Novel and effective peripheral tetra-substituted phthalocyanines with quinazoline groups for cancer treatment: synthesis, photophysical and photochemical properties, and in-vitro studies

Abstract

Within the scope of this study, starting from 3,4-dihydronaphthalen-1(2H)-one (1), 4-(2-amino-5,6-dihydrobenzo[h]quinazolin-4-yl)phenol (3) was synthesized in two stages according to literature. In the second step, 4-(4-(2-amino-5,6-dihydrobenzo[h]quinazolin-4-yl)phenoxy)phthalonitrile (4) was prepared as the starting ligand compound with the help of this substance for the first time. Then, novel metallophthalocyanine derivatives [2(3), 9(10), 16(17), 23(24)-Tetrakis[4-(2-amino-5,6-dihydrobenzo[h]quinazolin-4-yl)phenol] phthalocyaninato zinc(II) (5), copper (II) (6), cobalt (II) (7)] were synthesized in the presence of suitable metal salts. The structure of synthesized procersur and novel compounds were elucidated by convenient spectroscopic methods. The effect on solubility and aggregation behaviors substitution with 4-(2-amino-5,6-dihydrobenzo[h]quinazolin-4-yl)phenol from the peripheral position was investigated. The newly synthesized tetra-substituted phthalocyanines (5–7) show good solubility in common organic solvents. Also, they have no aggregation tendency between 1 and 10 µM concentrations. In addition, the photophysical and photochemical properties of substituted phthalocyanines were examined. The ability to produce 1O2 of compound (5) was 0.79 in DMSO and 0.75 in THF media. Finally, the cytotoxicity effects of the synthesized phthalonitrile (4) and its metallophthalocyanines (5–7) on MCF 7, MDA-MB-231, HT-29, C6, AGS and L-929 cells were determined by XTT (2,3bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl] 2H-tetrazolium hydroxide) method. The obtained data were compared with standard cell lines.