Regiodivergent Access to 2- or 3-Substituted Indanones: Catalyst-Controlled Carboacylation via C–C Bond Activation

Indanones are ubiquitous in biologically active compounds.Intramolecular hydroacylation of aldehydes and alkenes is an efficient and atomeconomic route to indane rings.However,these reactions are limited to the transfer of a hydride to the alkene.The transfer of aryl groups enabling the formation of C–C bonds during the cyclization would be a new method for the synthesis of substituted indanones.This report describes the regiodivergent carboacylation of alkenes with ketones to furnish both 2-and 3-substituted indanones in a regiocontrolled manner.

Computational docking and in vitro analysis identifies novel arylidene analogue FPMXY-14 against renal cancer cells by attenuating Akt

Targeted therapies are gaining global attention to tackle Renal Cancer(RC).This study aims to screen FPMXY-14(novel arylidene analogue)for Akt inhibition by computational and in vitro methods.FPMXY-14 was subjected to proton NMR analysis and Mass spectrum analysis.Vero,HEK-293,Caki-1,and A498 cell lines were used.Akt enzyme inhibition was studied with the fluorescent-based kit assay.Modeller 9.19,Schrodinger 2018-1,LigPrep module,and Glide docking were used in computational analysis.The nuclear status was assessed by PI/Hoechst-333258 staining,cell cycle,and apoptosis assays were performed using flow cytometry.Scratch wound and migrations assays were performed.Western blotting was applied to study key signalling proteins.FPMXY-14 selectively inhibited kidney cancer cell proliferation with GI50 values of 77.5 nM and 101.40 nM in Caki-1 cells and A-498 cells,respectively.The compound dose-dependently inhibited Akt enzyme with an IC50 value of 148.5 nM and bound efficiently at the allosteric pocking of the Akt when computationally analyzed.FPMXY-14 caused nuclear condensation/fragmentation,increased the sub G_(0)/G_(1),G_(2)M populations,and induced early,late phase apoptosis in both cells when compared to controls.Treatment of the compound inhibited wound healing and migration of tumor cells,while proteins like Bcl-2,Bax,and caspase 3 were also altered.FPMXY-14 effectively inhibited the phosphorylation of Akt in these cancer cells,while total Akt was unaltered.FPMXY-14 exhibited anti-proliferative and anti-metastatic activities in kidney cancer cells by attenuating the Akt enzyme.Further pre-clinical research on animals with a detailed pathway elucidation is recommended.

Syntheses of Substituted Indan-1-onesand Indenes

The syntheses of three novel substituted indanones namely 2,7 dimethylindan 1 one, 2 methyl 4,7 diethylindan 1 one and 2,4 dimethyl 7 methoxyindan 1 one are described. These indanones were prepared by different routes involving intramolecular ring closure of aryl substituted compounds by Friedel Crafts reaction. The t butyl was used as the positional protective group in the selective preparation of 2,7 dimethylindan 1 one. The corresponding indenes were prepared by reduction and dehydration reactions from these indanones.