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• W3210557335 endingPage "6538" @default.
• W3210557335 startingPage "6538" @default.
• W3210557335 abstract "Inflammation plays an important role in different chronic diseases. Brominated indoles derived from the Australian marine mollusk Dicathais orbita (D. orbita) are of interest for their anti-inflammatory properties. This study evaluates the binding mechanism and potentiality of several brominated indoles (tyrindoxyl sulfate, tyrindoleninone, 6-bromoisatin, and 6,6'-dibromoindirubin) against inflammatory mediators cyclooxygenases-1/2 (COX-1/2) using molecular docking, followed by molecular dynamics simulation, along with physicochemical, drug-likeness, pharmacokinetic (pk), and toxicokinetic (tk) properties. Molecular docking identified that these indole compounds are anchored, with the main amino acid residues, positioned in the binding pocket of the COX-1/2, required for selective inhibition. Moreover, the molecular dynamics simulation based on root mean square deviation (RMSD), radius of gyration (Rg), solvent accessible surface area (SASA), and root mean square fluctuation (RMSF) analyses showed that these natural brominated molecules transit rapidly to a progressive constant configuration during binding with COX-1/2 and seem to accomplish a consistent dynamic behavior by maintaining conformational stability and compactness. The results were comparable to the Food and Drug Administration (FDA)-approved selective COX inhibitor, aspirin. Furthermore, the free energy of binding for the compounds assessed by molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA) confirmed the binding capacity of indoles towards COX-1/2, with suitable binding energy values except for the polar precursor tyrindoxyl sulfate (with COX-1). The physicochemical and drug-likeness analysis showed zero violations of Lipinski's rule, and the compounds are predicted to have excellent pharmacokinetic profiles. These indoles are projected to be non-mutagenic and free from hepatotoxicity, with no inhibition of human ether-a-go-go gene (hERG) I inhibitors, and the oral acute toxicity LD50 in rats is predicted to be similar or lower than aspirin. Overall, this work has identified a plausible mechanism for selective COX inhibition by natural marine indoles as potential therapeutic candidates for the mitigation of inflammation." @default.
• W3210557335 created "2021-11-08" @default.
• W3210557335 creator A5001388944 @default.
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• W3210557335 creator A5091851715 @default.
• W3210557335 date "2021-10-29" @default.
• W3210557335 modified "2023-10-17" @default.
• W3210557335 title "Mollusc-Derived Brominated Indoles for the Selective Inhibition of Cyclooxygenase: A Computational Expedition" @default.
• W3210557335 cites W1491051499 @default.
• W3210557335 cites W1561041814 @default.
• W3210557335 cites W1575925050 @default.
• W3210557335 cites W1586663904 @default.
• W3210557335 cites W1660326086 @default.
• W3210557335 cites W1674582945 @default.
• W3210557335 cites W1705576088 @default.
• W3210557335 cites W1946187642 @default.
• W3210557335 cites W1963514652 @default.
• W3210557335 cites W1964378600 @default.
• W3210557335 cites W1964470226 @default.
• W3210557335 cites W1968984443 @default.
• W3210557335 cites W1975580333 @default.
• W3210557335 cites W1976654542 @default.
• W3210557335 cites W1977791869 @default.
• W3210557335 cites W1980990431 @default.
• W3210557335 cites W1982046519 @default.
• W3210557335 cites W1984738107 @default.
• W3210557335 cites W1985588649 @default.
• W3210557335 cites W1990901377 @default.
• W3210557335 cites W1991392549 @default.
• W3210557335 cites W1991987072 @default.
• W3210557335 cites W1992623945 @default.
• W3210557335 cites W1997176513 @default.
• W3210557335 cites W1999401096 @default.
• W3210557335 cites W2002840016 @default.
• W3210557335 cites W2004159878 @default.
• W3210557335 cites W2009423060 @default.
• W3210557335 cites W2009867031 @default.
• W3210557335 cites W2010967782 @default.
• W3210557335 cites W2011885150 @default.
• W3210557335 cites W2012344270 @default.
• W3210557335 cites W2013166307 @default.
• W3210557335 cites W2013257331 @default.
• W3210557335 cites W2013777179 @default.
• W3210557335 cites W2017150228 @default.
• W3210557335 cites W2017581198 @default.
• W3210557335 cites W2018031414 @default.
• W3210557335 cites W2023302278 @default.
• W3210557335 cites W2024191422 @default.
• W3210557335 cites W2026091472 @default.
• W3210557335 cites W2029667189 @default.
• W3210557335 cites W2030850720 @default.
• W3210557335 cites W2033495141 @default.
• W3210557335 cites W2034294731 @default.
• W3210557335 cites W2037904566 @default.
• W3210557335 cites W2038781543 @default.
• W3210557335 cites W2039473230 @default.
• W3210557335 cites W2040092432 @default.
• W3210557335 cites W2042457093 @default.
• W3210557335 cites W2044844250 @default.
• W3210557335 cites W2046477056 @default.
• W3210557335 cites W2049520769 @default.
• W3210557335 cites W2049737988 @default.
• W3210557335 cites W2051446073 @default.
• W3210557335 cites W2054544606 @default.
• W3210557335 cites W2059781478 @default.
• W3210557335 cites W2060198845 @default.
• W3210557335 cites W2061228648 @default.
• W3210557335 cites W2061800084 @default.
• W3210557335 cites W2067468321 @default.
• W3210557335 cites W2071357022 @default.
• W3210557335 cites W2076498053 @default.
• W3210557335 cites W2076752483 @default.
• W3210557335 cites W2081162212 @default.
• W3210557335 cites W2081509920 @default.
• W3210557335 cites W2081521523 @default.
• W3210557335 cites W2082591684 @default.
• W3210557335 cites W2082647909 @default.
• W3210557335 cites W2083799886 @default.
• W3210557335 cites W2083946713 @default.
• W3210557335 cites W2085663480 @default.
• W3210557335 cites W2088905899 @default.
• W3210557335 cites W2089792802 @default.
• W3210557335 cites W2090632754 @default.
• W3210557335 cites W2098577478 @default.
• W3210557335 cites W2099099776 @default.
• W3210557335 cites W2099246483 @default.
• W3210557335 cites W2102479939 @default.
• W3210557335 cites W2111134372 @default.
• W3210557335 cites W2112855704 @default.
• W3210557335 cites W2115350007 @default.
• W3210557335 cites W2118233996 @default.
• W3210557335 cites W2118278569 @default.
• W3210557335 cites W2123274778 @default.
• W3210557335 cites W2126853519 @default.
• W3210557335 cites W2142195757 @default.

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