Structural simplification of bioactive natural products with multicomponent synthesis. 4. 4H-Pyrano-[2,3-b]naphthoquinones with anticancer activity

Abstract

4H-Pyrano-[2,3-b]naphthoquinone is a structural motif commonly found in natural products manifesting anticancer activities. As part of a program aimed at structural simplification of bioactive natural products utilizing multicomponent synthetic processes, we developed a compound library based on this heterocyclic scaffold. We found that several library members displayed low micromolar antiproliferative activity and induced apoptosis in human cancer cells. Selected compounds showed promising activity against cancer cell lines resistant to proapoptotic stimuli, demonstrating their potential in treating cancers with dismal prognoses.

Synthesis, Biological Assessment and Molecular Modeling of Racemic QuinoPyranoTacrines for Alzheimer's Disease Therapy

“…First of all, commercial 2‐hydroxynaphthalene‐1,4‐dione ( 1 ) reacted with the appropriate substituted benzaldehydes, and malononitrile ( 2 ), in the presence of catalytic amounts of piperidine, in ethanol, at reflux, to give the 14‐amino‐13‐aryl‐2,3,4,13‐tetrahydro‐1 H ‐benzo,chromene [2,3– b ] quinoline‐7,12‐diones 3–12 . Only intermediate 2‐amino‐4‐(2‐fluorophenyl)‐5,10‐dioxo‐5,10‐dihydro‐4 H ‐benzo[ g ]chromene‐3‐carbonitrile ( 10 ) has been synthesized here for the first time ( Supporting Information ).…”

Design, synthesis and preliminary structure–activity relationship investigation of nitrogen-containing chalcone derivatives as acetylcholinesterase and butyrylcholinesterase inhibitors: a further study based on Flavokawain B Mannich base derivatives

“…As shown in Figure 2, it appeared that some of the new synthesized chalcone derivatives (compounds 6c, 6d, 7a and 7b) exhibited 5-10 folds inhibitory activities against AChE than relative Flavokawain B Mannich base derivatives which were reported in our previous investigation. For the modification or optimization of flavokawain B Mannich base derivatives, structure simplification was employed, which was a widely used method in the drug discovery and development [19][20][21] . This method is benefit for the screening for pharmacophore or important structure domain in natural products, enhancing bioactivity or attenuating side effects.…”

Structural simplification: an efficient strategy in lead optimization

“…Magedov et al . 62 developed a three-component reaction of 2-hydroxy-1,4-naphthoquinone ( 23 ) with malononitrile ( 25 ) and various aromatic aldehydes ( 24 ) to efficiently construct a library of compounds with simplified pyranonaphthoquinone scaffolds ( 26 , Fig. 5).…”