ABSTRACT
The optimal conditions for C3 oxidative biotransformation of 1.0 g/L pentacyclic triterpenoids oleanolic (OA) and glycyrrhetinic (GA) acids were determined using the resting cells of Rhodococcus rhodochrous IEGM 1360 from the Regional Specialised Collection of Alkanotrophic Microorganisms. Resting cell suspensions (OD600 2.6, pH 8.0, and OD600 2.2, pH 6.0) showed the highest catalytic activity against OA and GA, resulting in the formation of 61 and 100% of their 3-oxo derivatives, respectively. Using phase contrast, atomic force, and confocal laser scanning microscopy, an adaptive response of rhodococci to the effects of OA and GA was revealed. In silico, the apoptotic activity of 3-oxo-OA and antioxidant activity of 3-oxo-GA have been assumed. In vitro, a pronounced antibacterial activity of 3-oxo-OA against Micrococcus luteus, Escherichia coli, Staphylococcus aureus, and Bacillus subtilis was shown. The absence of toxic effects of the above triterpenoids and their 3-oxo derivatives on aquatic objects and plants was demonstrated in silico and in vitro, respectively. Supplementary Information: The online version contains supplementary material available at 10.1134/S0026261722603360.
ABSTRACT
Four types of amide (C3; C28; C3-C28) conjugates based on 2,3-seco-18alphaH-oleanane and 2,3-secolupane mono- and dicarboxylic acids were synthesized. The range of diamide derivatives was supplemented with C3-C3' and C28-C28' dicondensed amides with two A-secotriterpene backbones educed by reacting monocarboxylic A-secoacids with biogenic amino acid lysine. Compounds with inhibitory action against herpes virus reproduction (EC50 8.7 and 4.1 McM) were found among the synthesized mono- and diamide derivatives containing an ethyl-beta-alaninate fragment. It has been ascertained that diamide with ethyl-beta-alaninate fragment combines anti-herpes virus properties and anti-HIV activity (EC50 5.1 McM). For active compounds, the maximum non-toxic concentration (MNTC)/EC50 ratios ranges from 9.7 to 40.8. The synthesized amide conjugates do not exhibit any marked cytotoxic effects against human tumor cell lines rabdomiosarcoma RD TE32, A549 lung carcinoma and melanoma MS.
Subject(s)
Amides/chemical synthesis , Antineoplastic Agents/chemical synthesis , Antiviral Agents/chemistry , Oleanolic Acid/analogs & derivatives , Triterpenes/chemistry , Amides/chemistry , Amides/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antiviral Agents/chemical synthesis , Antiviral Agents/pharmacology , Cell Line, Tumor , HIV-1/drug effects , Humans , Oleanolic Acid/chemical synthesis , Oleanolic Acid/chemistry , Oleanolic Acid/pharmacology , Simplexvirus/drug effects , Triterpenes/chemical synthesis , Triterpenes/pharmacology , Virus Replication/drug effectsABSTRACT
Water-soluble sulfate polysalts of carboxymethyl cellulose and tertiary aminomethyl derivatives of 2-isobornyl-4-methylphenol was obtained. For the synthesized conjugates investigated in vivo anti-inflammatory activity in the test of acute formalin inflammation and analgesic activity in tests the "hot plate" and "vinegar cramps".
