Title:Synthesis, Molecular Docking Studies and Biological Evaluation of N-(α-Benzamido Cinnamoyl) Piperonal Hydrazones
Volume: 21
Issue: 13
Author(s): Karnati Saritha, Tangirala Sarala Devi, Murthi Vidya Rani, Katari Sudheer Kumar, Amineni Umamaheswari and Galla Rajitha*
Affiliation:
- Institute of
Pharmaceutical Technology, Sri Padmavati Mahila Visvavidyalayam, Tirupati, 517502, Andhra Pradesh, India
Keywords:
Piperonal, antiinflammatory, anticancer, antioxidant, antimicrobial, molecular docking.
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, in silico 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 in vivo carrageenan-induced rat paw edema
method, in vitro COX-2 inhibition assay; in vitro 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 in silico 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
in silico 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.
