IN SILICO, PREPARATION AND IN VITRO STUDIES OF BENZYLIDENE-BASED HYDROXY BENZYL UREA DERIVATIVES AS FREE RADICAL SCAVENGERS IN PARKINSON’S DISEASE

JAGDISH CHAND; AMARJITH THIYYAR KANDY; KAVERI PRASAD; JINU MATHEW; FARHATH SHERIN; GOMATHY SUBRAMANIAN

doi:10.22159/ijap.2024v16i3.50628

Authors

JAGDISH CHAND Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty-643001, The Nilgiris, Tamil Nadu, India https://orcid.org/0000-0003-3317-9927
AMARJITH THIYYAR KANDY Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty-643001, The Nilgiris, Tamil Nadu, India https://orcid.org/0009-0008-8190-9473
KAVERI PRASAD Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty-643001, The Nilgiris, Tamil Nadu, India
JINU MATHEW Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty-643001, The Nilgiris, Tamil Nadu, India https://orcid.org/0000-0002-3649-6621
FARHATH SHERIN Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty-643001, The Nilgiris, Tamil Nadu, India https://orcid.org/0000-0002-8608-2320
GOMATHY SUBRAMANIAN Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty-643001, The Nilgiris, Tamil Nadu, India

DOI:

https://doi.org/10.22159/ijap.2024v16i3.50628

Keywords:

Molecular docking, Free radical scavengers, SHSY-5Y neuroblastoma cells, In vitro, Parkinson’s disease

Abstract

Objective: The study focuses on the benzylidene-based hydroxy benzyl urea derivative as free radical scavengers in PD.

Methods: The derivatives were designed, synthesized, and characterized using FTIR, ¹H, ¹³C-NMR, and Mass spectrometry. Further in vitro studies were performed on the SHSY-5Y cell lines. Molecular docking and molecular dynamic studies were performed at 100 ns to predict the binding affinity and stability of the ligand/protein complex.

Results: Among the nine derivatives, compounds HBU-2, and HBU-4were found to have the highest binding affinity-9.699 kcal/mol, and-9.020 kcal/mol with the amino acid interactions SER 149, PHE 157, ARG 158, SER 159, ILE 230, and ASP 231. Further, this HBU-1 to HBU-9 derivatives were produced using a synthesis route. The neurotoxicity studies were performed on the SHSY-5Y cells, where the % cell viability for the compound HBU-2, and HBU-4 was 91.22 %, and 90.42 %at a minimal concentration of 125 µg/ml with a p-value<0.011. Further, the cell counts and LDH assay for the compound HBU-2, and HBU-4 with MPP⁺treatment predicted 0.72-fold change and 0.66-fold change. The ROS % activity was also measured for compounds HBU-2 and HBU-4 in conjunction with the MPP⁺induction. In the SHSY-5Y cell line, compound HBU-2 downregulated the ROS level to 45%.

Conclusion: The synthesized compounds were found to have good free radical scavenging properties on SHSY-5Y neuroblastoma cell lines, considering these derivatives could be further assessed using appropriate PD models.

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