ABSTRACT
The synthesis and X-ray diffraction established the structure of (7R,8S)-(see text for symbol)-(13R,17R)-trioxolaneabietic acid. Predicted by the computer system PASS antineoplastic activity and the ability to induce apoptosis, a mechanism of cell death, is correlated with experimentally shown cytotoxic activity against malignant cell line MeWo. Results of tests on animals have shown that abietic acid and its 9R,11S-epoxy-12R,15R-trioxolane derivative have anti-inflammatory and antiulcer activity in the absence of adverse effects on animal organisms.
Subject(s)
Abietanes/chemical synthesis , Abietanes/pharmacology , Abietanes/chemistry , Acetic Acid/toxicity , Animals , Cell Line, Tumor/drug effects , Formaldehyde/toxicity , Humans , Inflammation/chemically induced , Inflammation/drug therapy , Magnetic Resonance Spectroscopy , Mice , Rats , Ulcer/chemically induced , Ulcer/drug therapy , Ulcer/pathology , X-Ray DiffractionABSTRACT
Under the action of PCl(5), the Beckman rearrangement of a 3 : 1 mixture of Z- and E-ketoximes of 18beta-hydroxydihydroquinopimaric acid resulted in 5'-caprolactam and isomeric caprolactams containing fragments of cyclic ether. Z- and E-ketoximes were separated as acetates. Using a carrageenan inflammation model, we demonstrated that the anti-inflammatory activity of quinopimaric acid derivatives was comparable with that of diclofenac.
Subject(s)
Abietanes/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Abietanes/chemistry , Abietanes/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antiviral Agents/chemical synthesis , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Carrageenan , Edema/chemically induced , Edema/drug therapy , Influenza A virus/drug effects , Mice , Stereoisomerism , Structure-Activity Relationship , Toxicity Tests, AcuteABSTRACT
The synthesis of a new group of maleopimaric acid amides containing fragments of the methyl esters of amino acids, aliphatic amines, imidazole and N-methylpiperazine was carried out. Ozonolysis of methyl maleopimarate flows through the cleavage of double bond C18(19) and the disclosure of anhydrous cycle with formation of secotriacid. As a result of screening of anti-inflammatory and antiulcer activity of maleopimaric acid derivatives new effective compounds such as methyl esters of maleopimaric acid and product of ozonolysis - diterpenic secotriacid, maleopimaric acid amide with L-leucine were revealed. An important advantage of the compounds studied is the low toxicity and the presence of bidirectional activity in the absence of adverse effects on the animal.
Subject(s)
Amides/chemical synthesis , Ozone/chemistry , Triterpenes/chemistry , Amides/chemistry , Molecular StructureABSTRACT
Synthesis of dihydroquinopymaric acid amides and their 2beta-succinyl and 2beta-phthalyl derivatives containing residues of amino acids was carried out for the first time. Antiviral properties of the compounds synthesized were investigated.
Subject(s)
Abietanes/chemistry , Amino Acids/chemistry , Antiviral Agents/chemistry , Abietanes/pharmacology , Amino Acids/pharmacology , Animals , Antiviral Agents/pharmacology , Cells, Cultured , Chick Embryo , Influenza A Virus, H7N7 Subtype/drug effectsABSTRACT
Betulonic acid amides with aliphatic and heterocyclic amines and with L-amino acids were synthesized by the acid chloride method. Betulonic acid amide and L-methionine derivatives of betulonic acid and its 3-oxime effectively inhibit the influenza A virus. Betulonic acid octadecylamide is active against the herpes simplex type 1 virus. The conjugate of betulonic acid 3-oxime with L-methionine is also active toward HIV-1. The tested compounds mainly show no activity toward the ECHO6 virus, which is devoid of a coat. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 1; see also http://www.maik.ru.
Subject(s)
Amides/chemistry , Amino Acids/chemistry , Antiviral Agents/chemical synthesis , Antiviral Agents/pharmacology , Oleanolic Acid/analogs & derivatives , Oleanolic Acid/chemistry , Animals , Cells, Cultured , Chick Embryo , HIV-1/drug effects , Herpesvirus 1, Human/drug effects , Magnetic Resonance Spectroscopy , Spectrophotometry, InfraredABSTRACT
Ureides and carbamates of betulinic acid and its derivatives were prepared in good yields by interaction of betulinic acid, betulonic acid, and betulonic acid 3-oxime with amines, amino acids, and alcohols. Ureides of betulonic acid containing L-Val and L-Met residues were found to be effective against herpes simplex type 1 virus. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2003, vol. 29, no. 6; see also http://www.maik.ru.
