The link between relative stability constant of DNA- and BSA-chromenopyrimidine complexes and cytotoxicity towards human breast cancer cells (MCF-7)

Sizwe J Zamisa; Adesola A Adeleke; Nikita Devnarain; Mahasin Abdel Rhman; Peter M O Owira; Bernard Omondi

doi:10.1039/d3ra01741a

The link between relative stability constant of DNA- and BSA-chromenopyrimidine complexes and cytotoxicity towards human breast cancer cells (MCF-7)

RSC Adv. 2023 Jul 19;13(32):21820-21837. doi: 10.1039/d3ra01741a.

Authors

Sizwe J Zamisa¹, Adesola A Adeleke¹, Nikita Devnarain², Mahasin Abdel Rhman², Peter M O Owira², Bernard Omondi¹

Affiliations

¹ School of Chemistry and Physics, University of KwaZulu-Natal Private Bag X54001 Durban 4000 South Africa owaga@ukzn.ac.za.
² Molecular and Clinical Pharmacology Research Laboratory, Department of Pharmacology, Discipline of Pharmaceutical Science, University of KwaZulu-Natal Private Bag X54001 Durban 4000 South Africa.

Abstract

In this study, we synthesized and characterized ten chromenopyrimidine derivatives using analytical and spectroscopic methods. Studies on DNA and albumin binding affinity, as well as cytotoxicity tests on human breast cancer (MCF-7) cells, of the chromenopyrimidines, were conducted. The natural logarithm of the relative stability constant of DNA- and BSA-chromenopyrimidine complexes [ln(K_DNA/K_BSA)] was used as a criterion for selecting compounds for cytotoxicity studies. We found that ln(K_DNA/K_BSA) was inversely related to IC₅₀ values of the compounds in MCF-7 cells. The antiproliferative effects of the compounds were found to induce apoptosis in MCF-7 cells, which is a desired mechanism of cell death. Correlations between the DNA and albumin binding affinities of chromenopyrimidines were established. We propose that this relationship approach can, for a given set of compounds, assist in predicting the cytotoxicity of potential drug candidates towards MCF-7 cells based on their experimentally determined CT-DNA and BSA binding affinities.