Molecular medicinal insights into scaffold hopping-based drug discovery success

Acharya, Ayan; Yadav, Mukul; Nagpure, Mithilesh; Kumaresan, Sanathanalaxmi; Guchhait, Sankar K.

doi:10.1016/j.drudis.2023.103845

Cited by 10 publications

(2 citation statements)

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“…Despite this, considering their unfavorable P3 properties, an acceptable drug-likeness is still far from being achieved [ 5 ]. In this light, the scaffold-hopping method is probably one of the most interesting approaches to be pursued in the lead optimization of natural compounds [ 14 , 15 , 16 , 17 , 18 ].…”

Section: Discussionmentioning

confidence: 99%

“…Another promising approach in optimizing natural compounds involves scaffold hopping, which entails substituting the central scaffold of a lead compound with a bioisosteric core to discover more potent compounds with improved P3 features [ 14 , 15 , 16 , 17 , 18 ]. In this context, to the best of our knowledge, there is a dearth of the literature reviewing whether such optimization strategies positively impact aurone compounds.…”

Section: Introductionmentioning

confidence: 99%

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Scaffold-Hopping Strategies in Aurone Optimization: A Comprehensive Review of Synthetic Procedures and Biological Activities of Nitrogen and Sulfur Analogues

La Monica,

Alamia,

Bono

et al. 2024

Molecules

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Aurones, particular polyphenolic compounds belonging to the class of minor flavonoids and overlooked for a long time, have gained significative attention in medicinal chemistry in recent years. Indeed, considering their unique and outstanding biological properties, they stand out as an intriguing reservoir of new potential lead compounds in the drug discovery context. Nevertheless, several physicochemical, pharmacokinetic, and pharmacodynamic (P3) issues hinder their progression in more advanced phases of the drug discovery pipeline, making lead optimization campaigns necessary. In this context, scaffold hopping has proven to be a valuable approach in the optimization of natural products. This review provides a comprehensive and updated picture of the scaffold-hopping approaches directed at the optimization of natural and synthetic aurones. In the literature analysis, a particular focus is given to nitrogen and sulfur analogues. For each class presented, general synthetic procedures are summarized, highlighting the key advantages and potential issues. Furthermore, the biological activities of the most representative scaffold-hopped compounds are presented, emphasizing the improvements achieved and the potential for further optimization compared to the aurone class.

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