Exploration of the Antimicrobial Effects of Benzothiazolylthiazolidin-4-One and In Silico Mechanistic Investigation

Abstract

Background: Infectious diseases still affect large populations causing significant morbidity and mortality. Bacterial and fungal infections for centuries were the main factors of death and disability of millions of humans. Despite the progress in the control of infectious diseases, the appearance of resistance of microbes to existing drugs creates the need for the development of new effective antimicrobial agents. In an attempt to improve the antibacterial activity of previously synthesized compounds modifications to their structures were performed. Methods: Nineteen thiazolidinone derivatives with 6-Cl, 4-OMe, 6-CN, 6-adamantan, 4-Me, 6-adamantan substituents at benzothiazole ring were synthesized and evaluated against panel of four bacterial strains S. aureus, L. monocytogenes, E. coli and S. typhimirium and three resistant strains MRSA, E. coli and P. aeruginosa in order to improve activity of previously evaluated 6-OCF3-benzothiazole-based thiazolidinones. The evaluation of minimum inhibitory and minimum bactericidal concentration was determined by microdilution method. As reference compounds ampicillin and streptomycin were used. Results: All compounds showed antibacterial activity with MIC in range of 0.12–0.75 mg/mL and MBC at 0.25–>1.00 mg/mL The most active compound among all tested appeared to be compound 18, with MIC at 0.10 mg/mL and MBC at 0.12 mg/mL against P. aeruginosa. as well as against resistant strain P. aeruginosa with MIC at 0.06 mg/mL and MBC at 0.12 mg/mL almost equipotent with streptomycin and better than ampicillin. Docking studies predicted that the inhibition of LD-carboxypeptidase is probably the possible mechanism of antibacterial activity of tested compounds. Conclusion: The best improvement of antibacterial activity after modifications was achieved by replacement of 6-OCF3 substituent in benzothiazole moiety by 6-Cl against S. aureus, MRSA and resistant strain of E. coli by 2.5 folds, while against L. monocytogenes and S. typhimirium from 4 to 5 folds.

Thiazolidin-4-Ones as Potential Antimicrobial Agents: Experimental and In Silico Evaluation

“…Benzothiazole, a heterocyclic organic compound, and its derivatives have been reported to possess a wide range of biological activities such as antimicrobial [ 8 , 9 , 10 , 11 ], anti-inflammatory [ 12 , 13 ], antioxidant [ 14 , 15 ], analgesic [ 16 , 17 ], anticancer [ 18 , 19 , 20 ], antiviral [ 21 , 22 , 23 ], anti-HIV [ 24 , 25 ], antidiabetic [ 26 , 27 ], anticonvulsant [ 28 , 29 ], antimalarial [ 30 ], and antitubercular [ 31 , 32 ].…”

Benzothiazole and Chromone Derivatives as Potential ATR Kinase Inhibitors and Anticancer Agents

“…Benzothiazole is a heterocyclic organic compound with a wide range of biological activities such as antimicrobial [ 6 , 7 ], anti-inflammatory [ 8 , 9 ], antioxidant [ 10 , 11 ], analgesic [ 8 , 12 ], anticancer [ 13 , 14 , 15 , 16 ], antiviral [ 17 , 18 , 19 , 20 ], anti-HIV [ 21 , 22 ], antidiabetic [ 23 ], anticonvulsant [ 24 , 25 ], antimalarial [ 26 ], antitubercular [ 27 , 28 ] and kinase inhibitor [ 29 , 30 ]. It should be mentioned that some FDA-approved drugs involve a benzothiazole carrier scaffold ( Figure 1 ).…”

The Bioactivity of Thiazolidin-4-Ones: A Short Review of the Most Recent Studies

“…Among the thiazolidin-4-ones (111a, 111b) with trifluoromethoxy group, Compound 111a showed antibacterial activity at minimal inhibitory concentration of 100 µg/mL against S. aureus and Listeria monocytogenes strains. Slightly better activity was exhibited by their chlorosubstituted analogues (111c, 111d) against L. monocytogenes and P. aeruginosa resistant strain with MIC = 60 µg/mL [117,118]. It is worth to pay attention to Compound 109 (Figure 47) among the TZD derivatives, that exhibited good antibacterial as well as antifungal activity.…”