Betulinic acids are lupine-type pentacyclic triterpenoid saponins commonly found in some plants of Betulaceae family, especially in the bark of betula alba (birch). The potent anti-HIV and anti-tumor activities of betulinic acids have been greatly concerned. The natural betulinic acids include betulinic acid, 23-hydroxy betulinic acid, betulin and so on. Some investigations on the structural modifications of betulinic acids were carried out, and many derivatives with excellent biological activity have been obtained nowadays. In this paper, the research advances of the structural modification of betulinic acids, as well as their anti-HIV and anti-tumor activities are reviewed.
Anti-HIV Agents ; chemical synthesis ; chemistry ; isolation & purification ; pharmacology ; Antineoplastic Agents, Phytogenic ; chemical synthesis ; chemistry ; isolation & purification ; pharmacology ; Betula ; chemistry ; Cell Line, Tumor ; HIV ; drug effects ; Humans ; Plant Bark ; chemistry ; Plant Leaves ; chemistry ; Plants, Medicinal ; chemistry ; Triterpenes ; chemical synthesis ; chemistry ; isolation & purification ; pharmacology ; therapeutic use

The constrained alpha-helical structure of a C-peptide is useful for enhancing anti-HIV-1 activity. The i and i+3 positions in an alpha-helical structure are located close together, therefore D-Cys (dC) and L-Cys (C) were introduced at the positions, respectively, to make a dC-C disulfide bond in 28mer C-peptides. Accordingly, this study tested whether a dC-C disulfide bond would increase the alpha-helicity and anti-HIV-1 activity of peptides. A C-peptide can be divided into three domains, the N-terminal hydrophobic domain (HPD), middle interface domain (IFD), and C-terminal hydrogen domain (HGD), based on the binding property with an N-peptide. In general, the dC-C modifications in HPD enhanced the anti-HIV-1 activity, while those in IFD and HGD resulted in no or much less activity. The modified peptides with no activity clearly showed much less alpha-helicity than the native peptides, while those with higher activity showed an almost similar or slightly increased alpha-helicity. Therefore, the present results suggest that the introduction of a dC-C bridge in the N-terminal hydrophobic domain of a C-peptide may be useful for enhancing the anti-HIV-1 activity.
Amino Acid Sequence ; Anti-HIV Agents/chemical synthesis/*chemistry/isolation & purification/*pharmacology ; Cell Line ; Circular Dichroism ; Cysteine/chemistry ; Disulfides/chemistry ; HIV Envelope Protein gp41/*chemistry ; HIV-1/*drug effects/growth & development ; Humans ; Inhibitory Concentration 50 ; Models, Molecular ; Molecular Sequence Data ; Peptides/chemical synthesis/*chemistry/isolation & purification/*pharmacology ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Research Support, Non-U.S. Gov't ; Structure-Activity Relationship

Resveratrol, isorhapontigenin and pinosylvin, isolated from Gnetum parvifolium, and their analogues have been synthesized and tested for their inhibitory activity of HIV-1. Natural product 12a and analogues (12d, 12e, 12g) display significant inhibitory activity of HIV-1 replication. Among them, compound 12d (trans-3, 4, 5, 4'-tetrahydroxystilbene) exhibits the most potent anti-HIV-1 activity with an IC50 value of 1.84 micromol x L(-1).
Anti-HIV Agents ; isolation & purification ; pharmacology ; Cells, Cultured ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Gnetum ; chemistry ; HIV-1 ; drug effects ; physiology ; Inhibitory Concentration 50 ; Leukocytes, Mononuclear ; cytology ; virology ; Molecular Structure ; Plants, Medicinal ; chemistry ; Stilbenes ; chemical synthesis ; chemistry ; isolation & purification ; pharmacology ; Virus Replication ; drug effects