Wang resin catalyzed green synthesis of 1,8-dioxo-octahydroxanthene derivatives and their in silico/in vitro evaluation against SIRT1

Discovery of Novel N-Acylhydrazone Derivatives as Potent Inhibitors of Sirtuin-1

“…Due to the well-characterized structure, the catalytic domain of SIRT1 has been used as a target receptor for in silico screening of binding parameters of SIRT1 modulators. 44 45 46 47 48 49 50 , 58 , 61 62 63…”

“…25 Over the past years, different SIRT inhibitors have been found among various classes of compounds. 7,[26][27][28][29][30][31][32] Downregulating activity towards HDACs class III was identified in 2-anilinobenzamides (nicotinamide analogues), 33 some acetyl lysine mimics, 26 azomethines based on 2-hydroxy-1naphthaldehyde (sirtinol, JGB1714 and others analogues), 34,35 thioureas (cambinol, tenovin-6), 36,37 and thiobarbituric acid 5-ylidene derivatives, 38 bis(indolyl)maleinimides, 34 5-benzylidene-2-phenyl-1,3-dioxane-4,6-diones 39 and indole derivatives, 40,41 naphtho[2,1-b]pyrane-3ones (splitomicin and analogues), 42 thieno[3,2-d]pyrimidine-6-carboxamides, 43 2-substituted nicotinic acid ethyl esters, 44 dihydro-1,4-benzoxazine carboxamides, 45 1,5-dihydro-1H-pyrano[2,3-d]pyrimidine-2,4(3H)-diones, 46 dihydropyrano[2,3-c]pyrazole, 47 2-arylamino-3-cyanopyridines, 48 3-heteroarylmethylene isoindolin-1-ones, 49 1,8-dioxo-octahydroxanthenes, 50 highly ionized naphthylurea suramin, 51 and various substances from natural sources (amurensin G) 52 or modified natural products such as steroids. 35 Most of these compounds have been evaluated using enzymatic and cell-based assays.…”

“…Due to the well-characterized structure, the catalytic domain of SIRT1 has been used as a target receptor for in silico screening of binding parameters of SIRT1 modulators. [44][45][46][47][48][49][50]58,[61][62][63] To test whether our molecular docking approach is able to reproduce properly the correct binding mode of the cocrystallized inhibitor Ex527, we first re-docked it against the corresponding crystal structure of SIRT1 (PDB 4I5I). 58 It has been suggested that the presence of the co-factor NAD + was essential for the activity of the SIRT1 enzyme 45 so it was maintained in the binding site for the docking study.…”

Recent Advances in the Discovery of SIRT1/2 Inhibitors via Computational Methods: A Perspective

“…More recently (2022), a small-scale VS of a series of 1,8-dioxo-octahydroxanthene derivatives was performed by Manikanttha et al on the SIRT1 catalytic domain [76]. This class of derivatives was reported to be promising in cancer therapy by tests on several cell lines, and similar compounds were already reported as potentially active on sirtuins [86][87][88].…”

“…Tripeptide linked to heterocyclic nuclei [117] Furopyridine derivatives [118] Indole compounds (strictly related to EX-527) [119] Benzylidene-dioxane compounds [120] Pyridine derivatives [121,122] Tryptophan conjugates [77] Pyrano [2,3-d ]pyrimidinone derivatives [123] Variable five-membered ring derivatives [81] Thienopyrimidone derivatives [74] 1,8-dioxo-octahydroxanthene derivatives [76]…”