Organizing co mmittee

ADDUCTS OF NATURAL TRITERPENOID ACIDS WITH 
MITOCHONDRIA-TARGETED CATIONIC COMPOUND F16, 
PROMISING AS NEW ANTICANCER DRUGS 
Eldar Valerievich Davletshin, Darya Alexandrovna Nedopekina, Anna Yulievna 
Spivak 
Institute of Petrochemistry and Catalysis, Ufa Federal Research Center, Russian 
Academy of Sciences, Prospekt Oktyabrya 141, Ufa, Republic of Bashkortostan, 
450075, Russia 
In order to design an effective anti-cancer drugs, have been synthesized a series of 
conjugates of natural pentacyclic triterpene acids (betulinic, ursolic, oleanolic, maslinic, 
and corosolic acids) with a mitochondria-targeted delocalized lipophilic cationic 
compound F16 [E-4-(1H-indol-3-ylvinyl)-
N
-methylpyridinium iodide]. A fragment of 
the lipophilic membrane-penetrating compound F16 was used as a vector for the 
transfer of pentacyclic triterenoids through cell membranes, selective delivery into the 
mitochondria of cancer cells, and simultaneously as a fluorescent probe. The most 
hybrid molecules demonstrated multiple synergistic effect of antitumor activity (≈50-
100 times) 
in vitro
tests on human leukemia tumor cell lines (U937, K562 and Jurkat), 
breast adenocarcinoma (MCF-7) and human lung adenocarcinoma cells (A549 and 
H1299). The study of the mechanism of antitumor activity in relation to the MCF-7 cell 
line showed that the antitumor activity of the conjugates is due to their prooxidant effect 
associated with the massive generation of reactive oxygen species in cancer cells, as 
well as the antiproliferative effect causing cell cycle arrest at the G0/G1 phase. 
Visualization of the distribution of conjugates in intracellular organelles, performed 
using the method of confocal microscopy, indicated a high degree of their localization 
in the mitochondria of cancer cells. (The work was carried out in collaboration with the 
Mari State University, Yoshkar-Ola and the Institute of Theoretical and Experimental 
Biophysics of the Russian Academy of Sciences, Laboratory of Mitochondrial 
Transport, Pushchino). 
This work was performed under financial support from the 
Russian Science Foundation (Grant 23-23-00098). 

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