Matches in SemOpenAlex for { <https://semopenalex.org/work/W4321328497> ?p ?o ?g. }
- W4321328497 abstract "Type IA topoisomerases maintain DNA topology by cleaving ssDNA and relaxing negative supercoils. The inhibition of its activity in bacteria prevents the relaxation of negative supercoils, which in turn impedes DNA metabolic processes leading to cell death. Using this hypothesis, two bisbenzimidazoles, PPEF and BPVF are synthesized, selectively inhibiting bacterial TopoIA and TopoIII. PPEF stabilizes the topoisomerase and topoisomerase-ssDNA complex, acts as an interfacial inhibitor. PPEF display high efficacy against ~455 multi-drug resistant gram positive and negative bacteria. To understand molecular mechanism of inhibition of TopoIA and PPEF, accelerated MD simulation is carried out, and results suggested that PPEF binds, stabilizes the closed conformation of TopoIA with -6Kcal/mol binding energy and destabilizes the binding of ssDNA. The TopoIA gate dynamics model can be used as a tool to screen TopoIA inhibitors as therapeutic candidates. PPEF and BPVF cause cellular filamentation and DNA fragmentation leading to bacterial cell death. PPEF and BPVF show potent efficacy against systemic and neutropenic mouse models harboring E. coli, VRSA, and MRSA infection without cellular toxicity." @default.
- W4321328497 created "2023-02-19" @default.
- W4321328497 creator A5000184114 @default.
- W4321328497 creator A5003136627 @default.
- W4321328497 creator A5008398215 @default.
- W4321328497 creator A5016074569 @default.
- W4321328497 creator A5036804197 @default.
- W4321328497 creator A5051194562 @default.
- W4321328497 creator A5055493700 @default.
- W4321328497 creator A5056679615 @default.
- W4321328497 creator A5065435920 @default.
- W4321328497 creator A5082462719 @default.
- W4321328497 date "2023-02-18" @default.
- W4321328497 modified "2023-09-26" @default.
- W4321328497 title "Unraveling topoisomerase IA gate dynamics in presence of PPEF and its preclinical evaluation against multidrug-resistant pathogens" @default.
- W4321328497 cites W1596505006 @default.
- W4321328497 cites W1607931568 @default.
- W4321328497 cites W1817548902 @default.
- W4321328497 cites W1838060106 @default.
- W4321328497 cites W1888462442 @default.
- W4321328497 cites W1970179483 @default.
- W4321328497 cites W1976499671 @default.
- W4321328497 cites W1981267913 @default.
- W4321328497 cites W1994490060 @default.
- W4321328497 cites W2001467626 @default.
- W4321328497 cites W2007302027 @default.
- W4321328497 cites W2012251902 @default.
- W4321328497 cites W2014403384 @default.
- W4321328497 cites W2021364260 @default.
- W4321328497 cites W2032054300 @default.
- W4321328497 cites W2032582880 @default.
- W4321328497 cites W2033172181 @default.
- W4321328497 cites W2035266068 @default.
- W4321328497 cites W2041638382 @default.
- W4321328497 cites W2046256887 @default.
- W4321328497 cites W2050255140 @default.
- W4321328497 cites W2054913898 @default.
- W4321328497 cites W2067174909 @default.
- W4321328497 cites W2076233570 @default.
- W4321328497 cites W2081693079 @default.
- W4321328497 cites W2097697790 @default.
- W4321328497 cites W2128572087 @default.
- W4321328497 cites W2129645109 @default.
- W4321328497 cites W2131717798 @default.
- W4321328497 cites W2138826821 @default.
- W4321328497 cites W2139861245 @default.
- W4321328497 cites W2144288821 @default.
- W4321328497 cites W2146411229 @default.
- W4321328497 cites W2146639370 @default.
- W4321328497 cites W2147093387 @default.
- W4321328497 cites W2147993766 @default.
- W4321328497 cites W2147997050 @default.
- W4321328497 cites W2153983456 @default.
- W4321328497 cites W2159496849 @default.
- W4321328497 cites W2167038712 @default.
- W4321328497 cites W2168765024 @default.
- W4321328497 cites W2169119507 @default.
- W4321328497 cites W2320986103 @default.
- W4321328497 cites W2325595757 @default.
- W4321328497 cites W2344264715 @default.
- W4321328497 cites W2404280981 @default.
- W4321328497 cites W2433523887 @default.
- W4321328497 cites W2518684392 @default.
- W4321328497 cites W2597291548 @default.
- W4321328497 cites W2732293141 @default.
- W4321328497 cites W2779019546 @default.
- W4321328497 cites W2794190210 @default.
- W4321328497 cites W2801156774 @default.
- W4321328497 cites W2807183240 @default.
- W4321328497 cites W2905662251 @default.
- W4321328497 cites W2947358910 @default.
- W4321328497 cites W2951759617 @default.
- W4321328497 cites W2956579761 @default.
- W4321328497 cites W2998807596 @default.
- W4321328497 cites W3005694025 @default.
- W4321328497 cites W3009907822 @default.
- W4321328497 cites W3092054218 @default.
- W4321328497 cites W4236530034 @default.
- W4321328497 doi "https://doi.org/10.1038/s42003-023-04412-1" @default.
- W4321328497 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36807602" @default.
- W4321328497 hasPublicationYear "2023" @default.
- W4321328497 type Work @default.
- W4321328497 citedByCount "0" @default.
- W4321328497 crossrefType "journal-article" @default.
- W4321328497 hasAuthorship W4321328497A5000184114 @default.
- W4321328497 hasAuthorship W4321328497A5003136627 @default.
- W4321328497 hasAuthorship W4321328497A5008398215 @default.
- W4321328497 hasAuthorship W4321328497A5016074569 @default.
- W4321328497 hasAuthorship W4321328497A5036804197 @default.
- W4321328497 hasAuthorship W4321328497A5051194562 @default.
- W4321328497 hasAuthorship W4321328497A5055493700 @default.
- W4321328497 hasAuthorship W4321328497A5056679615 @default.
- W4321328497 hasAuthorship W4321328497A5065435920 @default.
- W4321328497 hasAuthorship W4321328497A5082462719 @default.
- W4321328497 hasBestOaLocation W43213284971 @default.
- W4321328497 hasConcept C120665830 @default.
- W4321328497 hasConcept C121332964 @default.
- W4321328497 hasConcept C12554922 @default.
- W4321328497 hasConcept C143425029 @default.
- W4321328497 hasConcept C147897179 @default.