Synthesis and Evaluation of Antibacterial Activity of 1,2,4-Oxadiazole-Containing Biphenylcarboxylic Acids
- PDF / 710,514 Bytes
- 9 Pages / 612 x 792 pts (letter) Page_size
- 9 Downloads / 187 Views
hesis and Evaluation of Antibacterial Activity of 1,2,4-Oxadiazole-Containing Biphenylcarboxylic Acids M. V. Tarasenkoa,*, S. I. Presnukhinaa, S. V. Baikovb, and A. A. Shetneva a
M.V. Dorogov Center for Transfer of Pharmaceutical Technologies, K.D. Ushinsky Yaroslavl State Pedagogical University, Yaroslavl, 150000 Russia b St. Petersburg State University, St. Petersburg, 199034 Russia *e-mail: [email protected] Received April 21, 2020; revised April 21, 2020; accepted April 30, 2020
Abstract—A one-pot method for the synthesis of biphenylcarboxylic acids containing 1,2,4-oxadiazole ring in the NaOH–DMSO system was developed. The results of in vitro experiments showed that the synthesized compounds exhibit antibacterial activity against susceptible strains of E. coli and S. aureus. Keywords: heterocycles, dicarboxylic acid anhydrides, basic catalysis, antimicrobial activity, amidoximes
DOI: 10.1134/S1070363220090042 1,2,4-Oxadiazole derivatives have recently attracted much attention of researchers due to the wide use of these heterocycles both in medicinal chemistry and in materials science [1–5]. For example, 1,2,4-oxadizolecontaining drugs such as Ataluren (Duchenne’s disease) [6], Azilsartan (treatment of hypertension) [7], Opikapon (Parkinson’s disease) [8], Oxolamine (a cough suppressant) [9], Amenamivir (HIV therapy) [10], and Naldemidine (pain reliever) [11] are successfully used in medical practice. One of the priority areas of medical application of 1,2,4-oxadiazoles is the search for new antibacterial agents, primarily against resistant bacterial strains [12– 20]. This is due to the fact that the growth of resistance of pathogenic microorganisms to antibacterial drugs is a global threat of the XXI century [21–26]. Earlier, we have developed an efficient method for the synthesis of 1,2,4-oxadiazoles with different functional peripheries based on the condensation of amidoximes with carboxylic acids [27] or their derivatives [28–31]. Subsequently, this approach was successfully applied to obtain biologically active derivatives of 1,2,4-oxadiazole [32–36] (including those with antimicrobial activity [37]) and synthetic building blocks valuable for drug design [38, 39]. Previously, we have reported the reaction of amidoximes with dicarboxylic acid anhydrides, which makes it possible to obtain 1,2,4-oxadiazole systems
containing a carboxyl group in a step-economic way under mild conditions [40]. In particular, the 1,2,4-oxadiazole derivative with 2,2′-biphenylcarboxylic acid was obtained for the first time (Scheme 1). Since 2,2′-biphenyldicarboxylic acids and their derivatives are of interest as potential antimicrobial agents [41–43], we studied the reactions of various aromatic and heterocyclic amidoximes with diphenic anhydrides, and also evaluated antibacterial activity of the resulting hybrid structures against Staphylococcus aureus and Escherichia coli strains, which are examples of important pathogenic microorganisms. Amidoximes 2a–2h were obtained by reacting commercially available nitriles 1a–1h with a
Data Loading...
