V. Palchykov^1*, A. Gaponov¹, N. Manko^2,3, N. Finiuk²,
О. Novikevych⁴, O. Gromyko³, R. Stoika2, N. Pokhodylo^3,4*

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.