Heliyon (Oct 2024)
Molecular modelling and antimicrobial activity of newly synthesized benzothiazolo[3,2-a]pyrimidine clubbed thiazole derivatives
Abstract
A series of benzothiazolopyrimidine-thiazole conjugates 7, 8, and 9 were produced through the reactions of 8-acetylbenzothiazolopyrimidine-thiosemicarbazone compound 6 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 5 and its thiosemicarbazone compound 6, which were flat. The study of FMO's also showed that the substituted thiazole derivatives 7 and 8a-c have equivalent configurations of HOMO and LUMO, as well as exhibiting the least FMO's gap (ΔEH-L). 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 8c exhibited the strongest inhibition towards Gram-negative E. coli (MIC <29 μg/mL), while a valuable performance was observed towards S. typhimurium (MIC <132 μg/mL). Also, it displayed broad-spectrum activity with the least MIC versus C. albicans fungi (<207 μg/mL). In contrast, the conjugate 8b demonstrated selective efficacy against Gram + ve S. aureus and B. subtilis 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 via the SwissADME prediction. The data indicated that derivative 5 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.
