Chalcone Derivatives: Promising Starting Points for Drug Design

Abstract

Medicinal chemists continue to be fascinated by chalcone derivatives because of their simple chemistry, ease of hydrogen atom manipulation, straightforward synthesis, and a variety of promising biological activities. However, chalcones have still not garnered deserved attention, especially considering their high potential as chemical sources for designing and developing new effective drugs. In this review, we summarize current methodological developments towards the design and synthesis of new chalcone derivatives and state-of-the-art medicinal chemistry strategies (bioisosterism, molecular hybridization, and pro-drug design). We also highlight the applicability of computer-assisted drug design approaches to chalcones and address how this may contribute to optimizing research outputs and lead to more successful and cost-effective drug discovery endeavors. Lastly, we present successful examples of the use of chalcones and suggest possible solutions to existing limitations.

Structure–activity relationship investigation of coumarin–chalcone hybrids with diverse side-chains as acetylcholinesterase and butyrylcholinesterase inhibitors

“…Chalcones, for example, are promising natural product scaffolds for drug development and exhibit a wide variety of bioactivities including anti-obesity, anti-inflammatory and anti-gout activities. For example, the chalcones metochalcone and sofalcone, Figure 1, have been used in the clinic as choleretic and anti-ulcer agents, respectively [10]. Flavokawain B, first isolated from Piper methysticum Forst [11] is another natural product containing the chalcone scaffold.…”

Synthesis and in vitro Evaluation of 2-heteroarylidene-1-tetralone Derivatives as Monoamine Oxidase Inhibitors

“…Traditional medicinal use of chalcone-containing plants led to the discovery of their potential therapeutic applications. Chalcones possess a broad spectrum of pharmacological activities including antimalarial, anticancer, anti-inflammatory, antifungal, antimicrobial, antioxidant and chemopreventive activities [14,15]. Of interest to us are reports that chalcones act as inhibitors of the MAO enzymes.…”

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“…The use of herbal medicines continues to expand rapidly across the world. As a result of pharmacological studies, several pure chalcones isolated from different plants have been approved for clinical trials for treatment of cancer, viral and cardiovascular disorders or have been included as ingredients in cosmetic preparations 72,73 . Polyphenols represent one of the most prevalent classes of compounds found in our daily diet.…”