5 documents found, page 1 of 1
Synthesis, activity, toxicity, and in silico studies of new antimycobacterial N...
Pais, João P.; Antoniuk, Olha; Pires, David; Delgado, Tiago; Fortuna, Andreia; Costa, Paulo J.; Anes, Elsa; Constantino, LuisTuberculosis (TB) is a disease that plagues the frailest members of society. We have developed a family of N-alkyl nitrobenzamides that exhibit promising antitubercular activities and can be considered a structural simplification of known inhibitors of decaprenylphosphoryl-β-D-ribofuranose 2′-oxidase (DprE1), an essential Mycobacterium tuberculosis (Mtb) enzyme and an emergent antitubercular target. Hereby, we ...
Nitrobenzoates and nitrothiobenzoates with activity against M. tuberculosis
Pais, João P.; Antoniuk, Olha; Freire, Raquel; Pires, David; Valente, Emília; Anes, Elsa; Constantino, LuisEsters of weak acids have shown improved antimycobacterial activity over the corresponding free acids and nitro benzoates in particular have previously shown to have a very intriguing activity. To expand the potential of nitro-derivatives of benzoic acid as antimycobacterial drugs and explore the effects of various structural features on the activity of these compounds, we have obtained a library of 64 derivati...
Esters of pyrazinoic acid are active against pyrazinamide-resistant strains of ...
Pires, David; Valente, Emília; Simões, Marta Filipa; Carmo, Nuno; Testa, Bernard; Constantino, Luis; Anes, ElsaPyrazinamide (PZA) is active against major Mycobacterium tuberculosis species (M. tuberculosis, M. africanum, and M. microti) but not against M. bovis and M. avium. The latter two are mycobacterial species involved in human and cattle tuberculosis and in HIV coinfections, respectively. PZA is a first-line agent for the treatment of human tuberculosis and requires activation by a mycobacterial pyrazinamidase to ...
Lipophilic pyrazinoic acid amide and ester prodrugs Stability, activation and a...
Simoes, Marta Filipa; Valente, Emilia; Rodriguez Gomez, M. Jose; Anes, Elsa; Constantino, LuisPyrazinamide (PZA) is active against M. tuberculosis and is a first line agent for the treatment of human tuberculosis. PZA is itself a prodrug that requires activation by a pyrazinamidase to form its active metabolite pyrazinoic acid (POA). Since the specificity of cleavage is dependent on a single bacterial enzyme, resistance to PZA is often found in tuberculosis patients. Esters of POA have been proposed in ...
Enhancement of the antituberculosis activity of weak acids by inhibitors of ene...
Gu, Peihua; Constantino, Luis; Zhang, YingMycobacterium tuberculosis is uniquely susceptible to weak acids compared with other mycobacteria or bacteria. The antituberculosis activity of the front-line drug pyrazinamide (PZA), a weak acid (pyrazinoic acid) precursor, can be enhanced by inhibitors of energy metabolism and anaerobiosis. Here, we investigated the effect of inhibitors of energy metabolism and anaerobiosis on weak acid activity against M. tu...