adopted. Finally, molecular modeling (docking) on the test drugs have been conducted using the Autodock VINA software. TpOHPP induced time-dependent cell replication inhibition when the cells are exposed to red light (IC₅₀ = 16.35 µM, 2.3 µM, and 2.1 µM at 0, 15, and 30 minutes, respectively). Comparatively, Zn-TpOHPP exerts essentially the same cell replication inhibitory profile with and without red light exposure (IC₅₀ = 1.35 µM and 1.38 µM respectively). The percent inhibition of inflammation determined for the test molecules are 54.16% for TpOHPP, 60.38% for Zn-TpOHPP, 67.10% for Cu-TpOHPP, and 67.53% with Co-TpOHPP. TpOHPP and its Zn complex show anti-proliferative activity at low micromolar levels and the four porphyrins exerted significant anti-inflammatory activity in vivo.