Search for Antiviral Preparations in Series of New Derivatives of N-Substituted Piperidines
Gulmira S. Akhmetova,
Ulzhalgas B. Issayeva,
Kaldybay D. Praliyev,
Ilya S. Korotetskiy,
Tulegen M. Seilkhanov,
Samir A. Ross,
Manas T. Omyrzakov,
Ubaidilla M. Datkhayev,
Khaidar S. Tassibekov,
Lyudmila N. Ivanova,
Natalya V. Zubenko
Affiliations
Gulmira S. Akhmetova
Laboratory of Synthetic and Natural Medicinal Compounds Chemistry, A.B. Bekturov Institute of Chemical Sciences JSC, 106 Sh. Ualikhanov St., Almaty 050010, Kazakhstan
Ulzhalgas B. Issayeva
Laboratory of Synthetic and Natural Medicinal Compounds Chemistry, A.B. Bekturov Institute of Chemical Sciences JSC, 106 Sh. Ualikhanov St., Almaty 050010, Kazakhstan
Kaldybay D. Praliyev
Laboratory of Synthetic and Natural Medicinal Compounds Chemistry, A.B. Bekturov Institute of Chemical Sciences JSC, 106 Sh. Ualikhanov St., Almaty 050010, Kazakhstan
Ilya S. Korotetskiy
Scientific Center for Anti-Infectious Drugs JSC, Almaty 050060, Kazakhstan
Tulegen M. Seilkhanov
The Laboratory of Engineering Profile of NMR Spectroscopy, Sh. Ualikhanov Kokshetau State University, Kokshetau 020000, Kazakhstan
Samir A. Ross
National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, Oxford, MS 38677, USA
Manas T. Omyrzakov
School of Pharmacy, Asfendiyarov Kazakh National Medical University, Almaty 050000, Kazakhstan
Ubaidilla M. Datkhayev
School of Pharmacy, Asfendiyarov Kazakh National Medical University, Almaty 050000, Kazakhstan
Khaidar S. Tassibekov
Laboratory of Synthetic and Natural Medicinal Compounds Chemistry, A.B. Bekturov Institute of Chemical Sciences JSC, 106 Sh. Ualikhanov St., Almaty 050010, Kazakhstan
Lyudmila N. Ivanova
Scientific Center for Anti-Infectious Drugs JSC, Almaty 050060, Kazakhstan
Natalya V. Zubenko
Scientific Center for Anti-Infectious Drugs JSC, Almaty 050060, Kazakhstan
Cyanohydrin synthesis, as the simplest preparative method for introducing a carboxyl group into a piperidine molecule, has been used to obtain potentially biologically active piperidinecarboxylic acids, which have alkyl and arylalkyl radicals at the nitrogen atom of the piperidine ring. Hydrochlorides of cyclopropanecarboxylic acid esters based on piperidinecarboxylic acids, as well as hydrochlorides of fluorobenzoic acid esters of N-substituted piperidines, have been synthesized. The purpose of this study was to search for antiviral drugs among new piperidine derivatives. 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 antiviral and cytotoxic activities of the synthesized compounds were studied. The antiviral activity in vitro was determined according to the therapeutic regimen against the influenza A/Swine/Iowa/30 (H1N1) virus on the MDCK cell model. The cytotoxicity of the studied substances in vitro was assessed using the MTT test. Based on the results of the antiviral activity against the influenza A virus, it can be concluded that all substances are effective against the influenza A/H1N1 virus compared to the commercial preparations Tamiflu and Rimantadine.
