Structure-activity Relationships of Xanthocillin Derivatives as Thrombopoietin Receptor Agonist

Abstract

Xanthocillin derivatives, which show thrombopoietin receptor agonist activity, were synthesized through our developed method. Bioassay data suggest the importance of alkene geometry, the presence of substituents at the benzene ring that support hydrophobic character, and the moderate size of the molecule. One of the two isonitrile group of the natural product appears to be dispensable.

Chemical profile of the secondary metabolites produced by a deep-sea sediment-derived fungus Penicillium commune SD-118

“…The structureactivity relationship of xanthocillin X (1) and its derivatives indicated that the isocyanide group was not needed to sustain biological activity as a thrombopoietin receptor agonist. Removal of one isocyanide group did not destroy activity but reduced efficacy (Yamaguchi et al, 2006). The structureactivity relationship of xanthocillin X (1) as an antibacterial agent has not been reported previously and therefore deserves further study.…”

A more sustainable and highly practicable synthesis of aliphatic isocyanides

“…1 Except for a few examples, most derivatives exhibit low toxicity and interestingly, many natural isocyanides show antibiotic, fungicidal, antineoplastic, or antifouling effects. 1,2 Most commonly, they are used in isocyanide-based multicomponent reactions (IMCRs), 1,[3][4][5] which have manifold applications ranging from organic synthesis 1 to drug discovery 6,7 and polymer science. [8][9][10][11] As multicomponent reactions (MCRs) are generally considered as sustainable synthesis tools, as they fulfil many of the twelve principles of green chemistry, 5 it is important to further consider the synthesis of their starting materials in the scope of green chemistry.…”

Isonitrile Formation by a Non‐Heme Iron(II)‐Dependent Oxidase/Decarboxylase

“…Due to its ability to coordinate transition metals, it is often exploited for metal acquisition, detoxification, and virulence. 1–3 Indeed the resume of potent biologically active isonitrile containing natural products is vast, and examples include xanthocillin, an antiviral agent; 4 rhabduscin, a virulence associated phenoloxidase inhibitor; 2 and many marine sponge derived metabolites (Figure S1). Despite the widespread utility of isonitrile in nature, its biosynthesis has long been considered endemic to the IsnA family of isonitrile synthases, which typically convert an a-amino group to isonitrile on an amino acid and require ribulose-5-phosphate as a co-substrate (Figure S2).…”