مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
Investigating the potential of inhibiting Klebsiella pneumoniae beta-lactamase using the compounds identified by the GC-Mass method in the essential oil of Mentha pulegium based on the crystal structure of OXA-48 through molecular docking methods and investigating the toxicity and medicinal properties of the compounds. identified with the highest affinity to the OXA-48 protein structure
Investigating the potential of inhibiting Klebsiella pneumoniae beta-lactamase using the compounds identified by the GC-Mass method in the essential oil of Mentha pulegium based on the crystal structure of OXA-48 through molecular docking methods and investigating the toxicity and medicinal properties of the compounds. identified with the highest affinity to the OXA-48 protein structure
Hasan Naeinizade Labaf,1 Forouzan Absalan,2,*Mostafa Jamalan,3Ehsan Ghasemi,4Armin Khaleghjoo,5
1. Medical Faculty, Abadan University of Medical Sciences, Abadan, Iran 2. Medical Faculty, Abadan University of Medical Sciences, Abadan, Iran 3. Medical Faculty, Abadan University of Medical Sciences, Abadan, Iran 4. Medical Faculty, Abadan University of Medical Sciences, Abadan, Iran 5. Medical Faculty, Abadan University of Medical Sciences, Abadan, Iran
Introduction: The rise of antibiotic-resistant bacteria, particularly Klebsiella pneumoniae, poses a significant challenge to global health. This pathogen, a member of the Enterobacteriaceae family, is notorious for causing severe infections such as pneumonia, respiratory tract infections, and endocarditis, especially in immunocompromised individuals like those with AIDS. One of the key mechanisms behind its resistance is the production of the β-lactamase enzyme OXA-48, which hydrolyzes β-lactam antibiotics, including carbapenems, rendering them ineffective. Addressing this issue requires innovative approaches, such as identifying natural compounds that can inhibit OXA-48 and restore the efficacy of existing antibiotics.
Methods: This study focused on the essential oil of Mentha pulegium (oregano), a plant known for its antimicrobial properties. The primary objective was to evaluate the potential of oregano essential oil compounds to inhibit the OXA-48 enzyme through molecular docking and computational analysis. The crystallographic structure of OXA-48 in complex with imipenem (PDB ID: 7KH9) was obtained from the RCSB Protein Data Bank. The protein structure was prepared using Autodock Tools, where water molecules were removed, polar hydrogens were added, and the file was converted to PDBQT format for docking. Imipenem, the reference ligand, was also prepared similarly to validate the docking process. The essential oil of Mentha pulegium was extracted and analyzed using Gas Chromatography-Mass Spectroscopy (GC-MS), revealing 35 chemical compounds. These compounds were docked against the OXA-48 protein using AutoDock Vina to predict their binding affinities. Further analysis using SwissADME and PASS servers evaluated the pharmacokinetic and toxicity profiles of these compounds.
Results: The results identified three compounds—α-Muurolene (ΔG = -6.4 kcal/mol), Calamenene (ΔG = -6.1 kcal/mol), and Delta-Cadinene (ΔG = -6.0 kcal/mol)—with higher binding affinities than imipenem (ΔG = -5.3 kcal/mol). These compounds exhibited strong hydrophobic and van der Waals interactions with key amino acids in the OXA-48 active site, such as Thr209, Ser70, Leu247, Ser118, Tyr211, TRP105, Thr213, and Ile102, suggesting their potential as inhibitors. All three showed favorable absorption, distribution, and low toxicity, with no hepatotoxic or carcinogenic effects. Their ability to penetrate the blood-brain barrier and inhibit CYP enzymes was also noted, highlighting their potential as drug candidates.
Conclusion: In conclusion, this study demonstrates that Mentha pulegium essential oil contains compounds with significant inhibitory potential against OXA-48, offering a promising avenue for combating antibiotic resistance in Klebsiella pneumoniae. The findings underscore the value of natural products in drug discovery and pave the way for further experimental validation and clinical development of these compounds as adjunct therapies alongside existing antibiotics.