Adamantane acid esters with alkoxyaryl alcohols: Synthesis, antiproliferative activity, and influence on microtubule network of tumor cells
- Authors: Zefirov N.A.1, Nurieva E.V.1, Pikulina Y.A.2, Ogon´kov A.V.3, Wobith B.3, Kuznetsov S.A.3, Zefirova O.N.1,4
-
Affiliations:
- M. V. Lomonosov Moscow State University, Department of Chemistry
- M. V. Lomonosov Moscow State University, Department of Fundamental Medicine
- Institute of Biological Sciences, University of Rostock
- Institute of Physiologically Active Compounds, Russian Academy of Sciences
- Issue: Vol 66, No 8 (2017)
- Pages: 1503-1509
- Section: Full Articles
- URL: https://journals.rcsi.science/1066-5285/article/view/241142
- DOI: https://doi.org/10.1007/s11172-017-1915-4
- ID: 241142
Cite item
Abstract
Adamantaneacetic and adamantanecarboxylic acid esters containing 3-hydroxy-4-methoxybenzyl, 3,4,5-trimethoxybenzyl, or 5-(hydroxymethyl)-2-methoxyphenyl groups were synthesized as unusual analogs of natural antitumor and anti-tubulin agents combretastatin A-4 and 2-methoxyestradiol. The compounds were found to possess noticeable cytotoxicity to epithelial human carcinoma cell line A549 (EC50 = 4.3—81 μmol L–1). An ability to cause complete depolymerization of microtubule network of A549 cells was demonstrated for 5-(hydroxymethyl)-2-methoxyphenyl adamantan-1-ylacetate (6a) at a concentration of 100 μmol L–1. Ester 6a belongs to a new structural type, which is unusual for the ligands of the tubulin colchicine domain, and is an interesting lead compound for further structural optimization.
About the authors
N. A. Zefirov
M. V. Lomonosov Moscow State University, Department of Chemistry
Email: olgaz@org.chem.msu.ru
Russian Federation, Build. 3, 1 Leninskie Gory, Moscow, 119991
E. V. Nurieva
M. V. Lomonosov Moscow State University, Department of Chemistry
Email: olgaz@org.chem.msu.ru
Russian Federation, Build. 3, 1 Leninskie Gory, Moscow, 119991
Yu. A. Pikulina
M. V. Lomonosov Moscow State University, Department of Fundamental Medicine
Email: olgaz@org.chem.msu.ru
Russian Federation, Korp. 1, 27 Lomonosovsky prosp., Moscow, 119991
A. V. Ogon´kov
Institute of Biological Sciences, University of Rostock
Email: olgaz@org.chem.msu.ru
Germany, Rostock, 18106
B. Wobith
Institute of Biological Sciences, University of Rostock
Email: olgaz@org.chem.msu.ru
Germany, Rostock, 18106
S. A. Kuznetsov
Institute of Biological Sciences, University of Rostock
Email: olgaz@org.chem.msu.ru
Germany, Rostock, 18106
O. N. Zefirova
M. V. Lomonosov Moscow State University, Department of Chemistry; Institute of Physiologically Active Compounds, Russian Academy of Sciences
Author for correspondence.
Email: olgaz@org.chem.msu.ru
Russian Federation, Build. 3, 1 Leninskie Gory, Moscow, 119991; 1 Severnyi pr-d, Chernogolovka, Moscow Region, 142432