Bioactive Aurones, Indanones, and Other Hemiindigoid Scaffolds: Medicinal Chemistry and Photopharmacology Perspectives

Abstract

Hemiindigoids comprise a range of natural and synthetic scaffolds that share the same aromatic hydrocarbon backbone as well as promising biological and optical properties. The encouraging therapeutic potential of these scaffolds has been unraveled by many studies over the past years and uncovered representants with inspiring pharmacophoric features such as the acetylcholinesterase inhibitor donezepil and the tubulin polymerization inhibitor indanocine. In this review, we summarize the last advances in the medicinal potential of hemiindigoids, with a special attention to molecular design, structure–activity relationship, ligand-target interactions, and mechanistic explanations covering their effects. As their strong fluorogenic potential and photoswitch behavior recently started to be highlighted and explored in biology, giving rise to the development of novel fluorescent probes and photopharmacological agents, we also discuss these properties in a medicinal chemistry perspective.

Rhodanine-Based Chromophores: Fast Access to Capable Photoswitches and Application in Light-Induced Apoptosis

“…A recent survey has further emphasized the potential of hemiindigoid chromophores as photopharmacological tool that still lies dormant. [19] In this work we present a new class of related, yet distinctive photoswitches with unique potential for applications especially in biomedical context. Rhodanine-based [20] photoswitches inherit parts of the hemithioindigo (HTI) motive [21] but the benzannulated thioindigo-fragment is replaced with a rhodanine or oxo-rhodanine unit to which the stilbene fragment is connected (Figure 1a).…”

An Expedient Synthesis of Functionalized Pyrazole‐Based Aurone Analogs

“…Also, furan‐ or indole‐based aurone analogs show the anthelmintic action, which may be used in the development of new therapies for schistosomiasis [10] (Figure 1). The last advances in the medicinal potential of hemiindigoids (including aurones and their heterocycle‐based analogs), structure‐activity relationship, ligand‐target interactions, and mechanistic explanations have been summarized in a recent review [11] …”

“…The last advances in the medicinal potential of hemiindigoids (including aurones and their heterocycle-based analogs), structure-activity relationship, ligand-target interactions, and mechanistic explanations have been summarized in a recent review. [11] Moreover, pyrazole and its derivatives are one of the most important heterocyclic moieties in medicinal chemistry, possessing a broad spectrum of pharmacological activities. [12] Replacing of aromatic B-ring of aurone with a pyrazole ring could be an attractive pathway for the development of new pharmacologically promising compounds.…”

Accessing 7‐Azaaurones of Controllable E and Z Configurations from 8‐Azaflavones via a Rearrangement‐Acylation‐Photoisomerization Sequence

“…Comparatively, ring A has been less explored, with only old reports on 5‐aza [4] and 7‐azaaurones [5] . This is likely attributable to a lack of synthetic methodologies rather than a lack of interest, considering the numerous biological activities (including anti‐inflammatory, antiviral, antioxidant, and anticancer) and optical properties (fluorescence and photoswitching) of aurones and aza analogues, and the potential applications in chemical biology and medicinal chemistry [6] …”