Affiliations 

  • 1 Department of Chemistry, Jawaharlal Nehru Technological University Anantapur, Ananthapuramu 515 002, Andhra Pradesh, India
  • 2 Department of Science & Humanities, NBKR Institute of Science & Technology, Vidyanagar 524 413, Andhra Pradesh, India
  • 3 Department of Chemistry, JNTUA College of Engineering, Pulivendula 516 390, Andhra Pradesh, India
  • 4 Department of Chemistry, Sri Venkateswara University, Tirupati 517 502, Andhra Pradesh, India
  • 5 Department of Zoology, Sri Venkateswara University, Tirupati 517 502, India; Department of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University, Chuncheon, Gangwon-Do 24341, Republic of Korea
  • 6 Centre for International Collaboration and Research, Reva University, Rukmini Knowledge Park, Bangalore 560 064, India; Department of Biomedical Sciences and Therapeutics, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Kota Kinabalu, 88400 Sabah, Malaysia; Department of Biochemistry, Faculty of Medicine and Health Sciences, Abdurrab University, Jl Riau Ujung No. 73, Pekanbaru 28292, Riau, Indonesia
  • 7 Chemical Engineering Institute, Ural Federal University, Yekaterinburg 620002, Russian Federation
  • 8 Chemical Engineering Institute, Ural Federal University, Yekaterinburg 620002, Russian Federation; Ural Division of the Russian Academy of Sciences, I. Ya. Postovskiy Institute of Organic Synthesis, 22 S. Kovalevskoy Street, Yekaterinburg 620219, Russian Federation
  • 9 Department of Chemistry, Sri Venkateswara University, Tirupati 517 502, Andhra Pradesh, India. Electronic address: csrsvu@gmail.com
Bioorg Chem, 2022 Dec;129:106205.
PMID: 36265354 DOI: 10.1016/j.bioorg.2022.106205

Abstract

Novel ethyl-4-(aryl)-6-methyl-2-(oxo/thio)-3,4-dihydro-1H-pyrimidine-5-carboxylates were synthesized from one-pot, three-component Biginelli reaction of aryl aldehydes, ethyl acetoacetate and urea/ thiourea by catalytic action of silica supported Bismuth(III) triflate, a Lewis acid. All the synthesized compounds were structurally characterized by spectral (IR, 1H NMR & 13C NMR spectroscopic and Mass spectrometric) and elemental (C, H & N) analyses. The present protocol has deserved novel as, formed the products in high yields with short reaction times, involved eco-friendly methodology and reusable heterogeneous Lewis acid catalyst. The title compounds were screened for in vitro DPPH free radical scavenging antioxidant activity and identified 4i, 4j, 4h & 4f as potential antioxidants. The obtained in vitro results were correlated with molecular docking, ADMET, QSAR, Bioactivity & toxicity risk studies and molecular finger print properties and found that in silico binding affinities were identified in good correlation with in vitro antioxidant activity and studied the structure activity relationship. The molecular docking study has disclosed strong hydrogen bonding interactions of title compounds with aspartic acid (ASP197) aminoacid residue of 2HCK, a complex enzyme of haematopoietic cell kinase and quercetin. Results of toxicology study evaluated for potential risks of compounds have revealed title compounds as safer drugs. In ultimate the study has established ligand's antioxidant potentiality as they effectively binds with ASP197 amino acid of Chain A hence confirms the inhibition of growth of reactive oxygen species in vivo. In addition, the title compounds have been identified as potential blood-brain barrier penetrable entities and efficient central nervous system (CNS) active neuro-protective antioxidant agents.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.