Mode of action and pesticidal activity of the natural product dunnione and of some analogues

Abstract

This paper reports the investigation of the insecticidal and fungicidal activity of dunnione, a natural product obtained inadvertently as a by-product of a synthesis programme. Dunnione exhibits no insecticidal activity but has an unusually broad spectrum of antifungal activity. In vitro and in vivo (preventative) activities were comparable to those of several long-established fungicides (eg carbendazim). However, in whole-plant assays, its eradicant activity was unexpectedly low, probably due to poor dose-transfer from leaf surface to fungus. The level of residual activity appears to be influenced by the formulation. Finally, its potential as a lead structure was assessed, and several analogues synthesised which exhibited high activity in the in vitro assays. Mode-of-action studies revealed that dunnione exerts its action primarily through initiation of redox cycling. This contrasts to the activity of BTG 505, the biochemical/chemical precursor, which does not initiate redox cycling but instead exhibits both insecticidal and fungicidal activity by inhibiting mitochondrial Complex III.

Plant Natural Products as a Source for Developing Environmentally Acceptable Insecticides

“…They offer opportunities both as lead structures for analogue synthesis (Khambay et al 1997a) and as new botanical pesticides (Khambay et al 1997b) exhibiting low mammalian toxicity unlike other naphthoquinones. The use of the compounds as pesticides has been patented (Khambay et al 1999) by BTG International Ltd. Khambay et al (2003) compared the insecticidal and fungicidal properties of dunnione (a known naphthoquinone) with BTG 505 (4, Fig. 2).…”

“…Although, dunnione showed practically no activity against the house fly Musca domestica, the whitefly B. tabaci, the beetle Phaedon cochleariae, or the spider mite T. urticae unlike BTG 504 and BTG 505, dunnione has an unusually broad spectrum of antifungal activity. The mode of action of dunnione is primarily through initiation of redox cycling, whereas, BTG 505 acts by inhibiting mitochondrial complex III (Khambay et al 2003).…”

Phytochemical Pesticides

“…Although dunnione showed practically no activity against the housefl y, Musca domestica , the whitefl y B. tabaci , the beetle Phaedon cochleariae , or the spider mite T. urticae unlike BTG 504 and BTG 505, dunnione has an unusually broad spectrum of antifungal activity. The mode of action of dunnione is primarily through initiation of redox cycling, whereas BTG 505 acts by inhibiting mitochondrial complex III (Khambay et al 2003 ).…”

“…The primary mode of action in insects is by inhibition of complex III of the mitochondrial respiratory chain (Khambay and Jewess 2000 ). The insecticidal and fungicidal properties of dunnione (a known naphthoquinone) with natural BTG 505 have been compared (Khambay et al 2003 ). Although dunnione showed practically no activity against the housefl y, Musca domestica , the whitefl y B. tabaci , the beetle Phaedon cochleariae , or the spider mite T. urticae unlike BTG 504 and BTG 505, dunnione has an unusually broad spectrum of antifungal activity.…”

Inhibitory effects of a β-dunnione compound MB12662 on gastric secretion and ulcers

“…[6], and found out their potential antioxidative activity (unpublished results). A β-lapachone MB12066 decreased gastric secretion and acidity [7], and a β-dunnione MB12662 substantially alleviated cisplatin-induced intestinal necrosis (unpublished results).…”