# Synthesis, Crystal Structure, Antitumor, and Antimicrobial Activity of Novel Copper(II) Complexes with a Coumarin Derivative Containing a Histamine Substituent

## TL;DR

This study creates new copper complexes with coumarin and histamine, showing strong anticancer effects, especially against liver cancer cells.

## Contribution

The paper introduces novel copper(II)–coumarin–histamine complexes with enhanced anticancer activity compared to their ligands.

## Key findings

- Copper(II) complexes showed higher anticancer activity than their corresponding ligands across all tested cancer cell lines.
- Complex 3b exhibited the strongest anticancer effect against Hep3B liver cancer cells and antimicrobial activity against S. epidermidis and S. aureus.
- Copper(II) ions were found to play a crucial role in the antitumor activity of these compounds.

## Abstract

Copper(II) complexes have great potential as antitumor and antimicrobial agents, and their coumarin derivatives bearing histamine substituents possess versatile structural and biological properties. The present article describes the synthesis of novel copper(II)–coumarin–histamine complexes and ligands and their characterization by IR, NMR, X-ray diffraction, and elemental analysis. Their antimicrobial activity (MIC, MBC/MFC) was tested against 11 reference strains. Cytotoxicity was evaluated using the MTT assay against 15 selected cancer cell lines and normal HMEC-1 cells. It presents three new ligands and three new complexes with copper(II) ions and selected histamine-containing coumarin derivatives. The new copper(II) complexes demonstrated markedly higher anticancer activity than their corresponding ligands across all evaluated cancer cell lines. The highest anticancer activity against the Hep3B liver cancer cell line was demonstrated by the copper(II) complex (3b), which also showed the strongest inhibition of S. epidermidis ATCC 12228 and S. aureus ATCC 6538. The copper(II) ions play a crucial role in the antitumor activity of these derivatives. Despite limited antimicrobial effects, the tested complexes, particularly 3a and 3b, demonstrate promising anticancer potential, especially against the Hep3B cancer cell line. Only 3b demonstrated antimicrobial activity against S. epidermidis ATCC 12228 and S. aureus ATCC 6538.