Antibacterial, antibiofilm and anti-quorum sensing activities of 1,2,3,5-tetrazine derivatives linked to a benzothiazole moiety

Abstract A series of known tetrazine derivatives, containing benzothiazole scaffold, were prepared during the coupling reactions of selected diazotized 2-aminobenzo[d]thiazole derivatives with p-acetaminophen. The as-prepared compounds were characterized based on NMR and MS spectrometry. The antibacterial and anti-biofilm activities of the synthesized compounds were evaluated by microdilution method, whereas the anti-quorum sensing effect was carried out using assay for the inhibition of violacein formation. As a result, compounds 4a, 4b and 4c revealed minimum inhibitory concentrations and minimum bactericidal concentrations ranging from 8 to 128 µg/mL and from 32 to 256 µg/mL, respectively. Compounds 4a (52-86.5%), 4b (57.7-79.4%) and 4c (59.9-80.3%) prevented biofilm formation in all the four bacteria tested with percentages of inhibition more than 50%. The concentrations of 4a, 4b and 4c that inhibited 50% of violacein production were found to be 62.71, 28.56 and 107.45 µg/mL, respectively, thus attesting that these compounds possess anti-quorum sensing activity. Noteworthy, our previous investigation attested that these compounds are non-cytotoxic on the human mammalian cells Vero. This novel contribution demonstrates the antibacterial, antibiofilm and anti-quorum sensing activities of tetrazine-based benzothiazoles, which might be prospected as scaffolds for the discovery of efficient antibiotics with decreased risk of microbial drug resistance. Competing Interest Statement The authors have declared no competing interest. Footnotes Email: lyndy.mcgaw{at}up.ac.za Email: tsemeugne{at}yahoo.fr, rostandrostand301{at}gmail.com; borisarnaud105{at}gmail.com, mpierrendi{at}yahoo.fr Email: fabrice.boyom{at}fulbrightmail.org (F.F.B.).