ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Antimicrobial activity and DNA/HSA interaction of fluorinated 3,6,9-trisubstituted acridines

Patrik Nunhart, Eva Konkoľová, Ladislav Janovec, Jana Kašpárková, Jaroslav Malina, Viktor Brabec, Mária Matejová, Beata Miltáková, Ladislav Novotny, Oludotun A. Phillips, Edet Udo, and Mária Kozurkova

Department of Biochemistry, Institute of Chemistry, Faculty of Science, P. J. Šafárik University in Košice, Košice, Slovak Republic

E-mail: maria.kozurkova@upjs.sk

Received: 23 October 2019  Accepted: 27 January 2020

Abstract:

A series of four new 3,6,9-trisubstituted acridine derivatives (two with fluorine substituents on phenyl ring) were synthesized and their interaction with calf thymus DNA and HSA was investigated using a combination of biochemical, biophysical and biological techniques. Analysis using fluorescent spectra provided valuable information about the formation of the acridine–DNA complex, while several other experiments suggest that acridine may bind to DNA through intercalation. These observations are further supported by LD spectral analysis, viscosity measurements and DNA melting studies. The interaction between HSA and four compounds were studied by fluorescence quenching spectra. In addition, the method was used for the calculation of characteristic binding parameters. These result and result obtained by synchronous fluorescence spectra of acridines with HSA determined that compounds create complexes with HSA and induce conformational changes. K_B values were found to be of 1.51–7.34 × 10⁶ M⁻¹. The studied 8c compound were the most sensitive against S. epidermidis ATCC 12228.

Keywords: 3,6,9-Trisubstituted acridine derivatives; Fluorine; Calf thymus DNA; Human serum albumin; Spectroscopic techniques; Antimicrobial activity

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-020-01079-4

Chemical Papers 74 (7) 2327–2337 (2020)