Aim and Objective:
The magic scaffolds rhodanine and thiazolidine are very important
heterocyclic compounds in drug design and discovery. Those are important heterocyclic
compounds that have attracted a great deal of attention due to the fact that they exhibit a variety of
bioactivities including antibacterial, antifungal, antiviral, antimalarial, and anti-inflammatory
activities. These agents often exhibit selective toxicity. The goal of this study was molecular
docking, green and solvent-free efficient synthesis of a new series of hetero/aromatic substituted
rhodanine and thiazolidine analogues and then investigation of their antimicrobial activity.
Materials and Methods:
To a mixture of TZD or rhodanine (1 mmol) in the presence of ionic
liquid ChCl/urea, various aldehyde (1 mmol) was added. After completion of the reaction, obtained
crude compound was collected by filtration and products were recrystallized from ethanol. The
binding-free energy between all synthesized compounds with 3EEJ protein (C. glabrata enzyme)
were obtained by molecular docking studies. These compounds were evaluated using microdilution
method against (ATCC 6538) and (ATCC 12228) Gram-negative, (ATCC 8739) and (ATCC 9027)
as Gram-positive and (ATCC 1012), (ATCC 339), C. (ATCC 1057), (ATCC 503), (ATCC 340)
and (ATCC 194) as fungi.
Results:
All of the acceptable products were determined by 1H NMR, 13C NMR, Mas and FT-IR
spectroscopy. The binding-free energy between compounds 10a and 10b with 3EEJ protein were
found to be -8.08 kcal/mol and -8.15 kcal/mol, respectively. These compounds having a
heteroaromatic ring attached to the TZD or rhodanine core showed excellent antimicrobial activity
with MIC values of 0.25-8 μg/mL (compound 10a) and 0.5-16 μg/mL (compound 10b) against the
most tested fungi strains, Gram-positive and Gram-negative bacteria.
Conclusion:
A convenient and rapid method has been developed for the synthesis of rhodanine and
thiazolidine-2,4-dione (TZD) derivatives as efficient antimicrobial agents using a Deep Eutectic
Ionic Liquids (DEILs) choline chloride urea under solvent-free condition. Among the newly
synthesized compounds, (Z)-5-((quinoxalin-3-yl) methylene) thiazolidine-2, 4-dione (10a) and (Z)-
5- ((quinoxalin-3-yl) methylene)-2-thioxothiazolidin-one (10b) exerted the promising effect and
these compounds can be considered to be further probed as inhibitors of cgDHFR enzyme.
Synthesis, characterization, antimicrobial activity and molecular docking studies of combined pyrazol-barbituric acid pharmacophores
