Synthesis, characterization and biological activity of new mixed ligand complexes of Zn(II) naproxen with nitrogen based ligands.

A series of novel Zn(II) complexes [Zn2(nap)4] (1), [Zn(nap)21,10-phen](2), [Zn(nap)22,9-dmphen] (3), [Zn(nap)2(2-ampy)2] (4), [Zn(nap)2(imid)2] (5), [Zn(nap)2(1,2-dmimid)2] (6) (nap = naproxen, 1,10-phen = 1,10-phenanthroline, 2,9-dmphen = 2,9-dimethyl-1,10-phenanthroline, 2-ampy = 2-aminopyridine, imid = imidazole, 1,2-dmimid = 1,2-dimethyl imidazole) were synthesized and characterized using IR, UV-Vis, (1)H NMR, (13)C{(1)H} NMR spectroscopy. The crystal structure of complex 3 was determined using single-crystal X-ray diffraction. In order to assess the effect of the metal ions on the anti-bacterial activity, complexes 1-6 have been screened in vitro, against (G(+)) bacteria (Staphylococcus aureus and Micrococcus luteus) and (G(-)) bacteria (Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis and Escherichia coli) using the agar well diffusion method. Complex 2 was the only complex that showed antibacterial activity against P. aeruginosa, where the complexation of the parent ligand 1,10-phenathroline enhanced significantly the activity. All the complexes showed different activity against the different bacteria, and were compared with activity of the parent ligands. The complexes were tested also for their anti-malarial activity using two methods: 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. This is considered an important target of many known anti-malarial drugs such as Chloroquine and Amodaquine. Results showed that the efficiency of complex 3 in preventing the formation of ß-hematin was 75%. The efficiency of Amodiaquine as a standard drug was reported to give 92.5.

New mixed ligand zinc(II) complexes based on the antiepileptic drug sodium valproate and bioactive nitrogen-donor ligands. Synthesis, structure and biological properties.

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 ß-Hematin was 80%. The efficiency of Amodiaquine as a standard drug was reported to give 91%.

HPLC separation and in vitro antimalarial studies of Artemisia annua plants from two different origins: Cameroon versus Luxembourg.

Background: Malaria is a devastating disease, particularly in Africa, due to development of resistance by Plasmodium falciparum against all known antimalarial drugs, including artemisinin. Therefore, the search for new antimalarial drugs is urgently needed, especially drugs that can impede the heme detoxification pathway in the malaria parasite, a crucial requirement for parasite survival in host erythrocytes. Materials and Methods: Water infusions of Artemisia annua plants from two different origins, Cameroon and Luxembourg, were used in this study. A semi-quantitative in vitro method, based on the inhibition of ferriprotoporphyrin IX (FP) biomineralisation developed by Deharo et al. [16], was used to reveal the differences in antimalarial activity of both plants. Reversed phase preparative liquid chromatography coupled to a photo diode array (PDA) detector was also used to test for differences in antimalarial activity. Results: Water extracts from the leaves of the Cameroon plant showed a higher potential antimalarial activity, represented by a higher ability to inhibit ß-haematin formation in vitro than A. annua extracts from Luxembourg. Although extracts of the plants of both origins showed comparable efficiencies at high concentrations, the absorbance value at 405 nm of a 10% dilution of the Cameroon plant extract was 0.075, whereas it was 1.515 for the Luxembourg plant extract. The absorbance is inversely proportional to the antimalarial activity. According to the Prep-HPLC chromatogram of the Cameroon crude sample, seven major compounds at 325 nm were found. However, only four much less pronounced compounds appeared in the Luxembourg crude sample under the same chromatographic conditions and concentration. These were preliminarily identified as polyphenolic compounds. Conclusion: A. annua infusions are widely used by people who cannot afford other treatments. Depending on the cultivation locality different chemical profiles exist. This results in differences in hemozoin formation and will therefore also lead to alterations in antimalarial activity.

Clinical experience with biphasic insulin aspart in people with type 2 diabetes: Results from the Libya cohort of the A1chieve study.

BACKGROUND: The A1chieve, a multicentric (28 countries), 24-week, non-interventional study evaluated the safety and effectiveness of insulin detemir, biphasic insulin aspart and insulin aspart in people with T2DM (n = 66,726) in routine clinical care across four continents. MATERIALS AND METHODS: Data was collected at baseline, at 12 weeks and at 24 weeks. This short communication presents the results for patients enrolled in biphasic insulin aspart sub group from Libya. RESULTS: A total of 179 patients were enrolled in the biphasic insulin aspart subgroup. All the patients were prior insulin users. At baseline glycaemic control was poor (mean HbA1c: 9.3%). After 24 weeks of treatment there was an improvement in HbA1c (-0.9%). Hypoglycaemic events reduced from 7.2 events/patient-year to 3.7 events/patient-year in 24 weeks. SADRs did not occur in any of the study patients. CONCLUSION: Starting or switching to biphasic insulin aspart was associated with improvement in glycaemic control with a low rate of hypoglycaemia.