Synthesis and anti-tubercular activity of N(2)-arylbenzo[g]isoquinoline-5,10-dione-3-iminium bromides

Organic & Biomolecular Chemistry
G RotthierK Abbaspour Tehrani

Abstract

Tuberculosis has remained a challenge for medicinal chemists worldwide. In the framework of a collaborative program to identify and evaluate novel antitubercular candidate compounds, the biological properties of benzo[g]isoquinoline-5,10-diones have been found to be very promising. In this paper we have further expanded the library by incorporation of an amidinium moiety into the benzo[g]isoquinoline-5,10-dione scaffold. The presence of this functional group also increased the solubility of the quinones in polar solvents. To this purpose N(2)-arylbenzo[g]isoquinoline-5,10-dione-3-iminium bromides were synthesized in a straightforward way by means of a reaction of anilines with 2-(bromomethyl)-3-(cyanomethyl)-1,4-dimethoxynaphthalene. Following the biological evaluation, N(2)-(4-chlorophenyl)-5,10-dioxobenzo[g]isoquinoline-3(2H)-iminium bromide (MIC = 1.16 μM, CC50 = 28.51 μM, SI = 24.58) was selected as the most promising representative. Apart from the nano-molar anti-mycobacterial activity, the compound was able to target intracellular residing Mycobacterium tuberculosis and the susceptibility of a multi-drug-resistant strain towards the compound was confirmed.

References

Jan 1, 1993·Progress in Medicinal Chemistry·J V Greenhill, P Lue
Feb 13, 1999·Journal of Clinical Microbiology·B A HannaA M Vannier
Aug 24, 1999·Infection and Immunity·V A SnewinD B Young
Sep 4, 2003·The Journal of Experimental Medicine·Dirk SchnappingerGary K Schoolnik
Jul 1, 2004·Bioorganic & Medicinal Chemistry Letters·Toshiki MurataTimothy B Lowinger
Nov 16, 2007·Organic & Biomolecular Chemistry·Tobias BrücklThomas Carell
Jul 5, 2008·Nature Protocols·Guillermo RepettoJorge L Zurita
Sep 9, 2008·The Journal of Organic Chemistry·Sven ClaessensNorbert De Kimpe
Jan 10, 2012·Chemical Society Reviews·Tom R M Rauws, Bert U W Maes
Feb 4, 2012·European Journal of Medicinal Chemistry·D ForgeJ J Vanden Eynde
Apr 10, 2013·European Journal of Medicinal Chemistry·Davie CappoenKris Huygen
Jul 16, 2013·European Journal of Medicinal Chemistry·Pieter ClaesNorbert De Kimpe
Mar 13, 2014·Journal of Medicinal Chemistry·Davie CappoenNorbert De Kimpe
Sep 10, 2014·Organic & Biomolecular Chemistry·Dipakranjan MalKumar Biradha

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Citations

Feb 26, 2019·Organic & Biomolecular Chemistry·Robert J SmetsKourosch Abbaspour Tehrani

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