In-silico and in-vivo antidiabetic studies of hydrazone, derived from 4-aminoantipyrine and 1,3-diphenylpropane-1,3-dione (HPDP) and its co(ii) and cu(ii) complexes
This investigation assesses the in silico molecular interactions against target proteins, in silico binding affinity of HPDP and its metal complexes against specific molecular targets. toxicity, and antidiabetic potential of 3-[-2-(1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)hydrazylidine]-1,3-diphenylpropane-1,3-dione] (HPDP) and its Co(II) and Cu(II) complexes, represented as [Co(PDP)2] and [Cu(HPDP)2Cl2] respectively. Acute toxicity investigation was carried out to identify compounds with low toxicity, for in-silico analysis and in-vivo studies for potential antidiabetic benefits. The two pharmacological targets used were acetylcholinesterase (3LII) and fructose-1,6-biphosphatese (2JJK). A single intraperitoneal dose of 140 mg/kg of alloxan was used to induced diabetes in the experimental Abino rats (120 mg/kg body weight). Rats were divided into nine groups: control (A), diabetic control group (B), diabetic group (C) receiving glibenclamide treatment. The treatment groups (1A, 1B; 2A, 2B and 3A, 3B) received, for a period of 14 days, low and high doses (200 and 400 mg/kg of body weight) HPDP, [Co(PDP)2] and [Cu(HPDP)2Cl2] compounds, respectively. In silico molecular docking showed promising binding interactions with important one antidiabetic target. Within 14 days of therapy, the results showed that HPDP, [Co(PDP)2], [Cu(HPDP)2Cl2], and glibenclamide (standard control) decreased the blood glucose levels of the experimental rats by 74.08%, 36.55%, 70.53%, and 60.56 %, respectively. These results imply that these compounds could make interesting candidates for treatments of diabetes.
Keywords: Acute toxicity, Complex, Diabetes, Hydrazone and Molecular docking
*Correspondence: agbo.ndj@gmail.com, 08057284501
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