Evaluation of the Molecular properties, Bioactivity Score, Pharmacokinetics and Toxicological Analysis of the Novel Quinazoline-Linked Piperazine Derivatives

Author: Patel Priteshkumar, Joshi Hirak, Patel Bhagirath and Bapna Mayank

Journal Name:

Download PDF

Abstract

Quinazoline and Piperazine derivatives have been revealed to exhibit a broad range of biological effects. As a result, substances having such a scaffold have been exploited as a lead in the design of drugs. As such, the objective of this investigation is to synthesize several quinazoline-linked piperazine analogues and execute in silico evaluations of their molecular properties, bioactivity score, pharmacokinetics, and toxicological analysis. The investigation showed that, apart from one molecular weight, the majority of the compounds fitted Lipinski's rule of five, indicating drug-likeness characteristics. The bioactivity data revealed that the N-(4-oxo-2-(4-((4-(2-(Substituted phenyl amino) acetyl) piperazin-1-yl) methyl) phenyl) quinazolin- 3(4H) - yl) benzamide derivatives were moderately active for GPCR ligand, Ion channel modulator, Kinase inhibitor, Nuclear receptor ligand, Protease inhibitor, and Enzyme inhibitor. The analysis revealed that all derivatives had the highest intestinal absorption, was not Blood Brain Barrier permeable, and was simple to remove because they could not inhibit CYP450 1A2. Using ProtTox-II, it was predicted that none of the synthesized molecules were cytotoxic and hepatotoxic. To tackle diseases with multiple drugs resistance, finding new antimicrobial drugs and improving the efficacy of those already in use through structural modification can be extremely important. The study provides information on the drug likeness, bioactivity scores, pharmacokinetics properties and toxicity of novel synthesized substances that can be employed to design and create novel anti-microbial medications that are more effective and have lower toxicity.

Keywords

Quinazolin, in silico, Pharmacokinetic, Molecular Properties, Bioactivity, Toxicity

Conclusion

In conclusion, every substance complies with Lipinski's rules for molecules' drug-likeness, except for molecular weight. All eleven compounds exhibited moderate bio-activity scores. Compounds have a moderately active for nuclear receptor ligand, kinase inhibitor, GPCR ligand, protease inhibitor, and enzyme inhibitor. All synthesized compounds, except PRP7B8, had significant levels of gastrointestinal absorption and were unable to penetrate the blood-brain barrier, according to results from in silico analyses of pharmacokinetic parameters. The CYP450 isoenzyme 1A2 metabolizes all substances, diminishing their plasma concentrations and toxicity risk. It was predicted that synthetic substances wouldn't be cytotoxic or hepatotoxic. Hence, an attempt was made to compare some specified anti-microbial medicines, such as Ciprofloxacin and Fluconazole, with the molecular properties, bioactivity score, pharmacokinetic parameters and toxicity studies of N-(4-oxo-2-(4-((4-(2-(Substituted phenyl amino) acetyl) piperazin-1-yl) methyl) phenyl) quinazolin- 3(4H)- yl) benzamide derivatives.

References

-

How to cite this article

Patel Priteshkumar, Joshi Hirak, Patel Bhagirath, Bapna Mayank (2023). Evaluation of the Molecular properties, Bioactivity Score, Pharmacokinetics and Toxicological Analysis of the Novel Quinazoline-Linked Piperazine Derivatives. Biological Forum – An International Journal, 15(4): 508-517.