Synthesis and evaluation of linearly fused thiadiazolocoumarins as prospects with broad-spectrum bioactivity

Abstract

Various pharmacological properties of coumarins brought them under light among the heterocyclics. Also, coumarin derivatives still approve of their importance in the medical field as a valuable building block to elicit further derivatives with diverse, potent, and interesting biological activities. Moreover, the numerous biological actions of thiadiazole-based compounds contribute to the notion of this unique synthesis of linearly fused thiadiazolocoumarins using the molecular hybridization method. This work reported the novel synthesis of seven linearly fused thiadiazolocoumarins, including Precursor N-III and TDA1-TDA6. These derivatives were characterized by their physicochemical properties and through spectrophotometric tools, including FTIR, 1H NMR, and 13C NMR. Also, their pharmacokinetics were predicted using computer-based studies by the SwissADME and PreADMET programs. Furthermore, the derivatives were checked for several biological activities, including anticancer, biosafety, anti-oxidative stress, anti-inflammatory, antimicrobial, normal flora safety, and antidiabetic activities. According to the results, TDA3 showed the greatest anticancer activity against the examined cancer cell lines, with the highest cellular biosafety. TDA3 and TDA4 showed higher anti-oxidative stress activity than the other derivatives. All the prepared derivatives showed significant inflammation-inhibitory activity toward the LOX-5 enzyme while showing poor activity towards COX enzymes. According to antimicrobial activity, TDA4 exhibited the greatest anti-gram-negative activity and also showed the best safety toward the examined normal flora. TDA1 exhibited promising activity against anaerobic bacteria, while Precursor N-III, TDA3, and TDA4 showed significant antifungal activity. Finally, TDA1 demonstrated moderate antidiabetic activity, which was the greatest activity among the other derivatives. The authors concluded from the gathered results that the linearly fused thiadiazolocoumarins represent key structures for developing compounds with versatile bioactivities.