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.
Molecular Targeting of VEGF with a Suramin Fragment–DOCA Conjugate by Mimicking the Action of Low Molecular Weight Heparins