title: New mixed ligand zinc(II) complexes based on the antiepileptic drug sodium valproate and bioactive nitrogen-donor ligands. Synthesis, structure and biological properties.
abstract: Starting from the precursor [Zinc Valproate complex] (1), new mixed ligand zinc(II) complexes of valproic acid and nitrogen-based ligands, formulating as, [Zn(valp)22,9-dmphen] (2), [Zn2(valp)4(quin)2] (3), [Zn(valp)2(2-ampy)2] (4), and [Zn(valp)2(2-ampic)2] (5) (valp = valproate, 2,9-dmphen = 2,9-dimethyl-1,10-phenanthroline, quin = quinoline, 2-ampy = 2-aminopyridine, 2-ampic = 2-amino-6-picoline) were synthesized and characterized using IR, (1)H NMR, (13)C{(1)H} NMR and UV-Vis spectrometry. The crystal structures of complexes 2, 3 and 4 were determined using single-crystal X-ray diffraction. The complexes were also evaluated for their anti-bacterial activity using in-vitro agar diffusion method against three Gram-positive (Micrococcus luteus, Staphylococcus aureus, and Bacillus subtilis) and three Gram-negative (Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis) species. Complex 2 showed considerable activity against all tested microorganisms and the effect of complexation on the anti-bacterial activity of the parent ligand of 2 was also investigated. The anti-bacterial activity of 2,9-dmphen against Gram-negative bacteria was enhanced upon complexation with zinc valproate. On the other hand, complexes 1 and 3 showed weak inhibition activity against the tested species and complexes 4 and 5 didn't show any activity at all. Two methods were used for testing the inhibition of ferriprotoporphyrinIX bio-mineralization: a semi-quantitative micro-assay and a previously self-developed quantitative in-vitro method. Both were used to study the efficiency of these complexes in inhibiting the formation of the Malaria pigment which considered being the target of many known anti-malarial drugs such as Chloroquine and Amodiaquine. Results showed that the efficiency of complex 2 in preventing the formation of β-Hematin was 80%. The efficiency of Amodiaquine as a standard drug was reported to give 91%.
authors.affiliation: Department of Chemistry, Birzeit University, P.O. Box 14, West Bank, Palestine.
authors.forename: Mohanad
authors.initials: M
authors.lastname: Darawsheh
authors.affiliation: Department of Chemistry, Birzeit University, P.O. Box 14, West Bank, Palestine. Electronic address: habuali@birzeit.edu.
authors.forename: Hijazi
authors.initials: H
authors.lastname: Abu Ali
authors.affiliation: Department of Chemistry, Birzeit University, P.O. Box 14, West Bank, Palestine.
authors.forename: A Latif
authors.initials: AL
authors.lastname: Abuhijleh
authors.affiliation: Department of Biology and Biochemistry, Birzeit University, West Bank, Palestine.
authors.forename: Emilia
authors.initials: E
authors.lastname: Rappocciolo
authors.affiliation: Department of Life Sciences, Al-Quds University, West Bank, Palestine.
authors.forename: Mutaz
authors.initials: M
authors.lastname: Akkawi
authors.affiliation: Department of Life Sciences, Al-Quds University, West Bank, Palestine.
authors.forename: Suhair
authors.initials: S
authors.lastname: Jaber
authors.affiliation: Department of Chemistry, Birzeit University, P.O. Box 14, West Bank, Palestine.
authors.forename: Salam
authors.initials: S
authors.lastname: Maloul
authors.affiliation: Department of Biology and Biochemistry, Birzeit University, West Bank, Palestine.
authors.forename: Yasmeen
authors.initials: Y
authors.lastname: Hussein
mesh_terms: D000631:Aminopyridines / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D006420:Hemeproteins / Q000037:antagonists & inhibitors*; D008024:Ligands; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010618:Phenanthrolines / Q000737:chemistry; D010847:Picolines / Q000737:chemistry; D011804:Quinolines / Q000737:chemistry; D013329:Structure-Activity Relationship; D014635:Valproic Acid / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015032:Zinc / Q000737:chemistry
chemical_list: D000631:Aminopyridines; D000900:Anti-Bacterial Agents; D000927:Anticonvulsants; D000962:Antimalarials; D006420:Hemeproteins; D008024:Ligands; D009942:Organometallic Compounds; D010618:Phenanthrolines; D010847:Picolines; D011804:Quinolines; C020753:hemozoin; D014635:Valproic Acid; C002701:neocuproine; C037219:quinoline; D015032:Zinc; C032439:alpha-aminopyridine
keywords: Anti-bacterial activity; Anti-malarial activity; Hemozoin; Nitrogen-based ligands; Valproic acid; Zinc(II) complexes; β-Hematin