Investigating the Spectrum of Biological Activity of Substituted Quinoline-2-Carboxamides and Their Isosteres

Molecules

Tomas Gonec¹  Pavel Bobal¹  Josef Sujan¹  Matus Pesko¹  Jiahui Guo¹  Katarina Kralova¹  Lenka Pavlacka¹  Libor Vesely¹  Eva Kreckova¹  Jiri Kos¹  Aidan Coffey¹  Peter Kollar¹  Ales Imramovsky¹  Lukas Placek¹ 

[1] ¹Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1/3, 61242 Brno, Czech Republic

关键词: quinolines;    naphthalene;    lipophilicity;    photosynthetic electron transport inhibition;    spinach chloroplasts;    in vitro antimycobacterial activity;    in vitro cytotoxicity;   

DOI  :  10.3390/molecules17010613

来源: mdpi

【 摘 要 】

In this study, a series of thirty-five substituted quinoline-2-carboxamides and thirty-three substituted naphthalene-2-carboxamides were prepared and characterized. They were tested for their activity related to the inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. Primary in vitro screening of the synthesized compounds was also performed against four mycobacterial species. N-Cycloheptylquinoline-2-carboxamide, N-cyclohexylquinoline-2-carboxamide and N-(2-phenylethyl)quinoline-2-carboxamide showed higher activity against M. tuberculosis than the standards isoniazid or pyrazinamide and 2-(pyrrolidin-1-ylcarbonyl)quinoline and 1-(2-naphthoyl)pyrrolidine expressed higher activity against M. kansasii and M. avium paratuberculosis than the standards isoniazid or pyrazinamide. The most effective antimycobacterial compounds demonstrated insignificant toxicity against the human monocytic leukemia THP-1 cell line. The PET-inhibiting activity expressed by IC₅₀ value of the most active compound N-benzyl-2-naphthamide was 7.5 μmol/L. For all compounds, the structure-activity relationships are discussed.

【 授权许可】

CC BY   
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.