Design, synthesis and evaluation of novel 2,2-dimethyl-2,3-dihydroquinolin-4(1H)-one based chalcones as cytotoxic agents

Abstract

We designed and synthesised a series of novel chalcones, incorporating the heterocyclic framework of 2,2-dimethyl-2,3-dihydro-4(1H)-quinolinone, which was prepared via Sonogashira coupling of a substituted orthoaniline under aqueous conditions using Pd catalysis followed by acid-mediated cyclisation. The compounds were screened against the NCI-N87 and DLD-1 cancer cell lines, with most compounds showing low micromolar cytotoxic activity.

Recent Updates on Synthetic Strategies of Chalcone Scaffold and their Heterocyclic Derivatives

“…Sonogashira coupling is described as the combining of alkynes to phenyl halides substituted with an electron-withdrawing group in the existence of palladium catalysis and a catalytic quantity of cuprous iodide (CuI) by reflux in a mixture of (TEA) and THF up to 24 hours under an inert atmosphere of nitrogen [ 38 ]. Many targeted chalcones were produced with good to excellent yield under these parameters [39][40][41][42]. Nevertheless, Sonogashira coupling involves significant drawbacks, such as long reaction periods, a large amount of base, and the requirement for electrondeficient aromatic halide.To address these problems, a microwave-aided coupling isomerization process was reported for chalcones production in high yield in less than 30 minutes [ 43 ].…”

Synthesis and evaluation of novel chromanone and quinolinone analogues of uniflorol as anti-leishmanial agents

“…To produce quinolinone analogues (14a-g), an alternative strategy was adopted (Scheme 4). Iodination of cyanoaniline 34 afforded 35, which was acetylated prior to Sonogashira coupling under aqueous conditions to afford alkyne 37 [31]. Acid-mediated cyclisation gave quinolinone 38, whose nitrile group was reduced analogously to that of 31, and similarly, any over-reduced alcohol could be selectively oxidised to 39 using Jones reagent.…”

Chemistry and synthetic methodologies of chalcones and their derivatives: A review

“…-chloroquinolinyl chalcones were synthesized by the condensation of 2-chloro-3-formyl quinolines with respective acetophenones in the presence of the catalytic amount of sodium hydroxide under stirring conditions for 6-24 h[60] (Scheme 38). To a solution of 6-acetyl-2,2-dimethyl-2,3-dihydroquinolin-4(H)-one, different substituted benzaldehydes were added and stirred at room temperature for 48 h, resulted in the formation of the required quinolinoylchalcone derivatives[61] (Scheme 39). These two schemes are given in Figure12.…”