Novel phenolic Mannich base derivatives: synthesis, bioactivity, molecular docking, and ADME-Tox Studies


TOKALI F. S. , Taslimi P., Demirciolu I. H. , Sendil K., TÜZÜN B., GÜLÇİN İ.

JOURNAL OF THE IRANIAN CHEMICAL SOCIETY, 2021 (Journal Indexed in SCI) identifier identifier

  • Publication Type: Article / Article
  • Volume:
  • Publication Date: 2021
  • Doi Number: 10.1007/s13738-021-02331-8
  • Title of Journal : JOURNAL OF THE IRANIAN CHEMICAL SOCIETY

Abstract

In this study, it was aimed to synthesize novel molecules containing potential biological active phenolic Mannich base moiety and evaluate the inhibition properties against alpha-glycosidase (alpha-Gly) and acetylcholinesterase (AChE). For this purpose, phenolic aldehydes (1-3) were synthesized from 4-hydroxy-3-methoxy benzaldehyde (vanillin) according to the Mannich Reaction. Five different carboxylic acid hydrazides (4a-e) were synthesized from esters obtained from carboxylic acids. Fifteen Schiff base derivatives (5a-e, 6a-e, and 7a-e) were synthesized from the condensation reaction of compounds 1-3 with 4a-e. In this work, a series of novel Schiff bases from Phenolic Mannich bases (5a-e, 6a-e, and 7a-e) were tested toward alpha-Gly and AChE enzymes. Compounds 5a-e, 6a-e, and 7a-e showed Kis in ranging of 341.36 +/- 31.84-904.76 +/- 93.56 nM on AChE and 176.27 +/- 22.87-621.77 +/- 69.98 nM on alpha-glycosidase. Finally, novel compounds were found using molecular docking method to calculate the biological activity of these bases against many enzymes. The enzymes used in these calculations are acetylcholinesterase and alpha-glycosidase, respectively. Molecule 6b is more effective and active than other molecules with a docking score parameter value of - 8.77 against AChE enzyme and 6d is more effective and active than other molecules with a docking score parameter value of - 4.94 against alpha-Gly enzyme. After calculating the biological activities of novel compounds, ADME/T analysis parameters were examined to calculate the future drug use properties.