Background: Studies on anti-inflammatory and antimicrobial agents remains a
challenging and important area in medicinal chemistry research due to more toxic and rapid
development of resistance against first effective drugs. In search of novel anti-inflammatory
and antimicrobials agents, bisthiourea derivatives of dipeptide conjugated to 6-fluoro-3-
(piperidin-4-yl)benzo[d]isoxazole were synthesized.
Methods: The peptides were synthesized by solution phase method and conjugated to 6-
fluoro-3-(piperidin-4-yl)benzo[d]isoxazole using 1-ethyl-3-(3-dimethyl aminopropyl)carbodiimide
(EDCI)/hydroxybenzotriazole (HOBt) as a coupling agent and N-methylmorpholine
(NMM) as a base. The protecting group, 2-chlorobenzyloxycarbonyl (2-ClZ) and tertbutyloxycarbonyl
(Boc) were deblocked and further reacted with substituted phenyl isothiocyanates
to obtain bisthiourea derivatives.
Results: The molecules 1-24 were examined for their in vitro anti-inflammatory activity by
employing human erythrocyte suspension test and it was found that the IC50 values of 9, 12,
21 and 24 were lower than the IC50 of standard references indomethacin and ibuprofen. Further,
all the molecules were also evaluated for their in vitro antibacterial and antifungal activities
against various pathogens of human origin by agar well diffusion method. In addition,
binding interaction of active molecules (7-12 and 19-24) was performed on active site
of cyclooxygenase-2 (COX-2) and Staphylococcus aureus (SA) TyrRS showing good binding
Conclusion: Molecular docking result, along with the biological assay data, revealed that
the compounds containing electron withdrawing group (F) on phenyl ring of thiourea moiety
were potential anti-inflammatory and antimicrobial agents.