title: Synthesis of copper and zinc 2-(pyridin-2-yl)imidazo[1,2-a]pyridine complexes and their potential anticancer activity.
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 IC50values 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 IC50value 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.
authors.affiliation: Molecular Sciences Institute, School of Chemistry, University of the Witwatersrand, PO Wits, 2050, South Africa. Electronic address: Jean.Dam@students.wits.ac.za.
authors.forename: Jean
authors.initials: J
authors.lastname: Dam
authors.affiliation: Division of Pharmacology, Department of Pharmacy and Pharmacology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, 2193, South Africa. Electronic address: Zeenat.Ismail@students.wits.ac.za.
authors.forename: Zeenat
authors.initials: Z
authors.lastname: Ismail
authors.affiliation: Division of Pharmacology, Department of Pharmacy and Pharmacology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, 2193, South Africa. Electronic address: t.Kurebwa@gmail.com.
authors.forename: Taurai
authors.initials: T
authors.lastname: Kurebwa
authors.affiliation: Division of Pharmacology, Department of Pharmacy and Pharmacology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, 2193, South Africa. Electronic address: Nadia.Gangat@students.wits.ac.za.
authors.forename: Nadia
authors.initials: N
authors.lastname: Gangat
authors.affiliation: Division of Pharmacology, Department of Pharmacy and Pharmacology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, 2193, South Africa. Electronic address: Leonie.Harmse@wits.ac.za.
authors.forename: Leonie
authors.initials: L
authors.lastname: Harmse
authors.affiliation: Molecular Sciences Institute, School of Chemistry, University of the Witwatersrand, PO Wits, 2050, South Africa. Electronic address: Helder.Marques@wits.ac.za.
authors.forename: Helder M
authors.initials: HM
authors.lastname: Marques
authors.affiliation: Molecular Sciences Institute, School of Chemistry, University of the Witwatersrand, PO Wits, 2050, South Africa. Electronic address: Andreas.Lemmerer@wits.ac.za.
authors.forename: Andreas
authors.initials: A
authors.lastname: Lemmerer
authors.affiliation: Molecular Sciences Institute, School of Chemistry, University of the Witwatersrand, PO Wits, 2050, South Africa. Electronic address: Moira.Bode@wits.ac.za.
authors.forename: Moira L
authors.initials: ML
authors.lastname: Bode
authors.affiliation: Molecular Sciences Institute, School of Chemistry, University of the Witwatersrand, PO Wits, 2050, South Africa. Electronic address: Charles.deKoning@wits.ac.za.
authors.forename: Charles B
authors.initials: CB
authors.lastname: de Koning
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003300:Copper / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D004355:Drug Stability; D018922:HL-60 Cells; D006801:Humans; D061986:MCF-7 Cells; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D011725:Pyridines; D003300:Copper; D015032:Zinc
keywords: Apoptosis; Breast cancer (MCF-7 and MDA-MB-231); Copper and zinc imidazo[1,2-a]pyridines; Fluorescence microscopy; Leukemia (K562 and HL-60) and colorectal cancer (HT-29); Multicomponent coupling reactions; Necrosis and paraptosis