TY - JOUR T1 - Synthesis and anti-tubercular activity of N(2)-arylbenzo[g]isoquinoline-5,10-dione-3-iminium bromides. JF - Org Biomol Chem Y1 - 2016 A1 - Rotthier, G A1 - Davie Cappoen A1 - Nguyen, Quang Trung A1 - Dang Thi, Tuyet Anh A1 - Vanessa Mathys A1 - Nguyen, Van Tuyen A1 - Huygen, K A1 - Maes, L A1 - Cos, P A1 - Abbaspour Tehrani, K KW - Antitubercular Agents KW - Dose-Response Relationship, Drug KW - Hydrocarbons, Brominated KW - Isoquinolines KW - Macrophages KW - Microbial Sensitivity Tests KW - Molecular Conformation KW - Mycobacterium tuberculosis KW - Structure-Activity Relationship KW - Tuberculosis, Multidrug-Resistant AB -

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.

VL - 14 CP - 6 U1 - http://www.ncbi.nlm.nih.gov/pubmed/26763748?dopt=Abstract M3 - 10.1039/c5ob02138c ER -