ABSTRACT
A series of dimeric procyanidins (1-9) and some related polyphenols (10-15) were chosen as model compounds in a comparative investigation for various biological activities in order to obtain structure-activity relationships. Antiviral [herpes simplex virus (HSV) and human immunodeficiency virus (HIV)], antibacterial, superoxide radical-scavenging, and complement-modulating properties were assessed. In general, more pronounced activities were seen with epicatechin-containing dimers for anti-HSV, anti-HIV, and radical-scavenging effects, while the presence of ortho-trihydroxyl groups in the B-ring was important in compounds exhibiting anti-HSV and radical-scavenging effects and complement classical pathway inhibition. Double interflavan linkages gave rise to interesting antiviral effects (HSV and HIV) and complement inhibition. The influence of the degree of polymerization or the type of interflavan linkage (4-->6 or 4-->8) differed in the different biological systems evaluated. Only minor or moderate antibacterial effects were observed for the compounds under investigation.
Subject(s)
Anthocyanins/pharmacology , Anti-Infective Agents/pharmacology , Antiviral Agents/pharmacology , Complement Inactivator Proteins/pharmacology , Flavonoids , Free Radical Scavengers/pharmacology , Phenols/pharmacology , Plants, Medicinal/chemistry , Polymers/pharmacology , Anthocyanins/chemistry , Anthocyanins/isolation & purification , Anti-Bacterial Agents , Anti-HIV Agents/pharmacology , Bacteria/drug effects , Euphorbiaceae/chemistry , Hemolysis/drug effects , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Peru , Simplexvirus/drug effectsABSTRACT
In attempts to detect inhibitors of infectious pancreatic necrosis virus (IPNV) replication, we have evaluated, by an IPNV plaque inhibition assay, a group of compounds that have broad spectrum antiviral activity for both single- and double-stranded RNA viruses. The inosine monophosphate dehydrogenase (IMP dehydrogenase) inhibitors 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (ribavirin) and 5-ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide (EICAR), and the orotidine monophosphate decarboxylase (OMP decarboxylase) inhibitor 4-hydroxy-3-beta-D-ribofuranosylpyrazole-5-carboxamide (pyrazofurin), were found to inhibit IPNV replication. For EICAR and pyrazofurin the concentrations that inhibited the IPNV plaque formation by 50% (EC50) were 0.01 micrograms/ml and 0.5 micrograms/ml, respectively. The cytotoxic concentrations required to reduce cell viability by 50% (CC50) were 50 micrograms/ml and 100 micrograms/ml, respectively, and the concentrations that reduced [methyl-3H] thymidine incorporation by 50% (IC50) were 0.5-1 and 50 micrograms/ml. Thus, for both compounds the IPNV-inhibitory concentration was 50-100 times lower than the concentration that affected DNA synthesis in growing cells. EICAR and pyrazofurin seem to be good candidates for further evaluation in an in vivo model of IPNV infection.
Subject(s)
Antiviral Agents/pharmacology , Hydrolases/antagonists & inhibitors , IMP Dehydrogenase/antagonists & inhibitors , Infectious pancreatic necrosis virus/drug effects , Adenosine/analogs & derivatives , Adenosine/pharmacology , Adenosylhomocysteinase , Amides , Animals , Cell Line , DNA/drug effects , Foscarnet/pharmacology , Infectious pancreatic necrosis virus/growth & development , Infectious pancreatic necrosis virus/physiology , Orotidine-5'-Phosphate Decarboxylase/antagonists & inhibitors , Pyrazoles , Ribavirin/pharmacology , Ribonucleosides/pharmacology , Ribose , Salmon , Viral Plaque Assay , Virus Replication/drug effectsABSTRACT
Three SAH hydrolase inhibitors, (RS)-3-adenin-9-yl-2-hydroxypropanoic acid (isobutyl ester) [(RS)-AHPA]; (RS)-9-(2,3-dihydroxypropyl)adenine [(RS)-DHPA] and the carbocyclic analog of 3-deazaadenosine (C-c3Ado) were evaluated for their inhibitory activity against tobacco mosaic virus (TMV) and potato virus X (PVX). Using the local lesion assay and ELISA, we demonstrated that all three compounds inhibit the replication of TMV and PVX. Whereas the three compounds proved about equally active against PVX, (RS)-AHPA was the most effective against TMV. (RS)-AHPA and C-c3Ado induced chlorosis in Nicotiana tabacum leaf discs. They also caused a substantial reduction in the growth of the main root of Phaseolus vulgaris. (RS)-DHPA was less phytotoxic than its two congeners.
Subject(s)
Adenine/analogs & derivatives , Antiviral Agents/pharmacology , Hydrolases/antagonists & inhibitors , Phenylbutyrates/pharmacology , Plant Viruses/drug effects , Virus Replication/drug effects , Adenine/pharmacology , Adenosylhomocysteinase , Animals , Enzyme-Linked Immunosorbent Assay , Plant Diseases , Plant Viruses/enzymology , Plant Viruses/growth & development , Rabbits , Tobacco Mosaic Virus/drug effects , Tobacco Mosaic Virus/enzymology , Tobacco Mosaic Virus/growth & developmentABSTRACT
Two established antiviral agents, dihydroxypropyladenine (RS)-DHPA and bromovinyldeoxyuridine (BVDU) were evaluated for their inhibitory effects on 4 plant viruses: Tobacco mosaic virus, potato virus X (PVX), eggplant mosaic virus (EMV) and a potyvirus isolated from Solanum palinacanthum (Poty-Sp). Using the leaf disc incubation test, BVDU proved virtually inactive while (RS)-DHPA efficiently inhibited EMV and Poty-Sp when applied at concentrations as low as 5 mg/l. TMV was less susceptible to the chemical while PVX could be inhibited at drug concentrations of 100 mg/l. To achieve a similar inhibitory effect in the leaf spray test, concentrations up to 250 and 500 mg/l were required. Using these tests no phytotoxicity was observed with (RS)-DHPA at any of the concentrations used.