Subject(s)
Carboxymethylcellulose Sodium , Inflammation , Pain Measurement/drug effects , Pain , Animals , Carboxymethylcellulose Sodium/analogs & derivatives , Carboxymethylcellulose Sodium/chemical synthesis , Carboxymethylcellulose Sodium/chemistry , Carboxymethylcellulose Sodium/pharmacology , Formaldehyde/toxicity , Inflammation/chemically induced , Inflammation/drug therapy , Mice , Pain/drug therapy , Pain/pathology , Solubility , Sulfates/chemical synthesis , Sulfates/chemistry , Sulfates/pharmacology , Water/chemistryABSTRACT
The conditions for a directed biocatalytic oxidation of beta-sitosterol to a pharmacologically promising stigmast-4-en-3-one using Rhodococcus actinobacteria were selected. It was shown that palmitic acid induced the cholesterol oxidase reaction and allowed for the decrease in the bioconversion process duration from 7 to 5 days. The maximum level ofstigmast-4-ene-3-one formation was achieved using n-hexadecane as an additional growth substrate. With increased concentrations of beta-sitosterol (up to 2 g/L) an effective target product formation (80%) was achieved in the presence of Tween-80 and beta-cyclodextrine. R. erythropolis strains were 1.5-2 times more active than R. ruber strains in catalyzing the beta-sitosterol biotransformation process.
Subject(s)
Biocatalysis , Rhodococcus/metabolism , Sitosterols/metabolism , Stigmasterol/analogs & derivatives , Alkanes/chemistry , Biotransformation , Cholesterol Oxidase/chemistry , Cholesterol Oxidase/metabolism , Sitosterols/chemistry , Stigmasterol/chemical synthesisABSTRACT
Novel hydrazones of lupane and 19beta,28-epoxy-18alpha-oleanane type have been synthesized via interaction of 2,3-secotriterpenic aldehydonitriles with substituted hydrazines. As a result of investigation of 2,3-secotriterpenic hydrazones antiviral activity to the strain "Indiana" of vesicular stomatitis virus on two models of mammal's line cell infection, acetylhydrazone 1-cyano-2,3-seco-19beta,28-epoxy-18alpha-olean-3-al has been found to have a high prophylactic activity 0.00016 microg/ml to vesicular stomatitis virus and to inhibit a virus reproduction in primarily infected cells in 0.21 microg/ml concentration.
Subject(s)
Antiviral Agents , Hydrazones , Oleanolic Acid , Rhabdoviridae Infections/drug therapy , Triterpenes , Vesicular stomatitis Indiana virus , Animals , Antiviral Agents/chemical synthesis , Antiviral Agents/pharmacology , Cell Line , Hydrazones/chemical synthesis , Hydrazones/pharmacology , Oleanolic Acid/analogs & derivatives , Oleanolic Acid/chemical synthesis , Oleanolic Acid/pharmacology , Swine , Triterpenes/chemical synthesis , Triterpenes/pharmacologyABSTRACT
Novel 2,3-seco-triterpenic amides were prepared by the interaction of the chloride of 2,3-seco-l-cyano-19beta,28-epoxy-18alpha-oleane-3-oic acid with primary amines and synthetic and biogenic amino acids. A cytotoxic triterpenic conjugate with a residue of the ethyl ester of beta-alanine was found among the synthesized nitrogen-containing derivatives. Treatment with this conjugate in a concentration of 100 muM resulted in the 45.5% survival of melanoma cells in the medium.
Subject(s)
Amides/chemical synthesis , Antineoplastic Agents/chemical synthesis , Epoxy Compounds/chemical synthesis , Triterpenes/chemical synthesis , Amides/chemistry , Amides/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Drug Screening Assays, Antitumor , Epoxy Compounds/chemistry , Epoxy Compounds/pharmacology , Humans , Triterpenes/chemistry , Triterpenes/pharmacologyABSTRACT
The immunotropic effect of the 2,3-seco derivatives of allobetulon, betulonic acid, and the methyl ester of betulonic acid were studied. It was found that the highest activity is shown by compounds with an oleanane fragment. The presence of a free C28-carboxyl group enhances the activity of lupeolic 2,3-seco derivatives. A significant contribution to the development of the immune response is introduced by a functional group at the C3 atom in the A ring - the C3-carboxy derivatives intensify the processes of antibody production and alter the number and ratio of leukocyte forms. It is shown that 2,3-seco-1-cyano-19beta,28-epoxy-18alpha-olean-3-oic acid stimulates humoral immunity with a positive influence on hematopoiesis.
