title: Copper(ii) mixed-ligand polypyridyl complexes with doxycycline - structures and biological evaluation.
abstract: Mixed-ligand Cu(ii) complexes of the type [Cu(doxycycline)(L)(H2O)2](NO3)2, where doxycycline = [4-(dimethylamino)-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide] and L = 2,2'-bipyridine (bpy, 1), 1,10-phenanthroline (phen, 2), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq, 3) and dipyrido[3,2-a:2',3'-c]phenazine (dppz, 4) have been synthesised and characterised by structural, analytical, and spectral methods. The single-crystal X-ray structures of 1 and 2 exhibited two different geometries, distorted square-pyramidal and octahedral respectively as well as different coordination modes of doxycycline. Complexes 2-4 exhibit prominent plasmid DNA cleavage at significantly low concentrations probably by an oxidative mechanism. Matrix Metalloproteinase (MMP-2) inhibition studies revealed that all complexes inhibit MMP-2 similar to doxycycline which is a well-known MMP inhibitor with 3 being the most potent. IC50 values of doxycycline and 1-4 against MCF-7 (human breast cancer) and HeLa cell lines were almost equal in which 3 showed the highest efficiency (IC50 = 0.46 ± 0.05 μM), being consistent with its increased MMP inhibition potency. The antimalarial activities of these complexes against the chloroquine-sensitive Plasmodium falciparum NF54 and chloroquine-resistant Plasmodium falciparum Dd2 strains reveal that complex 3 exhibited a higher activity than artesunate drug against the chloroquine-resistant Dd2 strain.
authors.affiliation: Department of Chemistry, Savitribai Phule Pune University, Pune-411007, India. askum@chem.unipune.ac.in.
authors.forename: Olufunso O
authors.initials: OO
authors.lastname: Abosede
authors.forename: Nilima A
authors.initials: NA
authors.lastname: Vyas
authors.forename: Sushma B
authors.initials: SB
authors.lastname: Singh
authors.forename: Avinash S
authors.initials: AS
authors.lastname: Kumbhar
authors.forename: Anup
authors.initials: A
authors.lastname: Kate
authors.forename: Anupa A
authors.initials: AA
authors.lastname: Kumbhar
authors.forename: Ayesha
authors.initials: A
authors.lastname: Khan
authors.forename: Andrea
authors.initials: A
authors.lastname: Erxleben
authors.forename: Peter
authors.initials: P
authors.lastname: Smith
authors.forename: Carmen
authors.initials: C
authors.lastname: de Kock
authors.forename: Frank
authors.initials: F
authors.lastname: Hoffmann
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Obaleye
mesh_terms: D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D053837:DNA Cleavage / Q000187:drug effects; D004318:Doxycycline / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D061965:Matrix Metalloproteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects; D011725:Pyridines / Q000737:chemistry*
chemical_list: D000962:Antimalarials; D000970:Antineoplastic Agents; D056831:Coordination Complexes; D008024:Ligands; D061965:Matrix Metalloproteinase Inhibitors; D011725:Pyridines; D003300:Copper; D004318:Doxycycline