Background: Bubonic plague is amongst the diseases with the highest potential for being
used in biological warfare attacks today. This disease, caused by the bacterium Yersina pestis, is
highly infectious and can achieve 100% of fatal victims when in its most dangerous form. Besides,
there is no effective vaccine, and the chemotherapy available today against plague is ineffective if
not administered at the beginning of the infection.
Objective: Willing to contribute for changing this reality we propose here new phenylureas as candidates
for the drug design against plague meant to target the enzyme dihydrofolate reductase from
Y. pestis (YpDHFR).
Methods: Seven phenylureas, four of them new, were synthesized, following synthetic routes
adapted from procedures available in the literature, and using microwave irradiation. After, they
were submitted to docking studies inside YpDHFR and human DHFR (HssDHFR) in order to check
their potential as selective inhibitors.
Results: Our results revealed four new phenylureas and a new synthetic route for this kind of molecule
using microwave irradiation. Also, our docking studies showed that these compounds are capable
of binding to both HssDHFR and YpDHFR, with U1 - U4 and U23 showing more selectivity for
HssDHFR and U7, U8 being more selective towards YpDHFR.
Conclusion: We reported the synthesis with good yields of seven phenylureas, following a simple
and clean alternative synthetic route using microwave irradiation. Further molecular docking studies
of our compounds suggested that two are capable of binding more selectivity to YpDHFR, qualifying
as potential candidates for the drug design of new drugs against plague.