Designing of diamino based esterases inhibitors; synthesis, characterization, density functional theory and molecular modeling

Muhammad Asam Raza, Kiran Fatima, Zenab Saqib, Jan K. Maurin, Armand Budzianowski

Highlights

  • Six diamine based dithoic acids were proposed for esterases inhibitors.
  • The most potent molecules on the basis of theoretical studies were synthesized.
  • Both theoretical and experimental studies were in close agreement.

Keywords: Esterases; Density functional theory; Molecular docking; Dithioic acid

Abstract

Synthetic chemistry and drug design through different software is becoming more and more important nowadays. In this modern era each person is suffering from many diseases due to various factors such as financial, environmental, food etc. Proposed thiocarbamates of various diamines were synthesized hypothetically and they were docked with AChE (Acetylcholine esterase) and BChE (Butyrylcholine esterase) using MOE (Molecular Operating Environment). From results of MOE, most active (KR-25 and KR-26) were synthesized using reported methods and their structures were confirmed with Fourier-transform infrared spectroscopy, mass spectrometry and XRD (X-ray powder diffraction). Later on in-vitro enzyme inhibition studies against both targeted enzymes were screened out which also supported the docking results. The DFT (Density Functional Theory) studies were carried out for all proposed structures in the form of optimization and HOMO-LUMO calculation. ADMET (absorption, distribution, metabolism, excretion and toxicity) studies were applied on compounds in order to check their different parameters. It was concluded from docking, in-vitro enzyme inhibition and ADMET that KR-25 and KR-26 are more potent for AChE and BChE.

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