Subject(s)
Immunologic Factors/pharmacology , Triterpenes/pharmacology , Animals , Antibody Formation/drug effects , Female , Immunity, Humoral/drug effects , Immunologic Factors/chemical synthesis , Immunologic Factors/chemistry , Mice , Oleanolic Acid/chemical synthesis , Oleanolic Acid/chemistry , Oleanolic Acid/pharmacology , Structure-Activity Relationship , Triterpenes/chemical synthesis , Triterpenes/chemistryABSTRACT
Comparative study of sulfoxidation activity of free and immobilized Rhodococcus rhodochrous IEGM 66 cells was performed. Free Rhodococcus cells (in the presence of 0.1 vol % n-hexadecane) displayed maximal oxidative activity towards thioanisole (0.5 g/l), a prochiral organic sulfide, added after 48-h cultivation of bacterial cells. Higher sulfide concentrations inhibited sulfoxidation activity of Rhodococcus. Use of immobilized cells allowed the 2-day preparatory stage to be omitted and a complete thioanisole bioconversion to be achieved in 24 h in the case that biocatalyst and 0.5 g/l thioanisole were added simultaneously. The biocatalyst immobilized on gel provides for complete thioanisole transformation into (S)-thioanisole sulfoxide (optical purity of 82.1%) at high (1.0-1.5 g/l) concentrations of sulfide substrate.
Subject(s)
Rhodococcus/metabolism , Sulfides/metabolism , Alkanes , Biocatalysis , Biotechnology/methods , Biotransformation , Cells, Immobilized/metabolism , Oxidation-Reduction , Rhodococcus/growth & developmentABSTRACT
New lupane beta-enaminoketones were synthesized by interaction of methyl 2-hydroxymethylene-3-oxolup-20(29)-en-28-oate with aliphatic amines. Immunotropic activity was found for some of these compounds.
Subject(s)
Immunosuppressive Agents/chemical synthesis , Triterpenes/chemical synthesis , Animals , Antibody Formation , Esters , Immunity, Cellular , Immunosuppressive Agents/chemistry , Immunosuppressive Agents/immunology , Ketones/chemical synthesis , Ketones/immunology , Magnetic Resonance Spectroscopy , Male , Mice , Spectrophotometry, Infrared , Structure-Activity Relationship , Triterpenes/chemistry , Triterpenes/immunologyABSTRACT
2-Alkylaminomethylene-19beta,28-epoxyolean-3-ones were obtained by interaction of 2-hydroxymethylene-19beta,28-epoxyolean-3-one with aliphatic amines. Some of the resulting substances exhibit immunotropic activity.
Subject(s)
Oleanolic Acid/chemical synthesis , Oleanolic Acid/immunology , Terpenes/chemical synthesis , Terpenes/immunology , Amines/chemistry , Amines/immunology , Animals , Male , Mice , Oleanolic Acid/analogs & derivatives , Oleanolic Acid/chemistry , Oleanolic Acid/pharmacology , Terpenes/chemistry , Terpenes/pharmacologyABSTRACT
The ability of pure cultures of Rhodococcus actinobacteria from the Ural specialized collection of alkanotrophic microorganisms (World Federation for Culture Collections accession number 768; http://www.ecology.psu.ru/iegmcol) to convert beta-sitosterol (BSS) and its 3beta-acylated derivatives was studied. Rhodococcus strains with pronounced cholesterol oxidase activity, capable of converting BSS to stigmat-4-ene-3-one in the reaction of cooxidation with n-hexadecane, were selected. The dependence of the activity of cholesterol oxidase of rhodococci on the length of the acyl group in BSS esters was studied. Conditions under which Rhodococcus cells convert BSS to 17beta-hydroxyandrost-4-ene-3-one (testosterone), commonly used in pharmacology, were determined.