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

  • Maria-José U. FerreiraEmail author
  • Angela Paterna


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.


ABC-transporters Apocynaceae Apoptosis Collateral sensitivity BCRP, MRP1, and P-gp 



ATP Binding Cassette


ATP Binding Cassette, Subfamily B, Member 1


ATP Binding Cassette, Subfamily C, Member 1


ATP Binding Cassette, Subfamily G, Member 2


Absorption, distribution, metabolism, excretion, toxicity


Adenosine diphosphate ribose


Adenosine triphosphate


Blood–brain barrier


B-cell lymphoma 2


Breast cancer resistance protein


Baby hamster kidney-21 wild-type cells


Collateral sensitivity


Fluorescence activity ratio




Glutathione disulphide


Human colon carcinoma cell line


Human embryonic kidney 293 cells


Human liver carcinoma cell line


Human liver carcinoma cell line


Sample concentration causing 50% inhibition

log P

Octanol/water partition coefficient


Multidrug resistance


Multidrug resistance associated protein 1


3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt


3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide


Mouse embryonic fibroblast cells


Parental cells




Reactive oxygen species


Relative resistance ratio


Structure-activity relationship


Human Caucasian colon adenocarcinoma


X-linked inhibitor of apoptosis protein



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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Faculty of Pharmacy, Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL)University of LisbonLisbonPortugal

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