Sammanfattning

The Rv3588c gene product of Mycobacterium tuberculosis, a beta-carbonic anhydrase (CA, EC 4.2.1.1) denominated here mtCA 2, shows the highest catalytic activity for CO(2) hydration (k(cat) of 9.8 x 10(5) s(-1), and k(cat)/K(m) of 9.3 x 10(7) M(1) s(1)) among the three beta-CAs encoded in the genome of this pathogen. A series of sulfonamides/sulfamates was assayed for their interaction with mtCA 2, and some diazenylbenzenesulfonamides were synthesized from sulfanilamide/metanilamide by diazotization followed by coupling with amines or phenols. Several low nanomolar mtCA 2 inhibitors have been detected among which acetazolamide, ethoxzolamide and some 4-diazenylbenzenesulfonamides (K(I)s of 9-59 nM). As the Rv3588c gene was shown to be essential to the growth of M. tuberculosis, inhibition of this enzyme may be relevant for the design of antituberculosis drugs possessing a novel mechanism of action. (C) 2009 Elsevier Ltd. All rights reserved.

Nyckelord

Carbonic anhydrase; Mycobacterium tuberculosis; Rv3588c; Sulfonamide; Enzyme inhibitor

Publicerad i

Bioorganic and Medicinal Chemistry Letters
2009, Volym: 19, nummer: 23, sidor: 6649-6654
Utgivare: PERGAMON-ELSEVIER SCIENCE LTD

SLU författare

• Mowbray, Sherry

  • Institutionen för molekylärbiologi, Sveriges lantbruksuniversitet
    

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Organisk kemi


Publikationens identifierare

DOI: https://doi.org/10.1016/j.bmcl.2009.10.009

Permanent länk till denna sida (URI)

https://res.slu.se/id/publ/49154