Recent Trends in the Synthesis and Bioactivity of Coumarin, Coumarin–Chalcone, and Coumarin–Triazole Molecular Hybrids

Abstract

Molecular hybridization represents a new approach in drug discovery in which specific chromophores are strategically combined to create novel drugs with enhanced therapeutic effects. This innovative strategy leverages the strengths of individual chromophores to address complex biological challenges, synergize beneficial properties, optimize pharmacokinetics, and overcome limitations associated with single-agent therapies. Coumarins are documented to possess several bioactivities and have therefore been targeted for combination with other active moieties to create molecular hybrids. This review summarizes recent (2013–2023) trends in the synthesis of coumarins, as well as coumarin–chalcone and coumarin–triazole molecular hybrids. To cover the wide aspects of this area, we have included differently substituted coumarins, chalcones, 1,2,3– and 1,2,4–triazoles in this review and considered the point of fusion/attachment with coumarin to show the diversity of these hybrids. The reported syntheses mainly relied on well-established chemistry without the need for strict reaction conditions and usually produced high yields. Additionally, we discussed the bioactivities of the reported compounds, including antioxidative, antimicrobial, anticancer, antidiabetic, and anti-cholinesterase activities and commented on their IC50 where possible. Promising bioactivity results have been obtained so far. It is noted that mechanistic studies are infrequently found in the published work, which was also mentioned in this review to give the reader a better understanding. This review aims to provide valuable information to enable further developments in this field.

Synthesis, Molecular Electron Density Theory Study, Molecular Docking, and Pharmacological Evaluation of New Coumarin–Sulfonamide–Nitroindazolyl–Triazole Hybrids as Monoamine Oxidase Inhibitors

“…Based on the previous studies describing the inhibition of monoamine oxidase and cholinesterase exerted by indazoles [ 37 ], 1,2,3-triazole–coumarin hybrids [ 38 , 39 , 40 ], and arylsulfonamides [ 41 , 42 ], this research aims to contribute to the development of novel molecule conjugates by exploring the linkage of a coumarin bearing a nitro group to sulfonamide and indazole, through simple and efficient synthetic routes, such as reduction, coupling reactions, and a copper-azide-alkyne-cycloaddition (CuAAC) methodology in order to prepare and evaluate the potential of new hybrids as neuroprotective agents. The drug design derives from previous studies with coumarins and related compounds (e.g., benzodioxine), which have revealed marked anti-inflammatory properties [ 43 , 44 ].…”