From Natural Products to New Synthetic Small Molecules: A Journey through the World of Xanthones

Abstract

This work reviews the contributions of the corresponding author (M.M.M.P.) and her research group to Medicinal Chemistry concerning the isolation from plant and marine sources of xanthone derivatives as well as their synthesis, biological/pharmacological activities, formulation and analytical applications. Although her group activity has been spread over several chemical families with relevance in Medicinal Chemistry, the main focus of the investigation and research has been in the xanthone family. Xanthone derivatives have a variety of activities with great potential for therapeutic applications due to their versatile framework. The group has contributed with several libraries of xanthones derivatives, with a variety of activities such as antitumor, anticoagulant, antiplatelet, anti-inflammatory, antimalarial, antimicrobial, hepatoprotective, antioxidant, and multidrug resistance reversal effects. Besides therapeutic applications, our group has also developed xanthone derivatives with analytical applications as chiral selectors for liquid chromatography and for maritime application as antifouling agents for marine paints. Chemically, it has been challenging to afford green chemistry methods and achieve enantiomeric purity of chiral derivatives. In this review, the structures of the most significant compounds will be presented.

Xanthones Active against Multidrug Resistance and Virulence Mechanisms of Bacteria

“…Reserpine and carbonyl cyanide 3-chlorophenylhydrazone (CCCP) were used as positives control for S. aureus 272123 and SE03, respectively, at the sub-MIC concentration of 25 µM. [1][2][3][4][5][6][7][8][9][10][11] The value of the positive control in each different assay. SD: standard deviation.…”

“…Xanthones are heterocyclic polyphenolic compounds that can be found in microorganisms, fungi, lichens, and some in higher plants and marine sources, with several naturally and synthetically occurring derivatives revealing potent antimicrobial activities over the last few decades [10][11][12]. In recent works, our group described the synthesis of a series of novel nature-inspired chlorinated xanthones [13], and further transformations on the xanthone core in order to achieve a diverse library in terms of molecular function, containing carboxylic acid, ester, methyl, methoxy, phenol, bromo, and amine moieties [14].…”

Antimicrobial Activity of a Library of Thioxanthones and Their Potential as Efflux Pump Inhibitors

“…Thioxanthones are compounds that possess a dibenzo-γ-pyrone, tricyclic scaffold, they are privileged structures [10] and they have previously been described as capable of modulating the human efflux pump P-gp [11]. Thioxanthones have also demonstrated their potential as antimicrobials and have proved to be effective in enhancing the activity of antibiotics in resistant bacterial strains [12].…”

Sparstolonin B exerts beneficial effects on prostate cancer by acting on the reactive oxygen species‐mediated PI3K/AKT pathway

“…Both X‐ray crystallography and nuclear magnetic resonance spectroscopy have revealed that SsnB, whose structural formula is C 15 H 8 O 4 , is a polyphenol (Figure 1A) containing two core components of xanthone and isocoumarin 10 . Xanthones have established antioxidant, anti‐inflammatory, immunomodulatory, anti‐tumour, antimicrobial, anticholinesterase and anticonvulsant functions 11‐14 . Similarly, Isocoumarins have anti‐tumour, anticoagulant, anti‐diabetes and antimicrobial bioactivities 15,16 .…”