Microwave-assisted Synthesis and Docking Studies of Phenylureas as Candidates for the Drug Design Against the Biological Warfare Agent Yersinia Pestis

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F20%3A50021377" target="_blank" >RIV/62690094:18470/20:50021377 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.eurekaselect.com/article/99538" target="_blank" >https://www.eurekaselect.com/article/99538</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.2174/1570180816666190710144212" target="_blank" >10.2174/1570180816666190710144212</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Microwave-assisted Synthesis and Docking Studies of Phenylureas as Candidates for the Drug Design Against the Biological Warfare Agent Yersinia Pestis

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Microwave-assisted Synthesis and Docking Studies of Phenylureas as Candidates for the Drug Design Against the Biological Warfare Agent Yersinia Pestis

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30107 - Medicinal chemistry

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Letters in drug design &amp; discovery

ISSN

1570-1808

e-ISSN

1875-628X

Svazek periodika

17

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

AE - Spojené arabské emiráty

Počet stran výsledku

7

Strana od-do

633-639

Kód UT WoS článku

000534606200012

EID výsledku v databázi Scopus

2-s2.0-85083165171