N-Acetylphenylisoserinates of Lactarius Sesquiterpenoid Alcohols - Cytotoxic, Antiviral, Antiproliferative and Immunotropic Activities in vitro

Abstract

In the present study a new group of derivatives of both paclitaxel and Lactarius sesquiterpenes, the N-acetylphenylisoserinates of Lactarius sesquiterpenoid alcohols, was tested for antiviral, cytotoxic, antiproliferative and immunotropic activities in vitro. Among the 13 compounds tested two, isolactarorufin 8-[N-acetyl-(2′R,3′S)-3′-phenylisoserinate] and 3-O-ethylfurandiol 8-[N-acetyl-(2′R,3′S)-3′-phenylisoserinate] inhibited Herpes simplex virus type 1 (HSV-1) replication at low cytotoxic concentrations. Selectivity indices were: > 12.2 and > 106.4, respectively. Both compounds decreased also the number of cell divisions. Mitotic indices of the cells submitted to these compounds were: 96/2000 and 48/1000, respectively, in comparison with control (169/2000). It seems that the antimitotic action of the compounds may be associated with their antiviral activity. Moreover, isolactarorufin 8-[N-acetyl-(2′R,3′S)-3′-phenylisoserinate] inhibited PHA-induced T lymphocyte proliferation.

Abbreviations

MEM:minimum essential medium

FCS:foetal calf serum

MTT:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide

CC₅₀:50 % cytotoxic concentration

HSV-1_MC:Herpes simplex virus 1 McIntyre strain

TCID₅₀:50 % tissue culture infective dose

CPE:cytopathic effect

IC₅₀:50 % inhibitory concentration

PBMCs:peripheral blood mononuclear cells

PHA:phytohemagglutinin

Key words

Lactarius - Russulaceae - sesquiterpenes - paclitaxel - antiviral activity - lymphocyte proliferation - mitosis

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