Please use this identifier to cite or link to this item: https://doi.org/10.3109/10611861003801867
Title: Insights into antifolate activity of phytochemicals against Pseudomonas aeruginosa
Authors: Jayaraman, P.
Sakharkar, K.R.
Sing, L.C.
Chow, V.T.K. 
Sakharkar, M.K.
Keywords: drug resistance
molecular modeling
phytochemicals
Synergy
Issue Date: Apr-2011
Source: Jayaraman, P., Sakharkar, K.R., Sing, L.C., Chow, V.T.K., Sakharkar, M.K. (2011-04). Insights into antifolate activity of phytochemicals against Pseudomonas aeruginosa. Journal of Drug Targeting 19 (3) : 179-188. ScholarBank@NUS Repository. https://doi.org/10.3109/10611861003801867
Abstract: Pseudomonas aeruginosa is an opportunistic drug resistant pathogen. Drug interaction studies for phytochemicals (protocatechuic acid (PA), gallic acid (GA), quercetin (QUER), and myricetin (MYR)) in combination with antifolates (sulfamethoxazole (SMX) and trimethoprim (TMP)) are presented. Our results show that the combinations of SMX and phytochemicals are synergistic, whereas TMP in combination with phytochemicals results in additive mode of interaction. Molecular docking of phytochemicals in the active site of modeled P. aeruginosa dihydrofolate reductase (DHFR), an important enzyme in the folic acid biosynthesis pathway, shows that the phytochemicals QUER and MYR dock in the active site of P. aeruginosa DHFR with promoted binding at the NADP site, PA, and GA dock in the active site of P. aeruginosa DHFR with promoted binding at the folate binding site. Possible mode of action of these phytochemicals as anti-DHFR compounds in this bacterium is suggested. Taken together, the above findings provide novel insights to mode of interactions of these phytochemicals with antibiotics and may have significance as prospective leads in the development of antipseudomonal drug developments. © 2011 Informa UK, Ltd.
Source Title: Journal of Drug Targeting
URI: http://scholarbank.nus.edu.sg/handle/10635/126734
ISSN: 1061186X
DOI: 10.3109/10611861003801867
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