Monoterpene indole alkaloids as leads for targeting multidrug resistant cancer cells from the African medicinal plant Tabernaemontana elegans Maria-Jose ´ U. Ferreira . Angela Paterna Received: 17 January 2019 / Accepted: 6 June 2019 Ó Springer Nature B.V. 2019 Abstract 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 modula- tors and the search for effective apoptosis inducers have been considered realistic strategies for overcom- ing 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. Keywords ABC-transporters Á Apocynaceae Á Apoptosis Á Collateral sensitivity Á BCRP, MRP1, and P-gp Abbreviations ABC ATP Binding Cassette ABCB1 ATP Binding Cassette, Subfamily B, Member 1 ABCC1 ATP Binding Cassette, Subfamily C, Member 1 ABCG2 ATP Binding Cassette, Subfamily G, Member 2 ADMET Absorption, distribution, metabolism, excretion, toxicity ADP- ribose Adenosine diphosphate ribose ATP Adenosine triphosphate BBB Blood–brain barrier Bcl-2 B-cell lymphoma 2 BCRP Breast cancer resistance protein BHK- 21-wt Baby hamster kidney-21 wild-type cells CS Collateral sensitivity FAR Fluorescence activity ratio GSH Glutathione GSSG Glutathione disulphide HCT116 Human colon carcinoma cell line HEK293 Human embryonic kidney 293 cells HepG2 Human liver carcinoma cell line HuH-7 Human liver carcinoma cell line IC 50 Sample concentration causing 50% inhibition log P Octanol/water partition coefficient MDR Multidrug resistance M.-J. U. Ferreira (&) Á A. Paterna Faculty of Pharmacy, Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal e-mail: mjuferreira@ff.ul.pt 123 Phytochem Rev https://doi.org/10.1007/s11101-019-09615-1