Synthesis and antibacterial potential of novel thymol derivatives against methicillin-resistant Staphylococcus aureus and P. aeruginosa pathogenic bacteria.
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Abstract
The increasing threat of antibiotic resistance has created an urgent need for new antibacterial agents, particularly plant-based natural compounds and their derivatives. Thymol, a natural monoterpenoid phenolic compound derived from Monarda citriodora, is known for its aromatic and therapeutic properties, including antibacterial activity. This study focuses on synthesizing dihydropyrimidinone and dihydropyridine derivatives of thymol and exploring their antibacterial properties. The synthesized compounds were tested for their in vitro antibacterial potential against pathogenic microorganisms, specifically Pseudomonas aeruginosa (Gram-negative) and methicillin-resistant Staphylococcus aureus (MRSA) (Gram-positive). Among the synthesized derivatives, compound 3i (ethyl 4-(4-hydroxy-5-isopropyl-2-methylphenyl)-2-imino-6-methyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate) exhibited the most promising antibacterial activity, with minimum inhibitory concentration (MIC) values of 12.5 µM against P. aeruginosa and 50.0 µM against MRSA. Additionally, compound 3i demonstrated a synergistic effect when combined with vancomycin, enhancing its antibacterial efficacy. The optimum fractional inhibitory concentration index (FICI) observed was 0.10 and 0.5 for MRSA and P. aeruginosa, respectively, in combination with vancomycin. In silico analysis of the physiochemical properties of 3i indicated compliance with all drug-likeness rules. Furthermore, molecular docking studies revealed that compound 3i has a stronger binding affinity to the target protein than thymol, providing valuable insights into its potential mechanism of action.
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Frontiers in Chemistry is a high visiblity and quality journal, publishing rigorously peer-reviewed research across the chemical sciences. Field Chief Editor Steve Suib at the University of Connecticut is supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to academics, industry leaders and the public worldwide.
Chemistry is a branch of science that is linked to all other main fields of research. The omnipresence of Chemistry is apparent in our everyday lives from the electronic devices that we all use to communicate, to foods we eat, to our health and well-being, to the different forms of energy that we use. While there are many subtopics and specialties of Chemistry, the fundamental link in all these areas is how atoms, ions, and molecules come together and come apart in what some have come to call the “dance of life”.
All specialty sections of Frontiers in Chemistry are open-access with the goal of publishing outstanding research publications, review articles, commentaries, and ideas about various aspects of Chemistry. The past forms of publication often have specific subdisciplines, most commonly of analytical, inorganic, organic and physical chemistries, but these days those lines and boxes are quite blurry and the silos of those disciplines appear to be eroding. Chemistry is important to both fundamental and applied areas of research and manufacturing, and indeed the outlines of academic versus industrial research are also often artificial. Collaborative research across all specialty areas of Chemistry is highly encouraged and supported as we move forward. These are exciting times and the field of Chemistry is an important and significant contributor to our collective knowledge.
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