FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4367185791> ?p ?o ?g. }

• W4367185791 endingPage "59" @default.
• W4367185791 startingPage "49" @default.
• W4367185791 abstract "The enoyl-acyl carrier protein reductase (InhA) is one of the important key enzymes employed in mycolic acids biosynthesis pathway and an important component of mycobacterial cell walls. This enzyme has also been identified as major target of isoniazid drug, except that isoniazid needs to be activated first by the catalase peroxidase (KatG) protein to form the isonicotinoyl-NAD (INH-NAD) adduct that inhibits the action of InhA enzyme. However, this activation becomes more difficult and unreachable with the problem of mutation-related resistance caused mainly by acquired mutations in KatG and InhA protein. Our main interest in this study is to identify direct InhA inhibitors using computer-aided drug design.Computer-aided drug design was used to solve this problem by applying three different approaches including mutation impact modelling, virtual screening and 3D-pharmacophore search.A total of 15 mutations were collected from the literature, then a 3D model was generated for each of them and their impact was predicted. Of the 15 mutations, 10 were found to be deleterious and have a direct effect on flexibility, stability and SASA of the protein. In virtual screening, from 1,000 similar INH-NAD analogues obtained by the similarity search method, 823 compounds passed toxicity filter and drug likeness rules, which were then docked to the wild-type of InhA protein. Subsequently, 34 compounds with binding energy score better than that of INH-NAD were selected and docked against the 10 generated mutated models of InhA. Only three leads showed a lower binding affinity better than the reference. The 3D-pharmacophore model approach was used to identify the common features between those three compounds by generating a pharmacophoric map.The result of this study may pave the way to develop more potent mutant-specific inhibitors to overcome this resistance." @default.
• W4367185791 created "2023-04-28" @default.
• W4367185791 creator A5015088756 @default.
• W4367185791 creator A5061825805 @default.
• W4367185791 creator A5066956884 @default.
• W4367185791 creator A5077033367 @default.
• W4367185791 creator A5080975974 @default.
• W4367185791 creator A5085647009 @default.
• W4367185791 creator A5089930431 @default.
• W4367185791 date "2023-04-01" @default.
• W4367185791 modified "2023-09-30" @default.
• W4367185791 title "Facing Antitubercular Resistance: Identification of Potential Direct Inhibitors Targeting InhA Enzyme and Generation of 3D-pharmacophore Model by in silico Approach" @default.
• W4367185791 cites W1526205344 @default.
• W4367185791 cites W1967436230 @default.
• W4367185791 cites W1971174290 @default.
• W4367185791 cites W1981769964 @default.
• W4367185791 cites W1982542062 @default.
• W4367185791 cites W1990791344 @default.
• W4367185791 cites W1995193856 @default.
• W4367185791 cites W1998078072 @default.
• W4367185791 cites W2027340405 @default.
• W4367185791 cites W2051555720 @default.
• W4367185791 cites W2067565253 @default.
• W4367185791 cites W2073691834 @default.
• W4367185791 cites W2075000963 @default.
• W4367185791 cites W2087001808 @default.
• W4367185791 cites W2093712250 @default.
• W4367185791 cites W2105649494 @default.
• W4367185791 cites W2105668062 @default.
• W4367185791 cites W2108628979 @default.
• W4367185791 cites W2111326065 @default.
• W4367185791 cites W2113461878 @default.
• W4367185791 cites W2117610468 @default.
• W4367185791 cites W2126609323 @default.
• W4367185791 cites W2128034051 @default.
• W4367185791 cites W2131523466 @default.
• W4367185791 cites W2132629607 @default.
• W4367185791 cites W2134334215 @default.
• W4367185791 cites W2134967712 @default.
• W4367185791 cites W2139106269 @default.
• W4367185791 cites W2149580316 @default.
• W4367185791 cites W2160175061 @default.
• W4367185791 cites W2166757164 @default.
• W4367185791 cites W2169678694 @default.
• W4367185791 cites W2170154548 @default.
• W4367185791 cites W2265245360 @default.
• W4367185791 cites W2414200852 @default.
• W4367185791 cites W2568617656 @default.
• W4367185791 cites W2620998958 @default.
• W4367185791 cites W2801088198 @default.
• W4367185791 cites W2801491392 @default.
• W4367185791 cites W2811374524 @default.
• W4367185791 cites W2972457079 @default.
• W4367185791 cites W3016722909 @default.
• W4367185791 cites W3022734398 @default.
• W4367185791 cites W4207070825 @default.
• W4367185791 cites W4226086528 @default.
• W4367185791 cites W4289225536 @default.
• W4367185791 cites W4298142888 @default.
• W4367185791 doi "https://doi.org/10.2147/aabc.s394535" @default.
• W4367185791 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37143606" @default.
• W4367185791 hasPublicationYear "2023" @default.
• W4367185791 type Work @default.
• W4367185791 citedByCount "0" @default.
• W4367185791 crossrefType "journal-article" @default.
• W4367185791 hasAuthorship W4367185791A5015088756 @default.
• W4367185791 hasAuthorship W4367185791A5061825805 @default.
• W4367185791 hasAuthorship W4367185791A5066956884 @default.
• W4367185791 hasAuthorship W4367185791A5077033367 @default.
• W4367185791 hasAuthorship W4367185791A5080975974 @default.
• W4367185791 hasAuthorship W4367185791A5085647009 @default.
• W4367185791 hasAuthorship W4367185791A5089930431 @default.
• W4367185791 hasBestOaLocation W43671857911 @default.
• W4367185791 hasConcept C103697762 @default.
• W4367185791 hasConcept C104317684 @default.
• W4367185791 hasConcept C142724271 @default.
• W4367185791 hasConcept C181199279 @default.
• W4367185791 hasConcept C185592680 @default.
• W4367185791 hasConcept C2775905019 @default.
• W4367185791 hasConcept C2776967927 @default.
• W4367185791 hasConcept C2780687663 @default.
• W4367185791 hasConcept C2781069245 @default.
• W4367185791 hasConcept C55493867 @default.
• W4367185791 hasConcept C56173144 @default.
• W4367185791 hasConcept C70721500 @default.
• W4367185791 hasConcept C71924100 @default.
• W4367185791 hasConcept C75520062 @default.
• W4367185791 hasConcept C86803240 @default.
• W4367185791 hasConceptScore W4367185791C103697762 @default.
• W4367185791 hasConceptScore W4367185791C104317684 @default.
• W4367185791 hasConceptScore W4367185791C142724271 @default.
• W4367185791 hasConceptScore W4367185791C181199279 @default.
• W4367185791 hasConceptScore W4367185791C185592680 @default.
• W4367185791 hasConceptScore W4367185791C2775905019 @default.
• W4367185791 hasConceptScore W4367185791C2776967927 @default.
• W4367185791 hasConceptScore W4367185791C2780687663 @default.
• W4367185791 hasConceptScore W4367185791C2781069245 @default.
• W4367185791 hasConceptScore W4367185791C55493867 @default.

• next