Synthesis, Characterization, Antibacterial and Antioxidant Potency of NSubstituted- 2-Sulfanylidene-1,3-Thiazolidin-4-one Derivatives and QSAR Study
Authors: Brahmbhatt Harshad , Molnar Maja , Pavić Valentina , Rastija Vesna 
Published: December 2018

Background:

Rhodanine is known for its potential and important role in the medicinal
chemistry since its derivatives exhibit a wide range of pharmacological activities such as antibacterial,
antifungal, antidiabetic, antitubercular, anti-HIV, antiparasitic, antioxidant, anticancer, antiproliferative
and anthelmintic agents.

Objectives:

Since N-substituted rhodanine synthons are rarely commercially available, it is desirable
to develop a straightforward synthetic approach for the synthesis of these key building blocks.
The objective was to synthesize a series of rhodanine derivatives and to investigate their antimicrobial
and antioxidant activity. Also, in order to obtain an insight into their structure-activity relationship,
QSAR studies on the antioxidant activity were performed.

Methods:

1H and 13C FTNMR spectra were recorded on Bruker Avance 600 MHz NMR Spectrometer,
mass analysis was carried out on ESI+ mode by LC-MS/MS API 2000. 2,2-Diphenyl-1-
picrylhydrazyl radical scavenging activity (% DPPH) was determined in dimethylsulfoxide
(DMSO) as a solvent. The antibacterial activity was assessed against Bacillus subtilis, Staphylococcus
aureus (Gram positive) and Escherichia coli, Pseudomonas aeruginosa (Gram negative)
bacteria in terms of the minimum inhibitory concentrations (MICs) by a modified broth microdilution
method.

Results:

A series of N-substituted-2-sulfanylidene-1,3-thiazolidin-4-ones were synthesized and
characterized by 1H NMR, 13C NMR, FTIR, GC MS, LCMS/MS and C,H,N,S elemental analysis.
Most of the synthesized compounds showed moderate to excellent antibacterial activity (MIC values
from 125 μg/ml to 15.62 μg/mL) and DPPH scavenging activity (from 3.60% to 94.40%).
Compound 2-thioxo-3- (4-(trifluoromethyl)-phenyl)thiazolidin-4-one showed the most potent activity
against Escherichia coli (3.125 μg/mL), equivalent to antibiotic Amikacin sulphate and
against Staphylococcus aureus (0.097 μg/ml), 100 times superior then antibiotic Amikacin
sulphate. It has also shown a potent antioxidant activity (95% DPPH scavenging). Two best QSAR
models, obtained by GETAWAY descriptor R7p+, Balabans molecular connectivity topological
index and Narumi harmonic topological index (HNar), suggest that the enhanced antioxidant activity
is related to the presence of pairs of atoms higher polarizability at the topological distance 7,
substituted benzene ring and longer saturated aliphatic chain in N-substituents.

Conclusion:

A series of novel N-substituted-2-thioxothiazolidin-4-one derivatives were designed,
synthesized, characterized and evaluated for their antibacterial and antioxidant activity in vitro.
Majority of the compounds showed excellent antibacterial activity compared to ampicillin and few
of them have an excellent activity as compared to Chloramphenicol standard antibacterial drug.
The QSAR study has clarified the importance of presenting a pairs of atoms higher polarizability,
such as Cl and S at the specific distance, as well as the substituted benzene ring and a long saturated
aliphatic chain in N-substituents for the enhanced antioxidant activity of 2-sulfanylidene-1,3-
thiazolidin-4-one derivatives.