Effect of Peroxisomicine and Related Anthracenones on Catalase Activity

Abstract

Dimeric anthracenones were isolated from toxic plants of the genus Karwinskia (Rhamnaceae). T 514 or peroxisomicine A1 is one of these toxic compounds which produces an irreversible and selective damage on the peroxisomes of yeast cells in vivo. In this paper we now report the inhibitory effect in vitro of peroxisomicine A1 and other structurally related anthracenones on liver catalase activity. The peroxisomicine A1 produces a non-competitive inhibition with respect to H2O2 on bovine, dog, and mouse liver catalases. In the three cases Vmax was decreased whereas Km was unaffected. Other dimeric anthracenones of natural origin were also found to be inhibitors of bovine liver catalase. There is a relationship between structure and degree of inhibition of all anthracenonic compounds tested. Peroxisomicine A1 and peroxisomicine A2 caused the highest degree of inhibition (IC50 = 3.34 and 3.64 microM, respectively).

Karwinaphthopyranones from the Fruits of Karwinskia parvifolia and Their Cytotoxic Activities

“…10 PA1 was also found to inhibit catalase in vitro. 11 Minor diastereomers of PA1 have also been reported. 12,13 Bis-anthracenone T-478 (9) was obtained previously chemically by dehydration of peroxisomicine A1 (8), when treated with HCl in acetic acid.…”

“…T-514 was renamed peroxisomicine A1 (PA1) because it was found to cause an irreversible and selective damage of yeast peroxisomes in vivo . PA1 was also found to inhibit catalase in vitro . Minor diastereomers of PA1 have also been reported. , Bis-anthracenone T-478 ( 9 ) was obtained previously chemically by dehydration of peroxisomicine A1 ( 8 ), when treated with HCl in acetic acid…”

Effect of peroxisomicine A2and T 544 of the genusKarwinskiaon peroxisomes ofCandida boidinii

“…As previously described for peroxisomicine A 1 , peroxisomicine A 2 and T 544 also produced disruption of the peroxisomal membrane, T 544 being the most active of the three compounds. We have previously reported the inhibitory effect in vitro of structurally related anthracenones, among them peroxisomicine A 1 , peroxisomicine A 2 and T 544, on liver catalase activity [6]. Recently, we also demonstrated that peroxisomicine A 1 was not able to inhibit the catalase activity in intoxicated mice, in vivo [7].…”

“…For this reason we renamed it peroxisomicine A 1 . Recently, we reported the inhibitory effect in vitro of peroxisomicine A 1 and structurally related anthracenones on liver catalase activity, using the purified enzyme [6]. In contrast to the described findings in vitro, peroxisomicine A 1 is not able to inhibit in vivo the activity of catalase in methylotrophic yeasts with peroxisomal damage induced by the toxin [5], either in hepatic fragments incubated with this toxin (in situ) or in intoxicated mice (in vivo) [7].…”

Toxicity and Anticancer Potential of Karwinskia: A Review

“…Several works have been carried out in order to deepen in the mechanism of action of PA1 as a potential anticancer agent. Since CAT is a peroxisomal marker enzyme, Moreno-Sepúlveda et al [90] evaluated the effect in vitro of PA1 on bovine, mouse, and dog liver CAT activity. PA1 inhibited the activity of CAT from the three animal sources in a non-competitive way.…”