naphthoquinones and oxoline

The quinoid pigment echinochrome A isolated from the sea urchin Scaphechinus mirabilis, the product of its oxidation dehydroechinochrome, and structurally similar antiviral agent oxolin were tested for their ability to inhibit plaque formation induced by herpes simplex virus type 1 (HSV-1) in Vero cells. The tested compounds showed significant anti-HSV-1 activity, mainly due to their direct effect on viral particles and on virus attachment to cells. The antiviral efficacy of the test compounds increased in the following order: oxolin→echinochrome A→dehydroechinochrome.

Topics: Animals; Antiviral Agents; Chlorocebus aethiops; Herpes Simplex; Herpesvirus 1, Human; Naphthoquinones; Oxidation-Reduction; Sea Urchins; Tetrahydronaphthalenes; Vero Cells; Virus Attachment; Virus Internalization

Hormesis occurs when a low level stress elicits adaptive beneficial responses that protect against subsequent exposure to severe stress. Recent findings suggest that mild oxidative and thermal stress can extend lifespan by hormetic mechanisms. Here we show that the botanical pesticide plumbagin, while toxic to C. elegans nematodes at high doses, extends lifespan at low doses. Because plumbagin is a naphthoquinone that can generate free radicals in vivo, we investigated whether it extends lifespan by activating an adaptive cellular stress response pathway. The C. elegans cap'n'collar (CNC) transcription factor, SKN-1, mediates protective responses to oxidative stress. Genetic analysis showed that skn-1 activity is required for lifespan extension by low-dose plumbagin in C. elegans. Further screening of a series of plumbagin analogs identified three additional naphthoquinones that could induce SKN-1 targets in C. elegans. Naphthazarin showed skn-1dependent lifespan extension, over an extended dose range compared to plumbagin, while the other naphthoquinones, oxoline and menadione, had differing effects on C. elegans survival and failed to activate ARE reporter expression in cultured mammalian cells. Our findings reveal the potential for low doses of naturally occurring naphthoquinones to extend lifespan by engaging a specific adaptive cellular stress response pathway.

Topics: Aging; Animals; Biosensing Techniques; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Gene Expression Regulation; Genes, Reporter; Green Fluorescent Proteins; Hep G2 Cells; Humans; Longevity; Mutation; Naphthoquinones; Stress, Physiological; Survival Analysis; Tetrahydronaphthalenes; Toxins, Biological; Transcription Factors; Transcription, Genetic; Vitamin K 3