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

Authors

  • Ndidiamaka Justina Agbo Sheda Science and Technology Complex, Abuja, Nigeria
  • Pius Oziri Ukoha University of Nigeria, Nsukka, 410001, Nigeria
  • Uchechukwu Susan Oruma University of Nigeria, Nsukka, 410001, Nigeria.
  • Oguejiofo Theophilus Ujam University of Nigeria, Nsukka, 410001, Nigeria
  • Tania Groutso University of Auckland, Private Bag 92019, Auckland1142 New Zealand.
  • Solomon Ejike Okereke Abia State University, Uturu, Abia State

Keywords:

Hydrazone, X- ray crystallography, Co(II), Ni(II), Cu(II) and Fe(III) complexes, In silico and antidiabetic studies

Abstract

Communication in Physical Sciences, 2024, 11(3): 589-606

Authors: Ndidiamaka. Justina Agbo, Pius Onyeoziri  Ukoha, Uchechukwu Susan Oruma*, Oguejiofo T.  Ujam, Tania Groutso, Okereke Solomon Ejike

Received: 02 April 2024/Accepted: 06 July 2024

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.

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Author Biographies

Pius Oziri Ukoha, University of Nigeria, Nsukka, 410001, Nigeria

Department of Pure and Industrial Chemistry

Uchechukwu Susan Oruma, University of Nigeria, Nsukka, 410001, Nigeria.

Department of Pure and Industrial Chemistry

Oguejiofo Theophilus Ujam, University of Nigeria, Nsukka, 410001, Nigeria

Department of Pure and Industrial Chemistry

Tania Groutso, University of Auckland, Private Bag 92019, Auckland1142 New Zealand.

School of Chemical Sciences

Solomon Ejike Okereke, Abia State University, Uturu, Abia State

Department of Industrial Chemistry

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2023-07-23

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Vol. 11 No. 4 (2024): VOLUME 11 ISSUE 4

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