438190-39-7Relevant academic research and scientific papers
Novel thiazolidinedione-hydroxamates as inhibitors of Mycobacterium tuberculosis virulence factor Zmp1
?lachtová, Veronika,?ebela, Marek,Torfs, Eveline,Oorts, Lauren,Cappoen, Davie,Berka, Karel,Bazgier, Václav,Brulíková, Lucie
, (2019/11/28)
Zinc metalloprotease 1 (Zmp1) is an extracellular enzyme, which has been found essential for the intracellular survival and pathogenesis of Mycobacterium tuberculosis. In this work, we designed and synthesized a series of novel thiazolidinedione-hydroxamates and evaluated in silico their drug-likeness behavior. Then, their inhibitory properties towards a recombinant Zmp1 from Mycobacterium tuberculosis were analyzed by MALDI-TOF MS. Nine of the tested compounds were found to inhibit the enzymatic reaction more effectively than the generic metalloprotease inhibitor phosphoramidon. Furthermore, the synthesized thiazolidinedione-hydroxamate hybrids were evaluated for their in vitro antimycobacterial activity and acute cytotoxicity using whole-cell assays. Results showed that none of the hybrids exhibited acute cytotoxicity against RAW264.7 macrophages. Whereas extracellular antimycobacterial activity was limited, RAW264.7 macrophage infection results showed that a majority of the hybrids inhibited the intracellular growth of Mycobacterium tuberculosis at a concentration of 100 and 10 μM. The thiazolidinedione-hydroxamate compound 2n was considered to be the best candidate of the evaluated library.
Synthesis and aldose reductase inhibitory activity of 5-arylidene-2,4-thiazolidinediones
Bruno,Costantino,Curinga,Maccari,Monforte,Nicolo,Ottana,Vigorita
, p. 1077 - 1084 (2007/10/03)
Several (Z)-5-arylidene-2,4- hiazolidinediones were synthesized and tested as aldose reductase inhibitors (ARIs). The most active of the N-unsubstituted derivatives (2) exerted the same inhibitory activity of Sorbinil. The introduction of an acetic side chain on N-3 of the thiazolidinedione moiety led to a marked increase in lending inhibitory activi y, conducting to the discovery of a very potent ARI (4c), whose activity level (IC50 =0.1 μM) was in the same range of Tolrestat . Moreover, the corresponding methyl esters (3), devoid of any acidic functionality, showed appreciable inhibitory activity similar to that of the N-unsubstituted compounds. It was also found that the substitution pattern on the 5-benzylidene moiety markedly influenced the activity of N-unsubstituted 2,4-thiazolidinediones 2, compounds with substituents at the meta position being generally more effective than the para-substituted ones; however, this SAR was not evidenced in acetates 3 and acids 4. Copyright
