Background: The emergence of multi-drug resistant and extensively drug-resistant cases of
tuberculosis has lead to the search for new structural classes of anti-tuberculosis drugs. There are many
reports on antimycobacterial screening of compounds containing the 4-thiazolidinone moiety. The 5-
arylidene moiety in the 2-heteroarylimino-5-benzylidene-4-thiazolidinone scaffold plays an important
role in antimicrobial activity against Gram-positive and Gram-negative bacteria, yeasts and moulds.
Objective: To synthesize 2-thiazolylimino-5-arylidene-4-thiazolidinone derivatives, with different substituents
on the aryl ring, and evaluate their in vitro antimycobacterial activity against M. tb H37Rv.
Methods: The derivatives were synthesized by previously reported methods, and structures confirmed
by spectral data. Qikprop, the ADME prediction program was used in predicting pharmacokinetic
properties of the derivatives, which helped in designing and synthesis of novel and more
potent analogs. In vitro antimycobacterial activity against drug-sensitive M. tb H37Rv was performed
in BACTEC-460 TB radiometric system.
Results: The synthesis and antimycobacterial activities of 2-thiazolylimino-5-arylidene-4-thiazolidinone
derivatives have been reported. The chemical modifications not only altered the physicochemical
properties but also pharmacological activities. The compounds exhibited moderate to excellent in vitro
activity (88-99.7% inhibition) against M. tb H37Rv, and few demonstrated >99% inhibition at 6.25
μg/mL. The activity was considerably affected by various substituents and compounds with di- and trisubstitutions
on the aromatic ring of the 4-thiazolidinone were more active.
Conclusion: These preliminary but encouraging results indicate that 2-thiazolylimino-5-arylidene-4-
thiazolidinones are promising scaffolds for design and development of new molecules for antimycobacterial
activity. Several compounds were identified as novel and potential lead for design and synthesis
of new antimycobacterial agents.