M. P. Polovinka

Anti-viral activity of (−)- and (+)-usnic acids and their derivatives against influenza virus A(H1N1)2009

Influenza is a widespread respiratory infection. Every year it causes epidemics, quickly spreading from country to country, or even pandemics, involving a significant part of the human population of the earth. Being a highly variable infection, influenza easy accumulates the resistance mutations to many antivirals. Usnic acid, a dibenzofuran originally isolated from lichens belongs to the secondary metabolites and has a broad spectrum of biological activity. In humans, it can act as an anti-inflammatory, antimitotic, antineoplasic, antibacterial, and antimycotic agent. In this work we studied for the first time the antiviral activity of usnic acid and its derivatives against the pandemic influenza virus A(H1N1)pdm09. A total of 26 compounds representing (+) and (-) isomers of usnic acid and their derivates were tested for cytotoxicity and anti-viral activity in MDCK cells by microtetrazolium test and virus yield assay, respectively. Based on the results obtained, 50% cytotoxic dose (CTD(50)) and 50% effective dose (ED(50)) and selectivity index (SI) were calculated for each compound. Eleven of them were found to have SI higher than 10 (highest value 37.3). Absolute configuration was shown to have critical significance for the anti-viral activity. With minor exceptions, in the pair of enantiomers, (-)-usnic acid was more active comparing to (+)-isomer, but its biological activity was reversed after the usnic acid was chemically modified. Based on the obtained results, derivatives of usnic acid should be considered as prospective compounds for further optimization as anti-influenza substances.

Low-molecular-weight phenolic compounds from Hedysarum theinum roots

Isoflavonoids (−)-medicarpin, (−)-vestitol, formononetin, 8-hydroxydaidzein, and 6″-O-acetylononin were isolated for the first time in addition to (−)-catechin, (−)-epicatechin, protocatechoic acid, raspberry ketone, and rhododendrol from the alcohol extract of Hedysarum theinum roots.

Chemical modification of usnic acid: III.* Reaction of (+)-usnic acid with substituted phenylhydrazines

Reactions of (+)-usnic acid with a number of substituted (halo, alkyl, alkoxy, nitro) phenylhydrazines led to the formation of the corresponding benzofuro[3,2-f]indazole derivatives or hydrazones at the acetyl group on C2, depending on the initial hydrazine.

Amino-derivatives of usninic acid

Products from the reaction of usninic acid and 4-(3-aminopropyl)-2,6-di-t-butylphenol, 4-(2-aminoethyl)-2,6-di-t-butylphenol, antipyrine, N,N-diethylaminoethylamine, p-chloroaniline, and p-bromoaniline in addition to the quaternary ammonium salt (E)-2-(1-(6-acetyl-7,9-dihydroxy-8,9b-dimethyl-1,3-dioxo-1,9b-dihydrodibenzo[b,d]furan-2(3H)-ylidene)ethylamino)-N,N-diethyl-N-methylethaneammonium iodide were obtained.

Fatty-acid composition and secondary metabolites from slightly polar extracts of the aerial part of Primula macrocalyx

Flavones 2′,5′-dimethoxyflavone, 3′-methoxy-4′,5′-methylenedioxyflavone, 3′,4′-dimethoxyflavone, 5,6,2′,3′,6′-pentamethoxyflavone, and 5,6,2′,3′,5′,6′-hexamethoxyflavone; salicylates, methyl-4-methoxysalicylate and peonol; and bisbibenzyl polyphenol riccardin C were isolated for the first time from the acetone extract of the aerial part of Primula macrocalyx Bge. The content of free and total fatty acids was determined by GC and GC—MS. Palmitic (16:0), octadecatetraenoic 18:4 (6,9,12,15), linoleic 18:2 (9,12), and α-linolenic 18:3 (9,12,15) were the principal acids from the aerial part of Primula macrocalyx.

Transformations of 6,7-Epoxy Derivatives of Citral and Citronellal in Various Acidic Media

The transformations of 6,7-epoxy derivatives of widely spread in the nature unsaturated aldehydes, citral and citronellal, in various acidic media both under conditions of homogeneous and heterogeneous catalysis were investigated. A number of previously unknown products belonging to different classes of organic compounds was obtained. Probable mechanisms of the products formation are discussed.

Oxidation of usninic acid

Reactions of usninic acid with various oxidants were studied. The oxidation occurred at the resorcinol ring. New derivatives of usninic acid were obtained from reactions with per-acids.

Secondary metabolites of the lichen Cladonia stellaris

The composition of slightly polar extracts of the lichen Cladonia stellaris (Opiz.) was studied. The major metabolites of the CHCl3 and Me2CO extracts were isolated. Lichen acids 6 and 7 in addition to 3–5, derivatives of olivetolcarboxylic acid (7), were isolated for the first time from the lichen C. stellaris. The CHCl3 extract was tested for antagonist activity against pathogens of the principal agricultural diseases.

Reduction of (+)-usninic acid and its pyrazole derivative by sodium borohydride

The reaction of (+)-usninic acid and its pyrazole derivative with sodium borohydride was studied. The reduction occurred stereoselectively at the endocyclic carbonyl group. Novel (+)-usninic acid derivatives that were reduction products of the carbonyls were obtained.

Structure of oligomeric proanthocyanidines from Hedysarum thienum roots studied by thiolysis and MALDI-TOF MS

Oligomeric proanthocyanidines from Hedysarum theinum roots that were cleaved by benzylmercaptan were shown to be heterogeneous mixtures consisting of prodelphinine and procyanidine structural units with the former dominating. Fractionation of oligomeric proanthocyanidines on polyamide and MCI gel CHP20P sorbent isolated fractions containing primarily mixtures of di- and trimeric, tri- and tetrameric, or tetra- and pentameric proanthocyanidines. Analysis by mass spectrometry (MALDI-TOF) showed that fractions of trimers and tetramers contained more proanthocyanidines with a single A-type bond than fractions of dimers and trimers.