- Tytuł:
-
Adenozyno-5’-o-(n-acylosulfamoilowe) pochodne jako potencjalne leki przeciwgruźlicze
5’-o-[n-(acyl)sulfamoyl]adenosine derivatives as potential antituberculosis drugs - Autorzy:
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Kulik, K.
Baraniak, J. - Powiązania:
- https://bibliotekanauki.pl/articles/172072.pdf
- Data publikacji:
- 2016
- Wydawca:
- Polskie Towarzystwo Chemiczne
- Tematy:
-
leki przeciwgruźlicze
prątek gruźlicy
acyloadenylany
antituberculosis drugs
Mycobacterium tuberculosis
acyladenylates - Opis:
- Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis (TB), is the leading bacterial cause of infectious disease mortality. The current WHOapproved treatment for TB involves a three- or four-drug regimen comprising isoniazid, rifampin, pyrazinamide, and/or ethambutol for a minimum of 6 months. While these first-line agents remain useful in treating susceptible Mycobacterium tuberculosis strains, the emergence of multidrug resistant tuberculosis demands the development of new drugs [1]. Iron acquisition is an essential process for M. tuberculosis as well as almost all other microorganisms. However, this essential micronutrient is highly sequestered in a mammalian host. In response to iron starvation, Mtb produces small-molecule iron chelators, a pair of related peptidic siderophores known as mycobactin and carboxymycobactins that vary by the appended lipid residue termed siderophores [4, 5, 7, 8]. Because mycobactins are critical for growth and virulence of M. tuberculosis, they have emerged as attractive targets for the development of anti-TB agents [4]. Biosynthesis of mycobactin is initiated by the aryl acid adenylation enzyme MbtA which activates salicylic acid forming an acyladenylate intermediate (Sal- AMP). MbtA is also responsible for loading the acyladenylate intermediate onto the thiolation domain of MbtB-SH – the enzyme taking part in the next step of biosynthesis process [10]. Given the documented importance of many siderophores for virulence and lack of human aryl acid adenylation enzymes homologues, several analogues possessing stable linkers as bioisosteres of the labile acyl phosphate function have been synthesized as the potent enzyme inhibitors [13]. The initial lead compound 5’-O-[N- (salicyl)sulfamoyl]adenosine (Sal-AMS) has emerged as a promising inhibitor of MbtA and was shown to possess promising whole-cell activity toward M. tuberculosis.
- Źródło:
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Wiadomości Chemiczne; 2016, 70, 7-8; 455-472
0043-5104
2300-0295 - Pojawia się w:
- Wiadomości Chemiczne
- Dostawca treści:
- Biblioteka Nauki
Artykuł