Synthesis, Antibacterial, Molecular Docking, and ADEMT Studies of New Mannich Bases of Curcumin
DOI:
https://doi.org/10.21123/bsj.2024.9625Keywords:
Curcumin, Distribution, Metabolism, Molecular Docking, Toxicity.Abstract
Utilizing natural products in drug development is interesting topic for the human medical science field. In the current work, four of curcumin derivatives (M1-M4) were prepared via Mannich reaction and identified by FT-IR and NMR spectroscopy. The obtained data from in-vitro study of the compounds M1-M4 revealed convincing activities against bacteria strains including Salmonella, Staphylococcus aureus, Proteus, and Klebsiella in parallel with Amoxicillin as a standard drug. The compounds M2 and M4 have showed a high antibacterial activity. The potential DNA gyrase inhibitory activity of the compounds (M1-M4 ) was investigated via Insilco using the molecular docking simulation method. The (PyMOL) software was utilized for the calculation of the binding affinity (kcal/mol) for the prepared compounds with protein (1KZN). The highest binding values (kcal/mol) with protein was (-8.2) for M4 and (-8.1) for M2, whereas the lowest values were found (-7.1) for M1. Furthermore, the findings revealed that amino acids were linked with the synthesized compounds through hydrogen bonding and (aryne -aryne) hydrophobic interactions. Also, the linkage way between proteins and the synthesized compounds was stated via the three dimensions shape. The electronic densities of the prepared compounds were also reported through recognizing the characteristic features of amino acids, which surround these compounds. Drug-like behavior and ADMET prediction study including absorption, distribution, metabolism, excretion, and toxicity of the desired compounds were performed. The yielded results revealed that the majority of the pharmacokinetic parameters were significant and within a normal range.
Received 23/09/2023
Revised 18/12/2023
Accepted 20/12/2023
Published Online First 20/08/2024
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