Crystal structure, in silico studies and anti-diabetic potentials of 3-e-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1h-pyrazol-4-yl)hyd -razinylidene]pentane-2,4-dione(hdpp)and its Cu(II) and Ni(II) complexes

Abstract

The hydrazone, 3-E-[2-(1,5-Dimethyl-3-oxo-2-Phenyl-2,3-Dihydro-1h-Pyrazol-4-yl)Hydrazinylidene]Pentane-2,4-dione, HDPP was synthesized by coupling diazotized 4-aminoantipyrine with pentan-2,4-dione at < 5 ⁰C. The Cu(II) and Ni(II) complexes were prepared by refluxing stoichiometric amounts of metal salts and HDPP in ethanol for 6 h at 60 ⁰C. The ligand and complexes were characterized by UV-Vis, IR, NMR, and mass spectroscopies as well as by C, H, N, S elemental analysis, conductivity measurement, quantitative chloride determination and single crystal X-ray diffraction analysis. The compounds were screened in vitro for antibacterial activity against P. aeruginosa, S. aureus, Ecoli(Eco 6), E. coli(13), B. subtilis, S. pneumonia, P. mirabilis, S. intermedius and K. pneumoniae. The compounds were assayed for in silico molecular docking and in vivo anti-diabetic potentials. FTIR data showed shifts in ⱱ(C=O), ⱱ(N=H) and ⱱ(C=N) of the complexes implicating the involvement of these groups in complexation. Proton NMR shifts accounted for the methyl, phenyl and N-H protons of the ligand but indecipherable for the complexes due to paramagnetic effects. Conductivity values of HDPP and complexes showed the ligand and its complexes to be neutral. X-ray crystallographic data of HDPP show the ligand to have orthorhombic crystals with pbca unit cell a = 28.501(4) Å, α = 90°, b = 15.0494(19) Å, β = 90°; and c = 7.3234(9) Å, γ = 90° with Z=8. HDPP and its complexes exist in hydrazo form instead of azo form. It showed no activity against test organisms, but the complexes showed various degrees of sensitivities against the test bacterial strain at 10μg/cm³. Acute toxicity (LD₅₀) tests showed that HDPP and [Cu(HDPP)₂Cl₂] were non-toxic. In silico studies proved them to be drug candidates for diabetes with good oral bioavailability. In vivo, antidiabetic tests showed HDPP and [Cu(HDPP)₂Cl₂] to reduce the blood level of diabetic rats to within 61 to 67% better than the control drug glibenclamide within 14 days of treatment.