Gannerla Saidachary

α-Glucosidase inhibitory antihyperglycemic activity of substituted chromenone derivatives

Series of 3,4- and 3,6-disubstituted chromenones including new chromenone derivatives were synthesized applying various synthetic strategies including Pechmann condensation, Knoevenagel condensation, Reimer-Tiemann reaction and Suzuki coupling in very good yields. Synthesized compounds (4a-z) were screened for in vitro alpha-glucosidase inhibitory and 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activities. Majority of compounds displayed varying degrees of alpha-glucosidase inhibitory and DPPH scavenging activity. Compound 4x emerged as the most potent alpha-glucosidase inhibitor in present series of compounds owing to the presence of 3-acetyl-6-(6-methoxy-3-pyridyl) group on chromenone; however, it could not display DPPH scavenging activity and was found to be mixed non-competitive type inhibitor of rat intestinal alpha-glucosidase. When tested in vivo for antihyperglycemic activity in starch loaded Wistar rats, it displayed significant antihyperglycemic property. This is the first report assigning rat intestinal alpha-glucosidase inhibitory property for this class of new chromenones and presents new family of compounds possessing alpha-glucosidase inhibitory activities and antihyperglycemic property. Compound 4x may serve as an interesting new compound for the development of therapeutics targeted against diet-induced hyperglycemia in diabetes.

Synthesis, anticancer activity and photophysical properties of novel substituted 2-oxo-2H-chromenylpyrazolecarboxylates.

2-Oxo-2H-chromenylpyrazolecarboxylates (8a-h and 12a-zb) have been synthesized by [3 + 2] cycloaddition of 2H-chromenophenylhydrazones (7a-h and 11a-w) with diethyl/dimethylbut-2-ynedioates. Phenylchromeno[4,3-c]pyrazol-4(1H)-ones (13i-n) were prepared from corresponding phenylhydrazones (7a-h) with catalytic amount of piperidine in presence of pyridine as a solvent at 100 °C. All the synthesized compounds (8a-h, 12a-zb and 13a-n) were screened for anticancer activity against three human cancer cell lines such as prostate (DU-145), lung adenocarcinoma (A549), and cervical (HeLa) by standard MTT assay method. Further, photophysical properties (UV and fluorescence) for these compounds were discussed.

A Novel Approach for C–C, C–N, and C–O Bond Formation Reactions: A Facile Synthesis of Benzophenazine, Quinoxaline, and Phenoxazine Derivatives via Ring Opening of Benzoxepines

A new one-pot protocol has been developed for the synthesis of benzophenazine, quinoxaline, and phenoxazine derivatives by the reaction of benzoxepine-4-carboxylates with benzene-1,2-diamines, ethane-1,2-diamine, and 2-aminophenols in the presence of Bi(OTf)3 (5 mol %) under mild conditions in very good yields. The present protocol opens a new way for C-C, C-N, and C-O bond-formation reactions in a single-step process. The structural assignment was confirmed by X-ray analysis.

New convenient approach for the synthesis of benzyl 2H-chromenones and their α-amylase Inhibitory, ABTS.+ scavenging activities.

Series of new benzyl 2H-chromenones 6a-n was synthesized by Pechmann condensation of substituted benzyl resorcinols 2a-c and 3a with various β-ketoesters such as ethyl 3-oxobutanoate, ethyl 3-oxo-3-phenylpropanoate, ethyl 4- chloro-3-oxobutanoate, ethyl 4,4,4-trifluoro-3-oxobutanoate and ethyl 2-chloro-3-oxobutanoate 5a-e in very good yields. Synthesized compounds 6a-n were screened for their α-amylase inhibitory, and ABTS.+ scavenging activities. In the present series of compounds, compound 8-benzyl-7-hydroxy-4-phenyl-2H-chromen-2-one 6c and 8-benzyl-7-hydroxy-4- methyl-2H-chromen-2-one 6a were most potent ABTS.+ radical scavenging and α-amylase inhibitor. Although compound 6,8-dibenzyl-7-hydroxy-4-(trifluoromethyl)-2H-chromen-2-one 6h displayed potent ABTS.+ free radical scavenging potential, it was found poor in inhibiting pancreatic α-amylase.

Pancreatic α-amylase inhibition and free radical scavenging activity of substituted pyranochromenone derivatives

Pyranochromenone derivatives 3a–d, 6a–j and 2H-chromenones 8a–b were synthesized and screened for their in vitro α-amylase inhibitory and ABTS•+ [2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)] free radical scavenging activities. Compounds 3a, 3c, and 6d displayed dual function of ABTS•+ radical scavenging as well as α-amylase inhibition. Compound 6h was found to be most potent α-amylase inhibitor in present series of compounds. Docking studies suggest that these compounds occupy active site of the human pancreatic α-amylase similar to that of acarbose which inhibits enzyme by hydrophobic interactions. These compounds have potential to be developed as therapeutics targeted against diet-induced hyperglycemia in diabetes.Graphical abstractSeries of pyranochromenone derivatives 3a–d, 6a–j, and 8a–b were synthesized, among these compound 6h shown potent intestinal α-amylase inhibitory activity. Compounds 3a, 3c, and 6d were shown dual properties such as α-amylase inhibitory and antioxidant activities. These derivatives may serve as a model compounds for design and development of therapeutics based agents.