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

Tomas Gonec,Eva Kreckova,Pavel Bobal,Josef Jampilek,Jiri Kos,Josef Sujan,Libor Vesely,Peter Kollar,Lukas Placek,Aidan Coffey,Jiahui Guo,Katarina Kralova,Ales Imramovsky,Lenka Pavlacka,Matus Pesko

doi:10.3390/molecules17010613

Abstract

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.

Highlights

The presence of an amide or thioamide (-NHCO- or -NHCS-) group is characteristic of a number of biologically active compounds, e.g., [1,2,3,4,5,6,7,8,9]
Condensation of the chlorides of 2-quinaldic and 2-naphthoic acids with commercially available substituted amines yielded a series of thirty-five substituted quinoline-2-carboxamides 1–19c and thirty-three substituted naphthalene-2-carboxamides 20–38c
The prepared compounds were tested for their ability to inhibit photosynthetic electron transport (PET) in spinach chloroplasts (Spinacia oleracea L.) and for their antituberculosis/antimycobacterial activity

Summary

Introduction

The presence of an amide or thioamide (-NHCO- or -NHCS-) group is characteristic of a number of biologically active compounds, e.g., [1,2,3,4,5,6,7,8,9]. 50% of commercially available herbicides act by reversibly binding to photosystem II (PS II), a membrane-protein complex in the thylakoid membranes, which catalyses the oxidation of water and the reduction of plastoquinone [28], and thereby inhibit photosynthesis [29,30,31]. Both pharmaceuticals and pesticides are designed to target particular biological functions, and in some cases these functions overlap in their molecular target sites, or they target similar processes or molecules. Such chemical compounds are characterized by low toxicity on mammals as a result of quick metabolism and/or elimination of herbicide from the mammal system

Methods

Results

Conclusion