Tandem synthesis and antibacterial screening of novel thieno[2,3-b]thiophene-linked bis(thiazole) hybrids

Abstract

We reported herein a facile tandem synthesis of new bis(thiazoles) utilizing the appropriate thieno[2,3-b]thiophene-linked bis(α-bromoketones). Thus, two equivalents of each of the appropriate acetonitriles were reacted with phenyl isothiocyanate and potassium hydroxide in DMF under stirring at rt for 6 h. To the prior mixture, one equivalent of the appropriate bis(α-bromoketones) was added and stirring was continued for 8 h to give the target bis(thiazoles). Furthermore, we examined the synthesis of new bis(thiazoles) linked to different heterocyclic units. These hybrids were prepared using a similar tandem protocol and utilizing the appropriate acetonitriles, linked to thiazole, benzothiazole, benzoxazole or benzimidazole units. The in vitro antibacterial efficacy of the new hybrids was assessed using the reference Ciprofloxacin (MIC values of 2.7 µM). New hybrids linked to benzoxazole units displayed the best antibacterial efficacy against S. aureus, S. mutans, E. coli, and K. pneumonia strains with MIC values of 1.6–3.3 µM.

Graphical Abstract

Keywords:

• Bis(thiazole) hybrids
• cyanoketene N,S-acetal
• in vitro antibacterial screening
• tandem synthesis
• thieno[2,3-b]thiophene