Chemical Properties
white to light beige crystals or powder
Uses
Gram negative bacteria utilize N-acylated homoserine lactones to coordinate expression of virulence in response to the density of the surrounding bacterial population in a process termed quorum sensing. By interfering with this communication and thereby disrupting virulence expression, quorum sensing inhibitors are emerging as an alternative to the conventional ways of fighting bacterial infections. Penicillic acid is a mycotoxin produced from Penicillium species identified in molds on corn and other grains. At 80 μM, penicillic acid inhibits bacterial quorum sensing communication in P. aeruginosa by selectively repressing various virulence factor and other quorum sensing-regulated genes. It has been shown to inhibit Fas-mediated apoptosis at 100-200 μM by targeting caspase-8 activity in Burkitt’s lymphoma Raji cells.
Description
Gram negative bacteria utilize N-acylated homoserine lactones to coordinate expression of virulence in response to the density of the surrounding bacterial population in a process termed quorum sensing. By interfering with this communication and thereby disrupting virulence expression, quorum sensing inhibitors are emerging as an alternative to the conventional ways of fighting bacterial infections. Penicillic acid is a mycotoxin produced from Penicillium species identified in molds on corn and other grains. At 80 μM, penicillic acid inhibits bacterial quorum sensing communication in P. aeruginosa by selectively repressing various virulence factor and other quorum sensing-regulated genes. It has been shown to inhibit Fas-mediated apoptosis at 100-200 μM by targeting caspase-8 activity in Burkitt’s lymphoma Raji cells.
in vitro
the compound was active primarily against gram-negative bacteria, and it was also active against some gram-positive species. it showed limited antihelminthic properties but did affect the growth of oat seed coleoptiles by interference with the respiratory process. penicillic acid has proven to be too toxic for use in therapy [1]. penicillic acid (80 μm) inhibited bacterial quorum sensing communication in p. aeruginosa by selectively repressing various virulence factor and other quorum sensing-regulated genes [2]. in burkitt’s lymphoma raji cells, penicillic acid exihibited an inhibitory effect on fas-mediated apoptosis at 100-200 μm by targeting caspase-8 activity [3].
in vivo
the ldso (subcutaneous injection) for mice is 100 mg/kg. subcutaneous injection of 1.0 mg/dose twice weekly produced transplantable tumors after 64 weeks in all rats surviving treatment. in addition, a dose at 0.1 mg initiated tumor development [1].
Purification Methods
The lactone (furanone, anhydrous) hydrolyses to the acid (3-methoxy-4-oxo-hexa-2,5-dienoic acid, hydrate). It crystallises from water as the monohydrate (acid), or from pet ether as the anhydrous (lactone) compound. The free acid is in equilibrium with the lactone. UV: max 221nm ( 12,500) in 0.02M KOH; 228nm ( 11,500) in 0.02M HCl [Raphael J Chem Soc 1508 1948]. [Beilstein 3 II 519, 3 III 1467.] It is a possible antineoplastic.
References
[1] ciegler a, detroy r w, lillehoj e b. patulin, penicillic acid, and other carcinogenic lactones[j]. microbial toxins, 1971, 6: 409-434.
[2] rasmussen t b, skindersoe m e, bjarnsholt t, et al. identity and effects of quorum-sensing inhibitors produced by penicillium species[j]. microbiology, 2005, 151(5): 1325-1340.
[3] bando m, hasegawa m, tsuboi y, et al. the mycotoxin penicillic acid inhibits fas ligand-induced apoptosis by blocking self-processing of caspase-8 in death-inducing signaling complex[j]. journal of biological chemistry, 2003, 278(8): 5786-5793.
