Design, synthesis and anti-diabetic activity of some novel xanthone derivatives targeting α-glucosidase

Abstract

<p>Twenty eight xanthone derivatives were designed and docked into the N-terminal catalytic domain of maltase-glucoamylase (ntMGAM) by considering Miglitol as standard drug. Most of the molecules showed excellent docking scores and docking interaction as compared to the binding cavity of the standard molecule. The five best scoring ligands were synthesized and characterized by a number of analytical and spectroscopic techniques. The molecules were screened for the <em>in vivo</em> antidiabetic activity in streptozotocin (STZ) induced diabetic animal model in Wistar rats. Compound P4 showed the most prominent inhibition among others. The synthesized compounds reported significant (p< 0.01) effect of lowering glucose levels in the blood compared to miglitol as a standard α-glucosidase inhibitor.</p><p><strong>Video clip</strong></p><p>Induction of diabetes: </p>

Recent advances in the synthesis of xanthones and azaxanthones

“…9,10 Substitution of phosphorus oxychloride-zinc chloride by phosphorus pentoxide-methanesulfonic acid (Eaton's reagent) as an acylation catalyst generally led to better results. 18,19,23,24,33,35,40,50,54,59,63,70,[106][107][108][109][110][111][112][113][114][115][116][117][118][119][120][121] Since both of these methodologies had previously been extensively reviewed, 9,10 they will not be discussed herein.…”

“…89,[206][207][208][209][210][211][212][213][214][215][216][217][218] 7 Diversification on the xanthone core Hydroxyl groups are undoubtedly one of the most versatile functional groups when it comes to structural modifications (Scheme 26). A myriad of examples have been described in the literature, including the reaction with alkyl halides for the transformation into alkoxy, 43,59,69,[219][220][221][222][223] haloalkoxy, 18,51,69,99,224 methyl alkyl-or aryl-piperazine moieties, 225 epoxypropanoxy 65,103,[220][221][222] oxirane 221 , oxypropanolamines, 103 benzenesulfonamides, 226 and propargyloxy. 45,52,54,63,106,118,173,227,228 When reacted with other compounds that are not alkyl halides, several other functional-Scheme 25 Other methodologies for the synthesis of xanthones.…”

“…In the last decade, both natural and synthetic xanthones have been reported with diverse biological and pharmacological properties, 5,6,8,16 including antibacterial, 8,17-27 antifungal, 8,17,20,21,[28][29][30] antiviral, 31 antioxidant, [32][33][34][35][36][37] antiobesity, 38 anti-inflammatory, 5,17,[39][40][41] anticoagulant, 42 and antitumour. 36,[43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58] Particularly, some xanthones' molecular targets have been disclosed, including clinically important enzymes such as α-glucosidase, [59][60][61][62][63] topoisomerase, 64,…”

Antidiabetic and antiulcerative potential of Garcinia lanceifolia Roxb. bark

“…Pharmacological interventions are available for both the problems but being as synthetic chemicals, they target some other functions causing unwanted toxicities. Antidiabetic agents like biguanides, sulfonylureas, αglucosidase inhibitors [13], PPAR-γ agonists, SGLT-2 antagonist, and DPP-IV inhibitors, [6,14,15] are controlling the pandemic condition either in single mode or in combination but cardiac and hepatic tissues affected in most of the case. For treating peptic ulcer proton pump inhibitors (PPI), H 2 receptor antagonists, antimuscarinics, sucralfate, and bismuth are employed but they are also having additive effects [16].…”

Peroxisome Proliferator-Activated Receptor-Gamma, an Emerging Potential Target to Combat Metabolic Disorder

“…In major cases, the treatment proceeds emphasizing diabetes and to the lower lipid levels. A diverse number of protein identified for managing diabetes such as α-glucosidase, peroxisome proliferator-activated receptor-gamma (PPAR-γ) [18,19], sodium glucose cotransporter-2, dipeptidyl peptidase-IV, glucokinase, glucagon-like peptide-I [7,20,21], adenosine monophosphate activated protein kinase [22], and G proteincoupled receptor-119 (GPR-119) [23] and so on but PPARs snatching its importance as being a target protein for hyperlipidemia also.…”