Targeting folate metabolism for therapeutic option: A bioinformatics approach.
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Date
2015-11
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Abstract
Lymphatic filariasis, commonly called elephantiasis, poses a burden of estimated level of 5.09 million disability adjusted life year. Limitations of its sole drug, diethylcarbamazine (DEC) drive exploration of effective filarial target. A few plant extracts having polyphenolic ingredients and some synthetic compounds possess potential dihydrofolate reductase (DHFR) inhibitory effect. Here, we postulated a plausible link between folates and polyphenolics based on their common precursor in shikimate metabolism. Considering its implication in structural resemblance based antagonism, we have attempted to validate parasitic DHFR protein as a target. The bioinformatics approach, in the absence of crystal structure of the proposed target, used to authenticate and for virtual docking with suitable tested compounds, showed remarkably lower thermodynamic parameters as opposed to the positive control. A comparative docking analysis between human and Brugia malayi DHFR also showed effective binding parameters with lower inhibition constants of these ligands with parasitic target, but not with human counterpart highlighting safety and efficacy. This study suggests that DHFR could be a valid drug target for lymphatic filariasis, and further reveal that bioinformatics may be an effective tool in reverse pharmacological approach for drug design.
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Keywords
Brugia malayi, Dihydrofolate reductase (DHFR), Drug design, Elephantiasis, Filariasis, Polyphenolics
Citation
Hande Sneha, Goswami Kalyan, Sharma Richa, Bhoj Priyanka, Jena Lingaraj, Reddy Maryada Venkata Rami. Targeting folate metabolism for therapeutic option: A bioinformatics approach. Indian Journal of Experimental Biology. 2015 Nov; 53(11): 762-766.