Discovery of 2-aryl and 2-pyridinylbenzothiazoles endowed with antimicrobial and aryl hydrocarbon receptor agonistic activities

•Sixteen functionalized benzothiazoles were evaluated as antimicrobial agents and as AhR modulators.•The benzothiazoles showed noticeable antimicrobial effects against Gram-positive and Gram-negative pathogens and against the yeast C. albicans.•Six benzothiazoles exhibited significant AhR agonist effects in a cell-based reporter gene assay.•Structure-activity relationship analysis exposed some relevant headings on the substituent's contributions to the studied biological effects.•Compound 12 displayed promising biocide activity and AhR agonism as well as an adequate ADMET profile and binding similarities with FICZ. [Display omitted] Benzothiazole is a privileged scaffold in medicinal chemistry present in diverse bioactive compounds with multiple pharmacological applications such as analgesic, anticonvulsant, antidiabetic, anti-inflammatory, anticancer and radioactive amyloidal imagining agents. We reported in this work the study of sixteen functionalized 2-aryl and 2-pyridinylbenzothiazoles as antimicrobial agents and as aryl hydrocarbon receptor (AhR) modulators. The antimicrobial activity against Gram-positive (S. aureus and M. luteus) and Gram-negative (P. aeruginosa, S. enterica and E. coli) pathogens yielded MIC ranging from 3.13 to 50 μg/mL and against the yeast C. albicans, the benzothiazoles displayed MIC from 12.5 to 100 μg/mL. All compounds showed promising antibiofilm activity against S. aureus and P. aeruginosa. The arylbenzothiazole 12 displayed the greatest biofilm eradication in S. aureus (74%) subsequently verified by fluorescence microscopy. The ability of benzothiazoles to modulate AhR expression was evaluated in a cell-based reporter gene assay. Six benzothiazoles (7, 8-10, 12, 13) induced a significant AhR-mediated transcription and interestingly compound 12 was also the strongest AhR-agonist identified. Structure-activity relationships are suggested herein for the AhR-agonism and antibiofilm activities. Furthermore, in silico predictions revealed a good ADMET profile and druglikeness for the arylbenzothiazole 12 as well as binding similarities to AhR compared with the endogenous agonist FICZ.