Acid–Base Equilibrium and Self-Association in Relation to High Antitumor Activity of Selected Unsymmetrical Bisacridines Established by Extensive Chemometric Analysis

Michał Kosno; Tomasz Laskowski; Joanna Frąckowiak; Agnieszka Potęga; Agnieszka Kurdyn; Witold Andrałojć; Julia Borzyszkowska-Bukowska; Katarzyna Szwarc-Karabyka; Zofia Mazerska

doi:10.3390/molecules27133995

Acid–Base Equilibrium and Self-Association in Relation to High Antitumor Activity of Selected Unsymmetrical Bisacridines Established by Extensive Chemometric Analysis

Abstract

Unsymmetrical bisacridines (UAs) represent a novel class of anticancer agents previously synthesized by our group. Our recent studies have demonstrated their high antitumor potential against multiple cancer cell lines and human tumor xenografts in nude mice. At the cellular level, these compounds affected 3D cancer spheroid growth and their cellular uptake was selectively modulated by quantum dots. UAs were shown to undergo metabolic transformations in vitro and in tumor cells. However, the physicochemical properties of UAs, which could possibly affect their interactions with molecular targets, remain unknown. Therefore, we selected four highly active UAs for the assessment of physicochemical parameters under various pH conditions. We determined the compounds’ pKa dissociation constants as well as their potential to self-associate. Both parameters were determined by detailed and complex chemometric analysis of UV-Vis spectra supported bynuclear magnetic resonance (NMR) spectroscopy. The obtained results indicate that general molecular properties of UAs in aqueous media, including their protonation state, self-association ratio, and solubility, are strongly pH-dependent, particularly in the physiological pH range of 6 to 8. In conclusion, we describe the detailed physicochemical characteristics of UAs, which might contribute to their selectivity towards tumour cells as opposed to their effect on normal cells.

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Authors (9)

Michał Kosno
Tomasz Laskowski dr hab. inż.
Joanna Frąckowiak dr
Agnieszka Potęga dr hab. inż.
Agnieszka Kurdyn mgr inż.
Witold Andrałojć dr
- Polska Akademia Nauk, Instytut Chemii Bioorganicznej
Julia Borzyszkowska-Bukowska dr inż.
Katarzyna Szwarc-Karabyka dr inż.
Zofia Mazerska prof. dr hab. inż.

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Articles

Type:

artykuły w czasopismach

Published in:

MOLECULES no. 27,
ISSN: 1420-3049

Language:

English

Publication year:

2022

Bibliographic description:

Kosno M., Laskowski T., Frąckowiak J., Potęga A., Kurdyn A., Andrałojć W., Borzyszkowska-Bukowska J., Szwarc-Karabyka K., Mazerska Z.: Acid–Base Equilibrium and Self-Association in Relation to High Antitumor Activity of Selected Unsymmetrical Bisacridines Established by Extensive Chemometric Analysis// MOLECULES -Vol. 27,iss. 13 (2022), s.3995-

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