Recent Developments in the Functionalization of Betulinic Acid and Its Natural Analogues: A Route to New Bioactive Compounds

被引：78

作者：

Sousa, Joana L. C. ^{[1
,2
,3
]}

Freire, Carmen S. R. ^{[3
]}

Silvestre, Armando J. D. ^{[3
]}

Silva, Artur M. S. ^{[1
,2
]}

机构：

[1] Univ Aveiro, Dept Chem, QOPNA, P-3810193 Aveiro, Portugal

[2] Univ Aveiro, Dept Chem, LAQV REQUIMTE, P-3810193 Aveiro, Portugal

[3] Univ Aveiro, Dept Chem, CICECO, P-3810193 Aveiro, Portugal

来源：

MOLECULES | 2019年 / 24卷 / 02期

关键词：

triterpenes; betulinic acid; betulin; betulonic acid; 23-hydroxybetulinic acid; synthesis; functionalization; derivatization; PENTACYCLIC TRITERPENE DERIVATIVES; BIOLOGICAL EVALUATION; ANTITUMOR-ACTIVITY; LUPANE TRITERPENOIDS; CYTOTOXIC EVALUATION; IN-VITRO; MATURATION INHIBITOR; DESIGN; ESTERS; HYBRIDS;

D O I：

10.3390/molecules24020355

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Betulinic acid (BA) and its natural analogues betulin (BN), betulonic (BoA), and 23-hydroxybetulinic (HBA) acids are lupane-type pentacyclic triterpenoids. They are present in many plants and display important biological activities. This review focuses on the chemical transformations used to functionalize BA/BN/BoA/HBA in order to obtain new derivatives with improved biological activity, covering the period since 2013 to 2018. It is divided by the main chemical transformations reported in the literature, including amination, esterification, alkylation, sulfonation, copper(I)-catalyzed alkyne-azide cycloaddition, palladium-catalyzed cross-coupling, hydroxylation, and aldol condensation reactions. In addition, the synthesis of heterocycle-fused BA/HBA derivatives and polymerBA conjugates are also addressed. The new derivatives are mainly used as antitumor agents, but there are other biological applications such as antimalarial activity, drug delivery, bioimaging, among others.

引用

页数：35

共 95 条

[1] Cytotoxic profiling of artesunic and betulinic acids and their synthetic hybrid compound on neurons and gliomas [J].

Ackermann, Annemarie ;

Karagoez, Aysun Capci ;

Ghoochani, Ali ;

Buchfelder, Michael ;

Eyuepoglu, Ilker ;

Tsogoeva, Svetlana B. ;

Savaskan, Nicolai .

ONCOTARGET, 2017, 8 (37) :61457-61474

[2] Pharmacological properties of the ubiquitous natural product betulin [J].

Alakurtti, Sami ;

Makela, Taru ;

Koskimies, Salme ;

Yli-Kauhaluoma, J. .

EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 2006, 29 (01) :1-13

[3]

Ali MTM, 2017, ORIENT J CHEM, V33, P242, DOI 10.13005/ojc/330128

[4] Betulinic Acid: Recent Advances in Chemical Modifications, Effective Delivery, and Molecular Mechanisms of a Promising Anticancer Therapy [J].

Ali-Seyed, Mohamed ;

Jantan, Ibrahim ;

Vijayaraghavan, Kavitha ;

Bukhari, Syed Nasir Abbas .

CHEMICAL BIOLOGY & DRUG DESIGN, 2016, 87 (04) :517-536

[5] New hybrids between triterpenoid acids and nucleoside HIV-RT inhibitors [J].

Anh Thi Tuyet Dang ;

Chinh The Pham ;

Than Anh Le ;

Hieu Hong Truong ;

Ha Thu Thi Vu ;

Soldatenkov, Anatoly T. ;

Tuyen Van Nguyen .

MENDELEEV COMMUNICATIONS, 2015, 25 (02) :96-98

[6] Synthesis and Cytotoxic Activity of Lupane Triterpenoids Containing 1,3,4-Oxadiazoles [J].

Antimonova, A. N. ;

Petrenko, N. I. ;

Shakirov, M. M. ;

Pokrovskii, M. A. ;

Pokrovskii, A. G. ;

Shul'ts, E. E. .

CHEMISTRY OF NATURAL COMPOUNDS, 2014, 50 (06) :1016-1023

[7] Synthesis of 19-(2,6-Dimethylpyrid-4-yl)-20,29,30-trinorlupanes [J].

Antimonova, A. N. ;

Petrenko, N. I. ;

Shakirov, M. M. ;

Shul'ts, E. E. .

CHEMISTRY OF NATURAL COMPOUNDS, 2014, 50 (02) :305-310

[8] Synthesis and study of mutagenic properties of lupane triterpenoids containing 1,2,3-triazole fragments in the C-30 position [J].

Antimonova, A. N. ;

Petrenko, N. I. ;

Shakirov, M. M. ;

Rybalova, T. V. ;

Frolova, T. S. ;

Shul'ts, E. E. ;

Kukina, T. P. ;

Sinitsyna, O. I. ;

Tolstikov, G. A. .

CHEMISTRY OF NATURAL COMPOUNDS, 2013, 49 (04) :657-664

[9] Novel triazoles of 3-acetylbetulin and betulone as anticancer agents [J].

Bebenek, Ewa ;

Kadela-Tomanek, Monika ;

Chrobak, Elwira ;

Latocha, Malgorzata ;

Boryczka, Stanislaw .

MEDICINAL CHEMISTRY RESEARCH, 2018, 27 (09) :2051-2061

[10] Synthesis, structure and cytotoxic activity of acetylenic derivatives of betulonic and betulinic acids [J].

Bebenek, Ewa ;

Chrobak, Elwira ;

Wietrzyk, Joanna ;

Kadela, Monika ;

Chrobak, Artur ;

Kusz, Joachim ;

Ksiazek, Maria ;

Jastrzebska, Maria ;

Boryczka, Stanislaw .

JOURNAL OF MOLECULAR STRUCTURE, 2016, 1106 :210-219

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