Synthesis of a New Series of Furopyranone‐ and Furocoumarin‐Chromone Conjugates Followed by In–Vitro Cytotoxicity Activity Evaluation, and Molecular Docking Study

Abstract

In this work, new furopyranone‐ and furocoumarin‐chromone conjugates were successfully synthesized via the one‐pot three‐component condensation reactions of 3‐formylchromone derivatives, 4‐hydroxy‐6‐methylpyrone or 4‐hydroxycoumarin and alkyl or aryl isocyanides in refluxing toluene within 2 h. Molecular docking studies on cyclooxygenase enzymes (COX‐1, COX‐2) indicated that most derivatives have greater or moderate binding affinities than 3‐formylchromone which was used as a reference compound. Even some of the new products showed comparable binding energy towards the relative co‐crystalized ligand into COX‐1 and COX‐2. In general, all of the new products formed one to three hydrogen bonds with amino acid residues in the active site of both enzymes. Furthermore, the cytotoxicity activity of some selected compounds was investigated against human foreskin fibroblast cells (BJ) and human breast cancer cells (MDA‐MB‐231) using the MTT assay. All selected compounds exhibited significant cell growth inhibitory against cancerous cells with varied potencies when compared to 3‐formylchromone. However, they were much less toxic against normal cells.

Recent Advances on Sustainable Synthesis of Furocoumarins

“…designed a methodology for the synthesis of furocoumarin‐chromone with the help of a three‐component reaction of 3‐formyl‐chromones, 4‐ hydroxycoumarin and alkyl or aryl isocyanides in presence of toluene under refluxing conditions ( Scheme 40). [81] …”

Agarwood—The Fragrant Molecules of a Wounded Tree

“…Furthermore, chromones are considered naturally available products with diverse structures and functions that act as potential candidates for replacing synthetic drugs in various pharmacological therapeutics [ 89 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 ]. Similarly, Duan et al [ 127 ] and Vanguru et al [ 128 ] have reported the therapeutic properties of chromones against a wide range of cancers, especially in controlling breast cancer and ovarian cancer [ 129 , 130 ]. They act as intercellular adhesion molecule inhibitors, cyclooxygenase inhibitors, mast cell stabilizers, leukotriene receptor antagonists, interleukin-5 inhibitors, lipoxygenase inhibitors, and nitric oxide production inhibitors controlling inflammation as potential anti-inflammatory compounds [ 92 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 ].…”

Synthesis of heterocyclic analogs of isoflavone and homoisoflavone based on 3-formylchromone

“…40 Three-component reaction of 3-formylchromones 1, isocyanide, and either 4-hydroxycoumarin (10) or 4-hydroxy-6-methylpyran-2-one (11) in refl uxing toluene for 2 h gave furocoumarin and furopyranone isofl avone derivatives 12 (Scheme 2). 41 The authors suggest that the reaction proceeded as [4+1] cycloaddition of isocyanide to the Knoevenagel adduct 13 that generated in the reaction of 3-formylchromones 1 with compounds 10 and 11. 41 Product 12 exists in the more stable enamine form.…”

“…41 The authors suggest that the reaction proceeded as [4+1] cycloaddition of isocyanide to the Knoevenagel adduct 13 that generated in the reaction of 3-formylchromones 1 with compounds 10 and 11. 41 Product 12 exists in the more stable enamine form.…”