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.

Synthesis, characterization and antibacterial susceptibility testing of manganese complexes of doxycyline with bipyridine and phenanthroline

“…The results of the elemental analyses are in accordance with the proposed formula: The infrared spectra of the complexes were compared to that of the ligand and were assigned based on previous published report [21]. The stretching frequency of doxycycline hydroxyl shifted from 3452 to 3508 cm -1 in complexes 1 and 2 and 3512 cm -1 in complex 3, a shift of 46 cm -1 for complexes 1 and 2 and 60 cm -1 for complex 3.…”

“…The new absorptions at 434, 435 and 436 cm -1 ; 497, 499 and 499 cm -1 ; and at 563, 565 and 584 cm -1 in complexes 1, 2 and 3 respectively are attributed to Mn-O bond while the ones at 459 in complexes 2 and 3 are attributed to Mn-N bond. Similar coordination mode has been proposed for 1:1 copper complex of doxycycline [21]. b.…”

“…In our continuous effort to investigate the effect of complexation of metal ions to biologically relevant ligands [21][22][23][24][25], we have synthesized manganesedoxycycline complex and mixed doxycycline manganese complexes with bipyridine and phenanthroline and characterized them by FT-IR, elemental analysis and electrospray mass spectroscopy. The rationale was based on the aforementioned vital roles manganese and its compounds play in biological systems, and the pleiotropic properties of tetracyclines.…”

DNA Binding Studies of Ternary Copper (II) Complexes of Doxycycline with Polypridyl Ligands

“…All other chemicals and reagents are of analytical grade and used without further purifications. The metal complexes were synthesized according to previous published reports [69]. UV-Vis absorption measurements were carried out on Jasco V-630 spectrophotometer.…”

Fe(III)-doxycycline complexes with diimine ligands: Syntheses, characterization and biological properties

“…Herein, we report spectroscopic analyses of the complexes, their antibacterial potentials against Staphylococcus aureus and Klebsiella pneumonia strains, their antiplasmodial activity and their interaction with calf thymus DNA (CT DNA) as evidenced by electronic titration of complexes 2 and 3. This work is part of our effort targeted towards synthesizing metal complexes of biologically relevant ligands for various antibacterial and antimalarial applications, [30][31][32][33].…”