Synthesis, Antimicrobial Activity and Cytotoxicity of Novel (Piperidin-4-yl)adamantane-1-carboxylate N-Substituted...

The cyclic adamantane framework possesses unique properties such as bulkiness, symmetry, and high lipophilicity. Research aimed at discovering new pharmaceutical agents within the adamantane series continues. In the present work, a targeted modification was carried out to combine two pharmacophore fragments-adamantane and piperidine-within a single molecule. Based on a series of N-substituted piperidin-4-ones, the corresponding secondary alcohols were obtained by reduction with sodium borohydride in isopropanol and subsequent acylation of these alcohols with adamantane carbonyl chloride yielded the corresponding adamantane-carboxylate esters. The structure of the synthesized compounds was studied by NMR methods, including COSY (¹H-¹H), HMQC (¹H-¹³C) and HMBC (¹H-¹³C) techniques. The values of chemical shifts, multiplicities, and integrated intensities of ¹H and ¹³C signals in one-dimensional NMR spectra were determined. The results of COSY (¹H-¹H), HMQC (¹H-¹³C), and HMBC (¹H-¹³C) revealed homo- and heteronuclear interactions, confirming the structure of the studied compounds. The cytotoxic activities of the synthesized compounds were studied. It was found that the synthesized substituted piperidines bearing an adamantane fragment exhibit in vitro antimicrobial and antifungal activity against museum microbial strains (Escherichia coli ATCC 8739, Staphylococcus aureus ATCC 6538-P, Candida albicans ATCC 10231, Cryptococcus neoformans) and demonstrate significant advantages over the reference drugs used in clinical practice, such as fluconazole and ampicillin. These compounds are therefore recommended for further in-depth studies.