Dzoyem Jean Paul, Tsemeugne Joseph, Pone Kamdem Boniface, Foyou Meupiap Rostand, Kuate Boris Arnaud, Mkounga Pierre, Fekam Boyom Fabrice, McGaw Lyndy Joy
Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon.
Phytomedicine Programme, Department of Paraclinical Sciences, University of Pretoria, Pretoria, South Africa.
PLoS One. 2025 Jun 3;20(6):e0318135. doi: 10.1371/journal.pone.0318135. eCollection 2025.
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.
通过将选定的重氮化2-氨基苯并[d]噻唑衍生物与对乙酰氨基酚进行偶联反应，制备了一系列含苯并噻唑骨架的已知四嗪衍生物。通过核磁共振（NMR）和质谱（MS）对所制备的化合物进行了表征。采用微量稀释法评估了合成化合物的抗菌和抗生物膜活性，而采用检测紫色杆菌素形成抑制的方法来评估其群体感应抑制效果。结果，化合物4a、4b和4c的最低抑菌浓度和最低杀菌浓度分别为8至128μg/mL和32至256μg/mL。化合物4a（52 - 86.5%）、4b（57.7 - 79.4%）和4c（59.9 - 80.3%）在所有四种受试细菌中均能阻止生物膜形成，抑制率超过50%。发现抑制50%紫色杆菌素产生的4a、4b和4c的浓度分别为62.71、28.56和107.45μg/mL，从而证明这些化合物具有群体感应抑制活性。值得注意的是，我们之前的研究证明这些化合物对人类哺乳动物细胞Vero无细胞毒性。这一新颖的研究成果证明了基于四嗪的苯并噻唑具有抗菌、抗生物膜和群体感应抑制活性，有望作为发现高效抗生素的骨架，降低微生物耐药风险。
