Screening of in Vitro Inhibition of Lactoperoxidase Enzyme by Methyl Benzoate Derivatives with Molecular Docking Studies

Abul N., Gerni S., Korkmaz I. N., Demir Y., ÖZDEMİR H., GÜLÇİN İ.

CHEMISTRY & BIODIVERSITY, cilt.20, sa.8, 2023 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 20 Sayı: 8
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1002/cbdv.202300687
  • Dergi Adı: CHEMISTRY & BIODIVERSITY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Agricultural & Environmental Science Database, Aquatic Science & Fisheries Abstracts (ASFA), CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: enzyme inhibition, lactoperoxidase, methyl benzoate, molecular docking, AROMATIC LIGANDS, DNA-DAMAGE
  • Atatürk Üniversitesi Adresli: Evet

Özet

Lactoperoxidase enzyme (LPO) is secreted from salivary, mammary, and other mucosal glands including the bronchi, lungs, and nose, which had functions as a natural and the first line of defense towards viruses and bacteria. In this study, methyl benzoates were examined in LPO enzyme activity. Methyl benzoates are used as precursors in the synthesis of aminobenzohydrazides used as LPO inhibitors. For this purpose, LPO was purified in a single step using sepharose-4B-l-tyrosine-sulfanilamide affinity gel chromatography with a yield of 9.91 % from cow milk. Also, some inhibition parameters including the half maximal inhibitory concentration (IC50) value and an inhibition constant (K-i) values of methyl benzoates were determined. These compounds inhibited LPO with K-i values ranging from 0.033 & PLUSMN;0.004 to 1540.011 & PLUSMN;460.020 & mu;M. Compound 1 a (methyl 2-amino-3-bromobenzoate) showed the best inhibition (K-i=0.033 & PLUSMN;0.004 & mu;M). The most potent inhibitor (1 a) showed with a docking score of -3.36 kcal/mol and an MM-GBSA value of -25.05 kcal/mol, of these methyl benzoate derivatives (1 a-16 a) series are established H-bond within the binding cavity with residues Asp108 (distance of 1.79 & ANGS;), Ala114 (distance of 2.64 & ANGS;), and His351 (distance of 2.12 & ANGS;).