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[Display omitted] • Isoflavone analogues were synthesized from benzoylbenzofuran precursors. • Benzoylbenzofurans and isoflavones inhibited MDA-MB-231 cancer cell proliferation. • Isoflavone derivatives were discovered as potent sirtuin 1 inhibitors. • Isoflavone quinone 39 displayed sirtuin 1 inhibitory activity comparable to that of suramin. • In silico docking studies revealed the binding modes of the active sirtuin 1 inhibitors. Isoflavone derivatives were prepared from benzoylbenzofuran precursors. The synthesized compounds were analyzed by 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, as well as high-resolution mass spectrometry (HRMS) to confirm their structures. The benzoylbenzofuran and isoflavone analogues were evaluated for inhibition of sirtuin 1 (SIRT1) and cell proliferation in MDA-MB-231 triple-negative breast cancer (TNBC) cells. Several isoflavone and benzoylbenzofuran derivatives exhibited potent antiproliferative effects against the MDA-MB-231 cancer cell line. Most of the isoflavone derivatives attenuated SIRT1 activity to below 50%. The most active compounds were the isoflavone quinones 38 , 39 , and 40 , at IC 50 values of 5.58 ± 0.373, 1.62 ± 0.0720, and 7.24 ± 0.823 μM, respectively. Importantly, the most active compound, 6-methoxy-4′,6′-dimethylisoflavone-2′,5′-quinone (39) displayed SIRT1 inhibitory activity comparable to that of the reference compound, suramin. The in silico docking simulations in the active site of SIRT1 further substantiated the experimental results and explored the binding orientations of potent compounds in the active site of the target. [ABSTRACT FROM AUTHOR]

[Display omitted] • A new series of 1,3,4-thiadiazole-thiazolidine-4-one molecular hybrids were developed. • A three-component reaction was established in the presence of p -toluene sulfonyl chloride and triethylamine. • The synthesized hybrids were screened for their antidiabetic, antioxidant and antimicrobial activities. • Compound 4e bearing a para -thiomethyl unit showed the most potent inhibition of α -glucosidase and α -amylase. A simple and efficient protocol was developed to synthesize a new library of thiazolidine-4-one molecular hybrids (4a-n) via a one-pot multicomponent reaction involving 5-substituted phenyl-1,3,4-thiadiazol-2-amines, substituted benzaldehydes and 2-mercaptoacetic acid. The synthesized compounds were evaluated in vitro for their antidiabetic activities through α -glucosidase and α -amylase inhibition as well as their antioxidant and antimicrobial potentials. Compound 4e exhibited the most promising α -glucosidase and α -amylase inhibition with an IC 50 value of 2.59 μM, which is ~1.5- and 14-fold superior as compared to the standard inhibitor acarbose. Structure-activity relationship (SAR) analysis revealed that the nature and position of substituents on the phenyl rings had a significant effect on the inhibitory potency. [ABSTRACT FROM AUTHOR]

[Display omitted] • 1 H -1,2,3-triazole tethered tacrine-chalcone conjugates and evaluation of their AChE inhibitory activity. • The most potent compounds exhibited in-vitro IC 50s value more than drug tacrine. • In-vivo Scopolamine induced Inclined plane and Elevated plus-maze models. • Evaluation of biochemical parameters GSH and TBARS. • Docking studies were performed to delineate the mechanism of action. The present paper explicates the synthesis of 1 H -1,2,3-triazole tethered tacrine-chalcone conjugates and evaluation of their AChE and BuChE inhibitory activity. In-vitro AChE inhibition assay revealed three compounds, 9h , 9i, and 11f , being more potent than the standard drug tacrine and further evaluated against butyrylcholinesterase. The present study was extended to investigate the anti-amnestic effect of promising compounds on scopolamine-induced behavioral and neurochemical changes in mice. Inclined plane model and Elevated plus-maze model were performed to assess general limb motor activity and anxiety-like behavior, respectively, in mice pre-treated with scopolamine. Oxidative stress parameters reduced glutathione contents (GSH) and lipid peroxidation products (TBARS) in the brain homogenates as estimated using ex-vivo studies. Furthermore, molecular docking studies were performed for the potent compounds to decipher the mechanism of observed activities. [ABSTRACT FROM AUTHOR]