Pochonicine, a polyhydroxylated pyrrolizidine alkaloid from fungus Pochonia suchlasporia var. suchlasporia TAMA 87 as a potent β-N-acetylglucosaminidase inhibitor

Scalable Syntheses of Both Enantiomers of DNJNAc and DGJNAc from Glucuronolactone: The Effect of N‐Alkylation on Hexosaminidase Inhibition

“…Although there are many naturally occurring hydroxylated piperidines that are related to sugars in which the oxygen atom of the pyranose ring has been replaced by a nitrogen atom,1 neither DGJNAc (2‐acetamido‐1,2‐dideoxy‐ D ‐ galacto ‐nojirimycin, 1 D ) nor DNJNAc (2‐acetamido‐1,2‐dideoxy‐ D ‐ gluco ‐nojirimycin, 2 D ), which are analogues of GalNAc and GlcNAc, respectively, have yet been isolated as natural products (Figure 1). Nagstatin ( 3 ),2 which is isolated from the fermentation broth of Streptomyces amakusaensis MG846‐fF3,3 and pochonicine ( 4 ),4 which is isolated from Pochonia suchlasporia var. suchlasporia TAMA 87, are potent inhibitors of β‐hexosaminidases but show no inhibition of α‐GalNAcases.…”

A crystal structure-guided rational design switching non-carbohydrate inhibitors' specificity between two β-GlcNAcase homologs

“…Some are very potent with K i values in the μM to nM range, most of which exhibit almost no selectivity toward function-specific β-GlcNAcases. Representative examples include nagstatin18, PUGNAc19, NAG-thiazoline20, GlcNAcstatinA/B21, pochonicine2223, DNJNAc2425 and other iminocyclitols26272829. The carbohydrate-based TMG-chitotriomycin is the first reported highly-selective inhibitor against chitinolytic β-GlcNAcases from bacteria, fungi and insects, but it is not active toward glycoconjugate-lytic β-GlcNAcases from plant and human3031.…”

Anti-inflammatory Activity of Pyrrolizidine Alkaloids from the Leaves of <i>Madhuca pasquieri</i> (Dubard)

“…One of the novel PAs, pochonicine, showed potent inhibition of a variety of β-N-acetylglucosaminidases (GlcNAcases), at a level comparable to that of nagstatin, a natural inhibitor; the authors state that this is the first report of GlcNAcase inhibition by a pyrrolizidine. 15) However, PAs and their derivative compounds normally show weak cytotoxicity against various cancer cell lines. 16,6) In accordance with our present work, the cytotoxicity of the isolated PAs is also weak against cancer cell lines such as A549, PC-3, and MCF-7.…”