Applied Chemical Engineering

Synthesis, characterization, and studying the biological activity, Theoretical Study by Molecular Docking of new Derivatives from Eugenol with different drug

Sura K. Ibrahim

Department of Chemistry, College of Science for Women, University of Baghdad, Baghdad, Iraq

Maha Salih Hussein

Department of Chemistry, College of Education, University of Samarra, Samarra 34010, Iraq

Zainab Hamid Murtadha

Department of Chemistry, College of Science for Women, University of Baghdad, Baghdad, Iraq

Sana Hitur Awad

Department of Chemistry, College of Science for Women, University of Baghdad, Baghdad, Iraq

Sadeq Jaafer Al-Tameemi

Department of Pharmaceutical Chemistry, College of Pharmacy, Bilad Alrafidain University, Diyala 32001, Iraq

Mohammed Bashar Al-Qazzan

Department of Pharmaceutical Chemistry, College of Pharmacy, The University of Mashreq, Baghdad 10023, Iraq

Zahraa Mokhtar

Department of Pharmaceutical Chemistry, College of Pharmacy, Uruk University, Baghdad, Iraq

DOI: https://doi.org/10.59429/ace.v9i3.5945

Keywords: Paracetamol, Sulfamethoxazole, Phenylephrine, FTIR and H-MNR

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Abstract

For potential therapeutic uses against resistant microbial strains, this study aims to synthesize, characterize, and evaluate new (H1-H4) eugenol (2-methoxy-4-prop-2-enylphenol, 4-Allyl-2-methoxyphenol compounds, eugenol / phthalic anhydride) functionalized with medications like paracetamol, sulfamethoxazole, and phenylephrine. Due to growing antimicrobial resistance, synthesis and analytical characterization of medicinal molecules from natural sources, such as eugenol, must continue.

Methodology: For antifungal and antibacterial purposes, the compounds (H2-H4) were docked against the enzymes dihydrofolate reductase and UDP-N-acetylenolpyruvoylglucosamine reductase. The GOLD program was used to retrieve crystal structures and carry out docking. Discovery Studio Visualizer was used to study complex protein-ligand interactions. After six hours of reflux, compound H1 emerged as a reddish-brown gelatinous solid due to the interaction between phthalic anhydride and eugenol. It was necessary to activate many grams of the material H1 by treating it with the reagent SOCl₂ until the intermediate H2 was generated. H2, phenylephrine, sulfamethoxazole, and paracetamol reacted to produce H3, H4, and H5. The physical properties of the synthesized compounds, such as color and melting point ranges of 147–210°C and yield between 70% and 70%, were evaluated by laboratory researchers. The spectroscopic tests corroborated the compounds' characteristics and their medicinal potential, while a structural analysis verified the successful synthesis of the compounds.

Results: Compound H3 formed several hydrophobic and hydrogen interactions and had a high PLP fitness score to both DHFR and UDP-N-acetylenolpyruvoylglucosamine reductase (104.14 and 92.32, respectively). With the two enzymes, H2 likewise had a high PLP fitness score. The laboratory procedure effectively yielded pure chemicals H1, H2, H3, H4, and H5, according to structural confirmation using FTIR and ¹H-NMR measurements. Functional group bond vibrations through O-H, N-H, aromatic C-H, aliphatic C-H, ester C=O, amide C=O, and aromatic C=C bonds were demonstrated using FTIR spectroscopy. The accuracy of the experiments was confirmed by a number of structural integrity tests that were checked using ¹H-NMR spectroscopy. These compounds exhibited moderate to considerable antibacterial and antifungal activity against the infection-causing organisms Candida albicans, Escherichia coli, and Staphylococcus aureus, according to biological testing.

Conclusion: Eugenol and phthalic anhydride were used in the research study to create novel chemicals that were integrated with pharmaceuticals like sulfamethoxazole and paracetamol. Compound H26, which has the highest binding affinity, is the main inhibitor of the DHFR and MurB enzymes. The proper structure and purity were verified by FTIR and 1H-NMR spectroscopy. Sulfamethoxazole and phenylephrine architectures improved the compounds' antibacterial and antifungal activities against pathogenic microorganisms.

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