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Volume 21, Issue 13
  • ISSN: 1570-1808
  • E-ISSN: 1875-628X

Abstract

Background

Nowadays, inflammation is recognized as the underlying cause of a number of diseases, but NSAIDs are the first drug of choice, having several side effects. Additionally, excessive cellular oxidative stress is often considered a major contributor to pathophysiological conditions, the development of cancer, and other diseases. Antimicrobial resistance is a global concern, hence, there is a critical need for the development of novel therapeutic agents to fight the emergence and increasing prevalence of resistant pathogens. This creates an initiation to introduce new molecules which act as efficient therapeutic agents with diminished side effects.

Objective

As a part of our search for newer agents with enhanced activity profiles, it was planned to synthesize novel 2- (benzamido)-N-((benzo[d][1,3]dioxol-4-yl)methylene)-3-(substituted phenyl) acrylohydrazides and to investigate them for antiinflammatory, antioxidant, cytotoxic, antimicrobial activities. Furthermore, studies were performed for title compounds to predict molecular properties, bioavailability, drug-likeness, and bioactivity scores, molecular docking studies were also performed against biological targets.

Methods

The title compounds 1-14 were synthesized by nucleophilic addition of piperonal in ethanol, few drops of acetic acid to the intermediate 2-(benzamido)-3-(aryl)acrylohydrazides. The title compounds were tested for their antiinflammatory activity by carrageenan-induced rat paw edema method, COX-2 inhibition assay; cytotoxic activity evaluation by MTT assay; antioxidant activity by Lipid peroxidation, DPPH assay, Nitric Oxide scavenging assay and Hydrogen peroxide scavenging assay; and antimicrobial activity by cup plate method. Physicochemical properties and bioactive scores of title compounds were evaluated by studies. Molecular docking studies were carried out for the title compounds against COX-2 (PDB: 5F19) and EGFR (PDB:1XKK).

Results

Among the series, 4-Hydroxy-3,5-dimethoxy derivative (5) displayed good anti-inflammatory and antioxidant activities; Vanillinyl derivative (4) displayed good cytotoxicity and antimicrobial activity when compared to that of the respective standards. Compounds 5 & 4 also exhibited good docking scores with COX-2 and EGFR, respectively. All title compounds obeyed Lipinski’s rule of five and also exhibited acceptable molecular properties, drug-likeness properties, and moderate to good bioactivity scores in studies.

Conclusion

The study suggested that the title compounds showed notable pharmacological properties, could emerge as lead compounds, and be further explored as promising therapeutic agents.

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Synthesis, Molecular Docking Studies and Biological Evaluation of N-(α-Benzamido Cinnamoyl) Piperonal Hydrazones
Letters in Drug Design & Discovery 21, 2711 (2024); https://doi.org/10.2174/1570180820666230816091339
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  • Article Type:     Research Article
Keyword(s): anticancer; antiinflammatory; antimicrobial; antioxidant; molecular docking; Piperonal

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