Publication: Halogenated trimethoprim derivatives as multidrug-resistant Staphylococcus aureus therapeutics
Issued Date
2018-10-15
Resource Type
ISSN
14643391
09680896
09680896
Other identifier(s)
2-s2.0-85047094628
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Bioorganic and Medicinal Chemistry. Vol.26, No.19 (2018), 5343-5348
Suggested Citation
Napon Nilchan, Wanida Phetsang, Taechin Nowwarat, Soraya Chaturongakul, Chutima Jiarpinitnun Halogenated trimethoprim derivatives as multidrug-resistant Staphylococcus aureus therapeutics. Bioorganic and Medicinal Chemistry. Vol.26, No.19 (2018), 5343-5348. doi:10.1016/j.bmc.2018.05.019 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/45028
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Halogenated trimethoprim derivatives as multidrug-resistant Staphylococcus aureus therapeutics
Other Contributor(s)
Abstract
© 2018 Elsevier Ltd Incorporation of halogen atoms to drug molecule has been shown to improve its properties such as enhanced in membrane permeability and increased hydrophobic interactions to its target. To investigate the effect of halogen substitutions on the antibacterial activity of trimethoprim (TMP), we synthesized a series of halogen substituted TMP and tested for their antibacterial activities against global predominant methicillin resistant Staphylococcus aureus (MRSA) strains. Structure-activity relationship analysis suggested a trend in potency that correlated with the ability of the halogen atom to facilitate in hydrophobic interaction to saDHFR. The most potent derivative, iodinated trimethoprim (TMP-I), inhibited pathogenic bacterial growth with MIC as low as 1.25 μg/mL while the clinically used TMP derivative, diaveridine, showed resistance. Similar to TMP, synergistic studies indicated that TMP-I functioned synergistically with sulfamethoxazole. The simplicity in the synthesis from an inexpensive starting material, vanillin, highlighted the potential of TMP-I as antibacterial agent for MRSA infections.