当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Cloning, characterization, and inhibition studies of a β-carbonic anhydrase from Leishmania donovani chagasi, the protozoan parasite responsible for leishmaniasis.

Cloning, characterization, and inhibition studies of a β-carbonic anhydrase from Leishmania donovani chagasi, the protozoan parasite responsible for leishmaniasis.

Abstract：

:Leishmaniasis is an infection provoked by protozoans belonging to the genus Leishmania. Among the many species and subsepecies of such protozoa, Leishmania donovani chagasi causes visceral leishmaniasis. A β-carbonic anhydrase (CA, EC 4.2.1.1) was cloned and characterized from this organism, denominated here LdcCA. LdcCA possesses effective catalytic activity for the CO2 hydration reaction, with kcat of 9.35 × 10(5) s(-1) and kcat/KM of 5.9 × 10(7) M(-1) s(-1). A large number of aromatic/heterocyclic sulfonamides and 5-mercapto-1,3,4-thiadiazoles were investigated as LdcCA inhibitors. The sulfonamides were medium potency to weak inhibitors (KI values of 50.2 nM-9.25 μM), whereas some heterocyclic thiols inhibited the enzyme with KIs in the range of 13.4-152 nM. Some of the investigated thiols efficiently inhibited the in vivo growth of Leishmania chagasi and Leishmania amazonensis promastigotes, by impairing the flagellar pocket and movement of the parasites and causing their death. The β-CA from Leishmania spp. is proposed here as a new antileishmanial drug target.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Syrjänen L,Vermelho AB,Rodrigues Ide A,Corte-Real S,Salonen T,Pan P,Vullo D,Parkkila S,Capasso C,Supuran CT

doi

10.1021/jm400939k

subject

Has Abstract

pub_date

2013-09-26 00:00:00

pages

7372-81

issue

18

eissn

0022-2623

issn

1520-4804

journal_volume

56

pub_type

杂志文章

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