БНЗТ-2019

New Boron-Containing Lipids for NCT

Not scheduled

15m

Academpark

Speaker

Mrs Anna Druzina (A.N.Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences (INEOS RAS))

Description

Boron neutron capture therapy (BNCT) is a binary method for the treatment of cancer. Last years various tumor-targeting boron nanocarriers, including liposomes, have been intensively studied as potential candidates for a boron delivery system [1]. Liposomes composed of natural lipids are biodegradable and biologically inert and possess limited intrinsic toxicity. They tend to accumulate in tumor tissue much more than they do in normal tissues due to higher endocytic activity of some tumor cells combined with augmented local permeability of capillaries. Therefore, liposomal boron delivery systems are also considered to be useful candidates for BNCT due to the possibility of carrying a large amount of a boron [2-4]. Now we would like to present synthesis of novel cholesterol-type boron-containing lipids based on the closo-dodecaborate anion and cobalt and iron bis(dicarbollides). Desired conjugates were prepared using nucleophilic ring-opening reactions of cyclic oxonium derivatives of cobalt bis(dicarbollide) and closo-dodecaborate with hydroxy derivative of cholesterol, namely 3β-(2-hydroxyethoxy)cholest-5-ene. Another series of boronated cholesterols were prepared by the Cu(I)-catalyzed 1,3-dipolar cycloaddition of boron-containing alkyne and cholesterol azido-derivative, 3β-(2-azidoethoxy)cholest-5-ene, to form a triazole. Boron-clusters bearing terminal acetylenes were prepared by the nucleophilic ring-opening reactions of 1,4-dioxane or tetrahydropyran derivatives of cobalt bis(dicarbollide) with the corresponding alcoholates and phenolates [5-7].

Summary

Convenient ways to synthesize libraries of boron cluster-modified cholesterol for liposomal boron delivery systems in the boron neutron capture therapy (BNCT) of tumors are developed.
References
1. S. Ban, H. Nakamura, in Handbook of Boron Science with Applications in Organometallics, Catalysis, Materials and Medicine, Vol. 4, Boron in Medicine (Eds.: N. S. Hosmane, R. Eagling), World Scientific, London, 2018, 49.
2. B. Pietras, A. B. Olejniczak, S. Tachikawa, H. Nakamura, Z. J. Les´nikowski, Bioorg. Med. Chem., 2013, 21, 1136.
3. Nakamura, in Boron Science: New Technologies and Applications (Ed.: N. S. Hosmane), CRC Press, Boca Raton, 2012, 165.
4. Nakamura, Future Med. Chem., 2013, 5, 715.
5. A. Wojtczak, A. Andrysiak, B. Grüner, Z.J. Lesnikowski, Chem. Eur. J., 2008, 14, 10675.
6. D. Kosenko, I.A. Lobanova, L.A. Chekulaeva, I.A. Godovikov, V.I. Bregadze, Russ. Chem. Bull., 2013, 62, 497.
7. V. Shmal’ko, I.B. Sivaev, V.I. Bregadze, L.V. Kovalenko, Inorg. Lett., 2015, 2, 1.
Acknowledgements
The work was supported by Russian Foundation for Basic Research (grant 17-53-80099_ BRICS), by the Department of Science and Technology, Government of India (DST/IMRCD/BRICS/PilotCall1/BGNCDT/2017(G)), and the National Natural Science Foundation of China (51761145021, BRICS Research Project).