Synthesis, antioxidant activity and bioinformatics studies of L-3-hydroxytyrosine templated N-alkyl/aryl substituted urea/thioureas

• Published in: Bioorganic chemistry 2021-06, Vol.111, p.104837-104837, Article 104837
• Main Authors: Kollu, Umapriya, Avula, Vijaya Kumar Reddy, Vallela, Swetha, Pasupuleti, Visweswara Rao, Zyryanov, Grigory Vasilievich, Neelam, Yugandhar Sreedhar, Chamarthi, Naga Raju
• Format: Article
• Language: English
• Subjects: 1N8Q enzymatic protein; 3NRZ enzymatic protein; ADMET properties; Antioxidant activity; Bioactivity & toxicity studies; Isocyanates/Isothiocyanates; L-3-hydroxytyrosine; Molecular docking studies; QSAR studies; Urea/thiourea derivatives
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2021.104837

[Display omitted] •Employed widely available Triethylamine catalyst to synthesize urea/ thioureas.•Designed to incorporate L-3-hydroxytyrosine moiety on urea template.•The in vitro DPPH & FRAP assays revealed fluoro, chloro & nitro groups as effective.•Potential ones are also neuroprotective with 0.1788-0.7761 BBB threshold.•Isocyanate made compound as CNS active and aspartate & glutamate receptor antagonist. A new series of urea/thiourea derivatives have been efficiently synthesized from the reaction of L-3-hydroxytyrosine with selective isocyanates/isothiocyanates and characterized by Infra-red, proton & carbon-13 nuclear magnetic resonance spectral and mass spectrometry studies. All the synthesized compounds have been screened for their antioxidant activity by 1,1-diphenyl1-2-picrylhydrazyl radical assay, ferric reducing antioxidant power assay and also studied their molecular docking interaction profiles against 1N8Q and 3NRZ enzymatic proteins. The in vitro antioxidant activity has further supported by quantitative structure activity relationship, absorption, distribution, metabolism, and excretion & toxicity studies, bioactivity studies & enzyme inhibition assay and identified that they were potentially bound to ASP490 & ASP361 aminoacid residue in chain A of 1N8Q protein and GLN1194 aminoacid residue in chain L of 3NRZ protein and are responsible for potential antioxidant activity. It is proved that urea derivatives linked with 4-fluoro & 4-nitro and thiourea derivatives linked with 3-chloro & 4-fluoro have exhibited promising antioxidant activity. In eventual synthesized compounds have been identified as potential blood–brain barrier penetrable compounds and proficient central nervous system active neuro-protective antioxidant agents as they have envisaged as easily penetrable to blood–brain barrier thresholds, a neuroprotective property.