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|Title:||Hybrid-drug design targeting pseudomonas aeruginosa DHPS and DHFR||Authors:||Jayaraman, Premkumar
Daniel, Lim Chu Siang
Siddiqi, Mohammad Imran
Dhillon, Sarinder Kaur
Sakharkar, Kishore R.
Sakharkar, Meena K.
|Keywords:||DRNTU::Science::Biological sciences||Issue Date:||2013||Source:||Jayaraman, P., Sakharkar, K. R., Daniel, L. C. S., Siddiqi, M. I., Dhillon, S. K., et al. (2013). Hybrid-drug design targeting pseudomonas aeruginosa DHPS and DHFR. Frontiers in bioscience, 5, 864-882.||Series/Report no.:||Frontiers in bioscience||Abstract:||In this study, we successfully present the dual-target design hypothesis to inhibit both dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR) enzymes using a novel scheme that integrates our previous antibiotic-phytochemical interaction data, fragment combination and knowledge-based methods. Both the enzymes are well established antibacterial targets from folate biosynthesis pathway and their synergistic modulation by a single hybrid entity may have profound therapeutic benefits. Evaluation of the designed hybrid compounds based on their physico-chemical properties has indicated them as promising drug candidates with drug-like pharmacotherapeutic profiles. In addition, the stereo-electronic properties such as HOMO, LUMO and MEP maps calculated by quantum chemical methods gave a good correlation with the common pharmacophoric features required for dual-site interactions. Furthermore, docking and dynamics simulation studies reveal that the designed hybrid compounds have favorable binding affinity and stability in both pterin-binding site of DHPS and folate-binding site of DHFR by forming strong hydrogen bonds and hydrophobic interactions with key active-site residues. Looking forward this study could serve as a prospective lead in the process of new natural-product based hybrid-drugs development.||URI:||https://hdl.handle.net/10356/84863
|DOI:||10.2741/E666||Rights:||© 2013 Frontiers in Bioscience.||Fulltext Permission:||none||Fulltext Availability:||No Fulltext|
|Appears in Collections:||SCBE Journal Articles|
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