Molecular modelling and antimicrobial activity of newly synthesized benzothiazolo[3,2-]pyrimidine clubbed thiazole derivatives.

A series of benzothiazolopyrimidine-thiazole conjugates , , and were produced through the reactions of 8-acetylbenzothiazolopyrimidine-thiosemicarbazone compound with chloroacetone, (un)substituted phenacyl chlorides, and ethyl chloroacetate, respectively. Based on DFT study, the synthesized conjugates had a twisted shape, except for the parent benzothiazolopyrimidine and its thiosemicarbazone compound , which were flat. The study of FMO's also showed that the substituted thiazole derivatives and have equivalent configurations of HOMO and LUMO, as well as exhibiting the least FMO's gap (ΔE). The antimicrobic activeness of the constructed derivatives has been assessed against the two Gram's types of bacteria and fungi using the broth microdilution method. The benzothiazolopyrimidine-thiazole conjugate exhibited the strongest inhibition towards Gram-negative (MIC <29 μg/mL), while a valuable performance was observed towards (MIC <132 μg/mL). Also, it displayed broad-spectrum activity with the least MIC fungi (<207 μg/mL). In contrast, the conjugate demonstrated selective efficacy against Gram + ve and bacteria (MIC <40 and < 47 μg/mL, respectively). Besides, molecular docking of these benzothiazolopyrimidine derivatives with the PDB: 2XCT protein carried out to discover their binding types, RMSD, binding scores, and interactions pocket for each derivative, including a drug reference. Furthermore, their physicochemical-pharmacokinetic profile has estimated the SwissADME prediction. The data indicated that derivative demonstrated constructive pharmacokinetics (M. Wt. 269.28), lipophilicity (Log Po/w = 1.45), and TPSA = 103.47, which foretold high (GI) absorption and good bioavailability = 0.55 without interrupting Lipinski's rules.