1. Synthesis of copper and zinc 2-(pyridin-2-yl)imidazo[1,2-a]pyridine complexes and their potential anticancer activity
- Author
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Moira L. Bode, Charles B. de Koning, Nadia Gangat, Taurai Kurebwa, Leonie Harmse, Andreas Lemmerer, Zeenat Ismail, Jean Dam, and Helder M. Marques
- Subjects
Stereochemistry ,Pyridines ,chemistry.chemical_element ,Antineoplastic Agents ,Apoptosis ,HL-60 Cells ,Zinc ,010402 general chemistry ,01 natural sciences ,Medicinal chemistry ,Paraptosis ,chemistry.chemical_compound ,Drug Stability ,Drug Discovery ,Pyridine ,medicine ,Organometallic Compounds ,Humans ,Cell Proliferation ,Pharmacology ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Acridine orange ,General Medicine ,Copper ,0104 chemical sciences ,MCF-7 Cells ,Drug Screening Assays, Antitumor ,Ethidium bromide ,Camptothecin ,medicine.drug - Abstract
A small library of novel copper and zinc imidazo[1,2-a]pyridine complexes have been synthesized. Their structures were confirmed by X-ray diffraction crystallography and a selection of these compounds was tested against five cancer cell lines originating from breast cancer (MCF-7 and MDA-MB-231), leukemia (K562 and HL-60) and colorectal cancer (HT-29). The imidazo[1,2-a]pyridines and their zinc complexes showed poor anticancer activity, while the copper complexes were active against the cancer cell lines with IC50 values comparable to and lower than camptothecin. For example, copper 6-bromo-N-cyclohexyl-2-(pyridin-2-yl)imidazo[1,2-a]pyridin-3-amine acetate 21 had an IC50 value lower than 1 μM against the HT-29 cells. Fluorescence microscopy with acridine orange, Hoechst 33342 and ethidium bromide, used in a preliminary investigation to evaluate morphological changes showed that copper 6-bromo-N-cyclohexyl-2-(pyridin-2-yl)imidazo[1,2-a]pyridin-3-amine acetate 21 caused both apoptosis, necrosis and paraptosis in the MCF-7 and HL-60 cells. A select group of copper N-cyclohexyl-2-(pyridin-2-yl)imidazo[1,2-a]pyridin-3-amines (26, 27, 29 and 31) induced apoptosis, paraptosis and deformed nuclei in MCF-7 cells.
- Published
- 2016