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Current Topics in Medicinal Chemistry


ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Research Article

Substituted 6,7-dimethoxy-5-oxo-2,3,5,9b-tetrahydrothiazolo[2,3-a]isoindole- 3-1,1-dioxide Derivatives with Antimicrobial Activity and Docking Assisted Prediction of the Mechanism of their Antibacterial and Antifungal Properties

Author(s): Athina Geronikaki*, Victor Kartsev, Phaedra Eleftheriou, Anthi Petrou, Jasmina Glamočlija, Anna Ciric and Marina Soković

Volume 20, Issue 29, 2020

Page: [2681 - 2691] Pages: 11

DOI: 10.2174/1568026620666200922114735

Price: $65


Background: Although a great number of the targets of antimicrobial therapy have been achieved, it remains among the first fields of pharmaceutical research, mainly because of the development of resistant strains. Docking analysis may be an important tool in the research for the development of more effective agents against specific drug targets or multi-target agents 1-3.

Methods: In the present study, based on docking analysis, ten tetrahydrothiazolo[2,3-a]isoindole derivatives were chosen for the evaluation of the antimicrobial activity.

Results: All compounds showed antibacterial activity against eight Gram-positive and Gram-negative bacterial species being, in some cases, more potent than ampicillin and streptomycin against all species. The most sensitive bacteria appeared to be S. aureus and En. Cloacae, while M. flavus, E. coli and P. aeruginosa were the most resistant ones. The compounds were also tested for their antifungal activity against eight fungal species. All compounds exhibited good antifungal activity better than reference drugs bifonazole (1.4 – 41 folds) and ketoconazole (1.1 – 406 folds) against all fungal species. In order to elucidate the mechanism of action, docking studies on different antimicrobial targets were performed.

Conclusion: According to docking analysis, the antifungal activity can be explained by the inhibition of the CYP51 enzyme for most compounds with a better correlation of the results obtained for the P.v.c. strain (linear regression between estimated binding Energy and log(1/MIC) with R 2 =0.867 and p=0.000091 or R 2 = 0.924, p= 0.000036, when compound 3 is excluded.

Keywords: Antimicrobial activity, Molecular docking studies, Strains, Drug, Antifungul activity, E. coli.

Graphical Abstract
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