caa a22 4500 605511195 CHVBK 20210128100649.0 cr unu---uuuuu 210128e20150901xx s 000 0 eng 10.1007/s00894-015-2785-z doi (NATIONALLICENCE)springer-10.1007/s00894-015-2785-z Computational evaluation of phytocompounds for combating drug resistant tuberculosis by multi-targeted therapy [Elektronische Daten] [Sudharsana Sundarrajan, Sajitha Lulu, Mohanapriya Arumugam] The cell wall of Mycobacterium tuberculosis interacts with the host counterpart during the pathogenesis of tuberculosis. L-rhamnosyl (L-Rha) residue, a linker connects the arabinogalactan and peptidoglycan moieties in the bacterial cell wall. The biosynthesis of L-rhamnose utilizes four successive enzymes RmlA, RmlB, RmlC and RmlD. Neither rhamnose nor the genes responsible for its synthesis are observed in humans. Thus, drugs inhibiting enzymes of this pathway are unlikely to interfere with metabolic pathways in humans. The adverse drug effects of first and second line drugs along with the development of multi-drug resistance tuberculosis have stimulated the research in search of new therapeutic drugs. Thus, it is attractive to hypothesize that inhibition of the biosynthesis of L-Rha would be lethal to the mycobacteria. Nature provides innumerable secondary metabolites with novel structural architectures with reported activity against M.tuberculosis. Combination of structure based virtual screening with physicochemical and pharmacokinetic studies against rhamnose pathway enzymes identified potential leads. The crucial screening studies recognized four phytocompounds butein, diospyrin, indicanine, and rumexneposide A with good binding affinity towards the rhamnose pathway proteins. Furthermore, the high throughput screening methods recognized butein, a secondary metabolite from Butea monosperma with strong anti-tubercular bioactive spectrum. Butein displayed promising anti-mycobacterial activity which is validated by Microplate alamar blue assay (MABA). The focus on novel agents like these phytocompounds which exhibit preference toward the successive enzymes of a single pathway can prevent the development of bacterial resistance. Springer-Verlag Berlin Heidelberg, 2015 Mycobacterium nationallicence Phytocompounds nationallicence Rhamnose bio-synthesis nationallicence Virtual screening nationallicence Sundarrajan Sudharsana Bioinformatics Division, School of Biosciences and Technology, Vellore Institute of Technology University, 632014, Vellore, Tamil Nadu, India aut Lulu Sajitha Bioinformatics Division, School of Biosciences and Technology, Vellore Institute of Technology University, 632014, Vellore, Tamil Nadu, India aut Arumugam Mohanapriya Bioinformatics Division, School of Biosciences and Technology, Vellore Institute of Technology University, 632014, Vellore, Tamil Nadu, India aut Journal of Molecular Modeling Springer Berlin Heidelberg 21/9(2015-09-01), 1-16 1610-2940 21:9<1 2015 21 894 https://doi.org/10.1007/s00894-015-2785-z text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00894-015-2785-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Sundarrajan Sudharsana Bioinformatics Division, School of Biosciences and Technology, Vellore Institute of Technology University, 632014, Vellore, Tamil Nadu, India aut NATIONALLICENCE 700 1- Lulu Sajitha Bioinformatics Division, School of Biosciences and Technology, Vellore Institute of Technology University, 632014, Vellore, Tamil Nadu, India aut NATIONALLICENCE 700 1- Arumugam Mohanapriya Bioinformatics Division, School of Biosciences and Technology, Vellore Institute of Technology University, 632014, Vellore, Tamil Nadu, India aut NATIONALLICENCE 773 0- Journal of Molecular Modeling Springer Berlin Heidelberg 21/9(2015-09-01), 1-16 1610-2940 21:9<1 2015 21 894