Tag Archives: DNA intercalation

Synthesis of the novel cage amides and imides and evaluation of their antibacterial and antifungal activity

V. Palchykov1*, A. Gaponov1, N. Manko2,3, N. Finiuk2,
О. Novikevych4, O. Gromyko3, R. Stoika2, N. Pokhodylo3,4*

1Research Institute of Chemistry and Geology, Oles Honchar Dnipro National University, Ukraine;
2Institute of Cell Biology of National Academy of Sciences of Ukraine, Lviv;
3Ivan Franko National University of Lviv, Ukraine;
4Stepan Gzhytskyi National University of Veterinary Medicine and Biotechnologies Lviv, Ukraine;
*e-mail: pokhodylo@gmail.com; palchikoff82@gmail.com

Received: 28 December 2021; Revised: 29 June 2022;
Accepted: 29 September 2022; Available on-line: 06 October 2022

Cage amides and imides bearing bicyclo[2.2.1]- and bicyclo[2.2.2]-subunits were synthesized and evaluated both for antimicrobial activity toward five key ESKAPE pathogenic bacteria: one Gram‐positive bacteria methicillin‐resistant Staphylococcus aureus (ATCC 43300), four Gram‐negative bacteria Escherichia coli (ATCC 25922), Klebsiella pneumoniae (ATCC 700603), Acinetobacter baumannii (ATCC 19606) and Pseudomonas aeruginosa (ATCC 27853) and for antifungal activity towards pathogenic fungal strains Candida albicans (ATCC 90028) and Cryptococcus neoformans var. Grubii (H99; ATCC 208821). Compound VP-4539 with bicyclo[2.2.2]octene motif demonstrated the highest cytotoxic activity towards C. neoformans, while human keratinocytes of HaCaT line, murine fibroblasts of Balb/c 3T3 line and mitogen-activated lymphocytes of peripheral human blood were found to be tolerant to its action. VP-4539 compound did not intercalate into salmon sperm DNA indicating that its cytotoxicity is not related to intercalation into nucleic acid.

Effect of a novel thiazole derivative and its complex with a polymeric carrier on stability of DNA in human breast cancer cells

N. S. Finiuk1,2, O. Yu. Klyuchivska1, I. I. Ivasechko1,
N. E. Mitina3, Yu. V. Ostapiuk2, M. D. Obushak2,
O. S. Zaichenko3, A. M. Babsky2, R. S. Stoika1,2*

1Institute of Cell Biology, NAS of Ukraine, Lviv, Ukraine;
2Ivan Franko National University of Lviv, Lviv, Ukraine;
3Lviv Polytechnic National University, Lviv, Ukraine;
*e-mail: stoika.rostyslav@gmail.com

Received: 26 January 2021; Accepted: 2021

Thiazole derivatives are perspective antitumor compounds characterized by a broad range of bioactivity, while polymeric carriers are widely used to enhance the efficiency of biological action of drugs, improve their biocompatibility and water solubility. Previously, we identified that the thiazole-based derivative BF1 (N-(5-benzyl-1,3-thiazol-2-yl)-3,5-dimethyl-1-benzofuran-2-carboxamide) possessed differential toxicity towards targeted tumor cell lines. The aim of the present work was to investigate the action in vitro of BF1 and its complex with the polymeric carrier (PC) poly(PEGMA-co-DMM) (BF1-РС complex) towards human breast adenocarcinoma cells of the MDA-MB-231 and MCF-7 lines. DNA comet analysis, diphenylamine DNA fragmentation assay, gel retardation assay of plasmid DNA, DNA intercalation assay using methyl green dye and fluorescent microscopy were used to study the effects of BF1 on DNA stability in breast cancer cells. The ІС50 of cytotoxic action towards MDA-MB-231 cells was 26.5 ± 2.9 µМ for BF1, while the ІС50 for the BF1-PC complex was 6.9 ± 0.4 µМ, and the PC demonstrated low toxicity (ІС50 ˃ 50 µМ). The BF1-PC complex possessed higher toxicity towards MCF-7 cells than free BF1, with ІС50 of 9.6 ± 0.8 µМ and 15.8 ± 0.9 µМ, respectively. BF1 and BF1-PC induced an increase in the number of damaged cells of the MDA-MB-231 line with blebbing of plasma membrane, condensed chromatin and/or fragmented nucleus and micronuclei formation. Both BF1 and the BF1-PC complex induced single-strand breaks in DNA and its fragmentation in treated MDA-MB-231 cells. The studied compounds were not bound to plasmid DNA and did not intercalate into DNA molecules.