The global increase in bacterial resistance poses a significant threat, jeopardizing the effectiveness of antibiotics. Therefore, the development of new and efficient antimicrobial agents is pre-dominant. Taking this into consideration, in the present study, we designed and reported the facile synthesis of two novel series benzothiazole–triazole and thiazolidinone-appended benzothiazole–triazole hybrids using a molecular hybridization approach in a one-pot process. The synthesized compounds were tested for microbial growth inhibition against bacterial and fungal strains. Among all the synthetics, compounds derived from methoxyphenyl and heteroaromatic ring substitutions exhibited promising inhibitory activity. The current investigation has emphasized that benzothiazole–triazole hybrids incorporating thiazolidinone can be a promising and potent category of molecules with potential biological activities. This sustainable and eco-friendly protocol involves the metal-free, catalyst-free synthesis of bioactive scaffolds, which merges broad tolerance for functional groups with a short reaction time, resulting in good to excellent yields.
