Design and synthesis of pentacyclic triterpene conjugates and their use in medicinal research

被引:88
作者
Hodon, Jiri [1 ]
Borkova, Lucie [1 ]
Pokorny, Jan [1 ]
Kazakova, Anna [1 ]
Urban, Milan [2 ]
机构
[1] Palacky Univ, Fac Sci, Dept Organ Chem, 17 Listopadu 1192-12, Olomouc 77146, Czech Republic
[2] Palacky Univ, Fac Med & Dent, Inst Mol & Translat Med, Hnevotinska 5, Olomouc 77900, Czech Republic
关键词
Triterpenoid; Conjugate; Target; Mechanism of action; Synthesis; Cytotoxicity; HIV; Antiviral; Leishmania; Theranostics; Fluorescence; Mitochondria; Biological activity; BETULINIC ACID-DERIVATIVES; IMMUNODEFICIENCY-VIRUS TYPE-1; LABELED GLYCYRRHETINIC ACID; HUMAN SERUM-ALBUMIN; URSOLIC ACID; OLEANOLIC ACID; BIOLOGICAL EVALUATION; MATURATION INHIBITOR; LUPANE TRITERPENOIDS; RHODAMINE-B;
D O I
10.1016/j.ejmech.2019.111653
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Triterpenoids are natural products from plants and many other organisms that have various biological activities, such as antitumor, antiviral, antimicrobial, and protective activities. This review covers the synthesis and biological evaluation of pentacyclic triterpene (PT) conjugates with other molecules that have been found to increase the IC50 or improve the pharmacological profile of the parent PT. Some of these molecules are designed to target specific proteins or cellular organelles, which has resulted in highly selective lead structures for drug development. Other PT conjugates are useful for investigating their mechanism of action. This concept has been very successful: 1) Many compounds, especially mitochondria-targeting PT conjugates, have reached a selective cytotoxicity at low nanomolar concentrations in cancer cells. 2) A number of PT conjugates have had high activity against HIV or the influenza virus. 3) Fluorescent PT conjugates have been able to visualize the FT in living cells, which has allowed quantification of the uptake and distribution of the PT within the cell. 4) Biotinylated PT conjugates have been used to identify target proteins, which may help to show their mechanism of action. 5) A large number of PT conjugates with polyethylene glycol (PEG), polyamines, etc. form nanometer-sized micelles that have a much better pharmacological profile than the PT alone. In summary, the connection of a PT to an appropriate modifying molecule has resulted in extremely useful semisynthetic compounds with a high potential to treat cancer or viral infections or compounds that are useful for the study of the mechanism of action of PTs at the molecular level. (C) 2019 Elsevier Masson SAS. All rights reserved.
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页数:25
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