Synthesis, Structure and Cytotoxic Properties of Copper(II) Complexes of 2-Iminocoumarins Bearing a 1,3,5-Triazine or Benzoxazole/Benzothiazole Moiety

Abstract

A series of copper(II) complexes of 2-imino-2H-chromen-3-yl-1,3,5-triazines 2a-h, 3-(benzoxazol-2-yl)-2H-chromen-2-imines 4a-b, and 3-(benzothiazol-2-yl)-2H-chromen-2-imines 6a-c were obtained by reacting of appropriate 2-iminocoumarin ligands L1a-h, L3a-b, and L5a-c with 3-fold molar excess of copper(II) chloride. The structure of these compounds was confirmed by IR spectroscopy, elemental analysis, and single-crystal X-ray diffraction data (2f, 2g, 2h, and 6c). All the synthesized complexes were screened for their activity against five human cancer cell lines: DAN-G, A-427, LCLC-103H, SISO, and RT-4 by using a crystal violet microtiter plate assay and relationships between structure and in vitro cytotoxic activity are discussed. The coordination of 2-iminocoumarins with copper(II) ions resulted in complexes 2a-h, 4a-b, and 6a-c with significant inhibitory properties toward tested tumor cell lines with IC50 values ranging from 0.04 μM to 15.66 μM. In comparison to the free ligands L1a-h, L3a-b, and L5a-c, the newly prepared Cu(II) complexes often displayed increased activity. In the series of copper(II) complexes of 2-imino-2H-chromen-3-yl-1,3,5-triazines 2a-h the most potent compound 2g contained a 4-phenylpiperazine moiety at position 6 of the 1,3,5-triazine ring and an electron-donating diethylamino group at position 7′ of the 2-iminocoumarin scaffold. Among the Cu(II) complexes of 3-(benzoxazol-2-yl)-2H-chromen-2-imines 4a-b and 3-(benzothiazol-2-yl)-2H-chromen-2-imines 6a-c the most active was benzoxazole-2-iminocoumarin 4b that also possessed a diethylamino group at position 7′ of the 2-iminocoumarin moiety. Moreover, compound 4b was found to be the most prominent agent and displayed the higher potency than cisplatin against tested cell lines.

Crystal structure of 3-(benzo[d]thiazol-2-yl)-6-methyl-2H-chromen-2-one

“…Some decades ago, we reported the syntheses and characterizations of novel coumarin derivatives that have found applications as laser dyes (Elgemeie, 1989); these included 3-(benzo[d]thiazol-2-yl)-2H-chromen-2-one, the desmethyl analogue of title compound 4, a benzothiazole-based coumarin derivative which was synthesized by the reaction of 2-(cyanomethyl)benzothiazole with salicyaldehyde. Afterwards, other research groups utilized essentially the same reaction to synthesize different derivatives of the same heterocyclic framework, including compound 4 (Chao et al, 2010;Makowska et al, 2019).…”

Synthesis and biological evaluation of novel benzothiazole derivatives as potential anticancer and antiinflammatory agents

“…Over the past two decades, benzothiazole compounds have attracted considerable research attention due to their distinctive structure and diverse biological activities, including anti-tumor (Kamal et al, 2010;Kamal et al, 2011;El-Helby et al, 2019;Makowska et al, 2019;Mokesch et al, 2020), anti-inflammatory (Lee et al, 2011;Kumar and Singh, 2021), neuroprotective (Choi et al, 2007), antibacterial (Al-Tel et al, 2011;Racané et al, 2020), and antiparasitic (Awadh, 2023) activities, etc. In recent years, extensive research has focused on modifying the benzothiazole nucleus to enhance its anti-tumor activities.…”

Multifaceted Chiral Probe 2,3-Dihydro-4-hydroxy-chromene Schiff Base in Detecting Cu2+ Ions, l-Histidine, and Indazole: Spectroscopic Investigation and Confocal and Live Cell Imaging

“…10 Copper has excellent redox/binding properties and forms stable complexes with the ligands having rich donor sites (oxygen, sulfur, and nitrogen atoms). 11 According to WHO, the presence of cupric ions must be below 31.4 μM in drinking water. 12 Hence, suitable sensors have to be developed for the detection of copper ions (Cu(I)/Cu(II)) in organic and environment samples.…”

“…. Copper has excellent redox/binding properties and forms stable complexes with the ligands having rich donor sites (oxygen, sulfur, and nitrogen atoms) . According to WHO, the presence of cupric ions must be below 31.4 μM in drinking water .…”