Spermine amides of selected triterpenoid acids: Dynamic supramolecular systems formation influences cytotoxicity of the drugs

Uladzimir Bildziukevich, Matej Malik, Zulal Özdemir, Lucie Rarova, Miroslav Slouf, David Saman, Jan Sarek, Nonappa Nonappa, Zdenek Wimmer

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Cancer has been a global disease of great importance, and a need for novel cytotoxic drugs has still been eminent. A series of spermine amides of several selected triterpene acids (betulonic, heterobetulonic, oleanolic, ursolic and platanic acid) has been synthesized to search for new cytotoxic and antimicrobial agents. The compounds have also been subjected to the investigation of their physico-chemical characteristics (ability to self-assemble), and to an in silico comparative calculation of their physico-chemical and ADME parameters. In the in vitro screening tests with several target compounds (8a–8c and 11c), their cytotoxicity changed with the prolonged time, which effect appeared to be a result of a formation of dynamic supramolecular networks. This phenomenon is important in investigation of the effect of self-assembly on biological activity. The most important compounds in this series were spermine derivatives of heterobetulonic acid (3b) and ursolic acid (8b), showing cytotoxicity < 5 µM and < 10 µM, respectively, on all tested cancer cell lines. Comparable cytotoxicity was also displayed by 13b, formerly a model compound prepared for testing of the synthetic procedures, the 1,2-diaminoethane derivative. The target compounds 3b and 8b displayed antimicrobial activity on Staphylococcus aureus, Streptococcus mutans and Listeria monocytogenes at a concentration 6.25 µM. Supramolecular characteristics of several compounds were documented by the TEM and SEM micrographs showing fibrous, partially helical, networks, and UV measurements showing changes in the intensity of UV signals, also indicating a formation of supramolecular systems.
Original languageEnglish
Pages (from-to)484-491
Number of pages8
JournalJOURNAL OF MATERIALS CHEMISTRY. B
Volume8
Issue number3
DOIs
Publication statusPublished - 2020
MoE publication typeA1 Journal article-refereed

Fingerprint Dive into the research topics of 'Spermine amides of selected triterpenoid acids: Dynamic supramolecular systems formation influences cytotoxicity of the drugs'. Together they form a unique fingerprint.

  • Projects

    HYBER: The Academy of Finland's Centre of Excellence in Molecular Engineering of Biosynthetic Hybrid Materials research (2014-2019)

    Cherian, T., Nonappa, N., Ikkala, O., Bertula, K., Poutanen, M., Morits, M., Hynninen, V., Myllymäki, T., Toivonen, M., Sohrabi, F., Haataja, J., Sanchez Sanchez, A. & Rissanen, S.

    01/01/201730/06/2020

    Project: Academy of Finland: Other research funding

    Equipment

    OtaNano

    Anna Rissanen (Manager)

    Aalto University

    Facility/equipment: Facility

  • Cite this