Monoterpene indole alkaloids as leads for targeting multidrug resistant cancer cells from the African medicinal plant Tabernaemontana elegans

被引:13
作者
Ferreira, Maria-Jose U. [1 ]
Paterna, Angela [1 ]
机构
[1] Univ Lisbon, Res Inst Med & Pharmaceut Sci iMedUL, Fac Pharm, Ave Prof Gama Pinto, P-1649003 Lisbon, Portugal
关键词
ABC-transporters; Apocynaceae; Apoptosis; Collateral sensitivity; BCRP; MRP1; and P-gp; APOPTOSIS-INDUCING ACTIVITY; COLLATERAL SENSITIVITY; NATURAL-PRODUCTS; P-GLYCOPROTEIN; MACROCYCLIC DITERPENES; COLON ADENOCARCINOMA; EFFLUX MODULATION; DRUG DISCOVERY; HCT116; COLON; DERIVATIVES;
D O I
10.1007/s11101-019-09615-1
中图分类号
Q94 [植物学];
学科分类号
071001 ;
摘要
Multidrug resistance (MDR) is the main challenge in cancer treatment. Several mechanisms of MDR have been proposed, such as an increased drug efflux due to the overexpression of ABC drug transporter proteins, or a deregulation of apoptosis. Thus, the development of ABC-transporter modulators and the search for effective apoptosis inducers have been considered realistic strategies for overcoming MDR. Exploiting collateral sensitivity is also comprised among the most promising approaches to tackle MDR. Aiming at obtaining a library of monoterpene indole alkaloids for overcoming MDR, we have been carrying out the phytochemical study of the African medicinal plant Tabernaemontana elegans (Apocynaceae), by using both approaches isolation and molecular derivatization. The results, summarized in this review, showed that several indole alkaloids, of both natural origin or obtained by derivatization, are promising potential lead structures for reversing MDR.
引用
收藏
页码:971 / 987
页数:17
相关论文
共 62 条
[1]   Structure of P-Glycoprotein Reveals a Molecular Basis for Poly-Specific Drug Binding [J].
Aller, Stephen G. ;
Yu, Jodie ;
Ward, Andrew ;
Weng, Yue ;
Chittaboina, Srinivas ;
Zhuo, Rupeng ;
Harrell, Patina M. ;
Trinh, Yenphuong T. ;
Zhang, Qinghai ;
Urbatsch, Ina L. ;
Chang, Geoffrey .
SCIENCE, 2009, 323 (5922) :1718-1722
[2]  
[Anonymous], MOL CANC THER
[3]  
[Anonymous], PROGR CHEM ORGANIC N
[4]  
[Anonymous], PLANT RESOURCE TROPI
[5]  
[Anonymous], 2009, MED NATURAL PRODUCTS
[6]   Cytotoxic Indole Alkaloids from Tabernaemontana divaricata [J].
Bao, Mei-Fen ;
Yan, Ju-Ming ;
Cheng, Gui-Guang ;
Li, Xing-Yao ;
Liu, Ya-Ping ;
Li, Yan ;
Cai, Xiang-Hai ;
Luo, Xiao-Dong .
JOURNAL OF NATURAL PRODUCTS, 2013, 76 (08) :1406-1412
[7]   Optimizing the macrocyclic diterpenic core toward the reversal of multidrug resistance in cancer [J].
Baptista, Rafael ;
Ferreira, Ricardo J. ;
dos Santos, Daniel J. V. A. ;
Fernandes, Miguel X. ;
Ferreira, Maria-Jose U. .
FUTURE MEDICINAL CHEMISTRY, 2016, 8 (06) :629-645
[8]   THE ALKALOIDS OF TABERNANTHE-IBOGA .4. THE STRUCTURES OF IBOGAMINE, IBOGAINE, TABERNANTHINE AND VOACANGINE [J].
BARTLETT, MF ;
DICKEL, DF ;
TAYLOR, WI .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1958, 80 (01) :126-136
[9]   STRUCTURES OF TABERNAELEGANTINES A-D AND TABERNAELEGANTININES A AND B, NEW INDOLE ALKALOIDS FROM TABERNAEMONTANA-ELEGANS [J].
BOMBARDELLI, E ;
BONATI, A ;
GABETTA, B ;
MARTINELLI, EM ;
MUSTICH, G ;
DANIELI, B .
JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1976, (13) :1432-1438
[10]   β-Carboline alkaloids:: Biochemical and pharmacological functions [J].
Cao, Rihui ;
Peng, Wenlie ;
Wang, Zihou ;
Xu, Anlong .
CURRENT MEDICINAL CHEMISTRY, 2007, 14 (04) :479-500