Investigation of the enzyme-inhibitory, antibacterial, and anticancer properties of metal phthalocyanines.

Abstract

In this study, the enzyme inhibitory, antibacterial, and anticancer activities of a phthalonitrile derivative and its metal phthalocyanines (Pcs; indium, zinc, copper, cobalt, and manganese; 1-6) were investigated. The cobalt and manganese Pcs were synthesized for the first time in this study. The inhibitory activities of the symmetric Pcs, which were expected to interact with acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) via their 4-(isopropylbenzyl)oxy substituents through host-guest interactions, were investigated. More selective inhibition of AChE than BChE was observed for these compounds. For AChE, CoPc was identified as the most potent inhibitor (IC 50 = 14.81 nM), whereas for BChE, InPc was identified as the most potent inhibitor (IC 50 = 56.35 nM). The K i values indicated that most compounds exhibited competitive inhibition; copper phthalocyanine (CuPc) showed particularly strong inhibition against AChE (K i = 3.08 nM ± 1.12), whereas the lowest K i value against BChE was observed for MnPc (K i = 25.98 ± 1.97 nM). Most compounds exhibited competitive inhibition; however, CuPc showed competitive inhibition toward AChE but a noncompetitive inhibition pattern toward BChE. Dual inhibition of AChE and BChE by these compounds may be promising for addressing cholinergic deficits associated with Alzheimer's disease. In addition, the acceptability of compounds 1-6 with respect to pharmacological drug-likeness criteria was assessed based on predicted absorption, distribution, metabolism, excretion (ADME) outcomes. In antibacterial tests, varying levels of inhibition were observed against selected bacterial strains. In anticancer assays, all compounds exhibited high cytotoxicity against the MCF-7 breast cancer cell line. Higher antiproliferative activity was observed for CuPc than for the other compounds. Morphological changes were induced in cancer cells by CuPc and MnPc. Overall, these compounds may have potential as enzyme inhibitors and as antibacterial and anticancer agents.