Matches in SemOpenAlex for { <https://semopenalex.org/work/W2913503312> ?p ?o ?g. }
- W2913503312 endingPage "582" @default.
- W2913503312 startingPage "562" @default.
- W2913503312 abstract "In search for effective multi-targeting drug ligands (MTDLs) to address low-grade inflammatory changes of metabolic disorders, we rationally designed some novel glitazones-like compounds. This was achieved by incorporating prominent pharmacophoric motifs from previously reported COX-2, 15-LOX and PPARγ ligands. Challenging our design with pre-synthetic docking experiments on PPARγ showed encouraging results. In vitro tests have identified 4 compounds as simultaneous partial PPARγ agonist, potent COX-2 antagonist (nanomolar IC50 values) and moderate 15-LOX inhibitor (micromolar IC50 values). We envisioned such outcome as a prototypical balanced modulation of the 3 inflammatory targets. In vitro glucose uptake assay defined six compounds as insulin-sensitive and the other two as insulin-independent glucose uptake enhancers. Also, they were able to induce PPARγ nuclear translocation in immunohistochemical analysis. Their anti-inflammatory potential has been translated to effective inhibition of monocyte to macrophage differentiation, suppression of LPS-induced inflammatory cytokine production in macrophages, as well as significant in vivo anti-inflammatory activity. Ligand co-crystallized PPARγ X-ray of one of MTDLs has identified new clues that could serve as structural basis for its partial agonism. Docking of the most active compounds into COX-2 and 15-LOX active sites, pinpointed favorable binding patterns, similar to those of the co-crystallized ligands. Finally, in silico assessment of pharmacokinetics, physicochemical properties, drug-likeness and ligand efficiency indices was performed. Hence, we anticipate that the prominent biological profile of such series will rationalize relevant anti-inflammatory drug development endeavors." @default.
- W2913503312 created "2019-02-21" @default.
- W2913503312 creator A5002404376 @default.
- W2913503312 creator A5002629135 @default.
- W2913503312 creator A5010299845 @default.
- W2913503312 creator A5011180484 @default.
- W2913503312 creator A5017576916 @default.
- W2913503312 creator A5049287944 @default.
- W2913503312 creator A5049415568 @default.
- W2913503312 creator A5049764379 @default.
- W2913503312 creator A5063368213 @default.
- W2913503312 creator A5063952642 @default.
- W2913503312 creator A5066957693 @default.
- W2913503312 creator A5068522704 @default.
- W2913503312 creator A5069680451 @default.
- W2913503312 creator A5090808178 @default.
- W2913503312 date "2019-04-01" @default.
- W2913503312 modified "2023-10-15" @default.
- W2913503312 title "Shooting three inflammatory targets with a single bullet: Novel multi-targeting anti-inflammatory glitazones" @default.
- W2913503312 cites W1066986691 @default.
- W2913503312 cites W1135792216 @default.
- W2913503312 cites W1520589846 @default.
- W2913503312 cites W1535583521 @default.
- W2913503312 cites W1756692753 @default.
- W2913503312 cites W1806538103 @default.
- W2913503312 cites W1861386078 @default.
- W2913503312 cites W1878686232 @default.
- W2913503312 cites W1923917571 @default.
- W2913503312 cites W1961611438 @default.
- W2913503312 cites W1967105675 @default.
- W2913503312 cites W1971981814 @default.
- W2913503312 cites W1972291024 @default.
- W2913503312 cites W1979600197 @default.
- W2913503312 cites W1981348906 @default.
- W2913503312 cites W1981561631 @default.
- W2913503312 cites W1982766494 @default.
- W2913503312 cites W1985502949 @default.
- W2913503312 cites W1988437166 @default.
- W2913503312 cites W1990106417 @default.
- W2913503312 cites W1992595909 @default.
- W2913503312 cites W2000406857 @default.
- W2913503312 cites W2000709344 @default.
- W2913503312 cites W2001881588 @default.
- W2913503312 cites W2006351227 @default.
- W2913503312 cites W2007187686 @default.
- W2913503312 cites W2009170266 @default.
- W2913503312 cites W2010993726 @default.
- W2913503312 cites W2015097584 @default.
- W2913503312 cites W2020443182 @default.
- W2913503312 cites W2031565266 @default.
- W2913503312 cites W2037166744 @default.
- W2913503312 cites W2039738410 @default.
- W2913503312 cites W2040380614 @default.
- W2913503312 cites W2045962653 @default.
- W2913503312 cites W2048830136 @default.
- W2913503312 cites W2050456292 @default.
- W2913503312 cites W2052891613 @default.
- W2913503312 cites W2059497015 @default.
- W2913503312 cites W2062014588 @default.
- W2913503312 cites W2062753270 @default.
- W2913503312 cites W2062756785 @default.
- W2913503312 cites W2068100830 @default.
- W2913503312 cites W2068630163 @default.
- W2913503312 cites W2071156482 @default.
- W2913503312 cites W2075879675 @default.
- W2913503312 cites W2076891180 @default.
- W2913503312 cites W2079331631 @default.
- W2913503312 cites W2089090637 @default.
- W2913503312 cites W2093839463 @default.
- W2913503312 cites W2097420030 @default.
- W2913503312 cites W2098846895 @default.
- W2913503312 cites W2103299776 @default.
- W2913503312 cites W2106290432 @default.
- W2913503312 cites W2108777528 @default.
- W2913503312 cites W2111727066 @default.
- W2913503312 cites W2113023385 @default.
- W2913503312 cites W2113934014 @default.
- W2913503312 cites W2124026197 @default.
- W2913503312 cites W2126894693 @default.
- W2913503312 cites W2129319023 @default.
- W2913503312 cites W2134201060 @default.
- W2913503312 cites W2135186594 @default.
- W2913503312 cites W2141528038 @default.
- W2913503312 cites W2146624819 @default.
- W2913503312 cites W2154197653 @default.
- W2913503312 cites W2168378234 @default.
- W2913503312 cites W2169678694 @default.
- W2913503312 cites W2176372816 @default.
- W2913503312 cites W2179359515 @default.
- W2913503312 cites W2206437677 @default.
- W2913503312 cites W2217914754 @default.
- W2913503312 cites W2255320251 @default.
- W2913503312 cites W2259013233 @default.
- W2913503312 cites W2314990578 @default.
- W2913503312 cites W2326184045 @default.
- W2913503312 cites W2336051806 @default.
- W2913503312 cites W2395184176 @default.
- W2913503312 cites W2408522200 @default.