The World Health Organization lists tuberculosis among the top 3 leading causes of death from a single infectious agent, and reported cases of multidrug-resistant tuberculosis (MDR-TB) are on the rise. In an attempt to improve MDR-TB drug-directed therapy, we synthesized 11 4-substituted piperazine derivatives of 3-hydroxy-6-methyl-4H -pyran-4-one pharmacophore by reacting 5-hydroxy-2-methyl- 4H-pyran-4-one with suitable piperazine derivatives under Mannich reaction conditions. Inhibitory effects of the 11 compounds on Escherichia coli DNA gyrase were evaluated via DNA gyrase supercoiling assay. The minimum inhibitory concentrations . . . (MIC) of the 11 compounds and 41 compounds from our previous studies against Mycobacterium tuberculosis H37RV were assessed, in vitro, by a broth dilution method. To determine the interaction pattern between active site amino acids and all 52 compounds, homology modeling for the construction of M. tuberculosis DNA gyrase B subunit was performed, followed by a docking study. The data presented here could prove useful in future studies on interaction field analysis and high throughput virtual screening of the derivatives of the 3-hydroxy-6-methyl-4H -pyran-4-one pharmacophore toward the development of more clinically applicable compounds
Daha fazlası
Daha az
A series of 3-hydroxy-6-methyl-2-((4-substitutedpiperazin-1-yl)methyl)-4H-pyran-4-one structured compounds were synthesized by reacting 5-hydroxy-2-methyl-4H-pyran-4-one with suitable piperazine derivatives using Mannich reaction conditions. Antibacterial activities of the compounds for E. coli, S. paratyphi, S. flexneri, E. gergoviae, and M. smegmatis were assessed in vitro by using broth dilution for determination of the minimum inhibitory concentration (MIC). In addition, their inhibitory effects over DNA gyrase enzyme were evaluated using a DNA gyrase supercoiling assay. Among the synthesized compounds; compound 7 showed a 4 &am . . .p;#956;g/mL MIC value for M. smegmatis, whereas the other compounds demonstrated moderate to high activity. Those tested in the supercoiling assay had at best a very mild inhibition of the enzyme. This series deserves further attention for testing over Mycobacterium species and topoisomerase II inhibition to develop new lead drugs
Daha fazlası
Daha az
New series of [(2-chloroethyl)ureido] benzoic acids (compounds 3-8) and nitric oxide releasing derivatives of [(2-chloroethyl)ureido] benzoic acid esters (compounds 9-14) were synthesized as potential anti-cancer agents. These compounds were screened for their anti-proliferative activities on A549 (human lung carcinoma) cells and for their cytotoxic effects on L929 (mouse fibroblast) cells. The compounds 3-8 exhibited mild cytotoxic effects on L929 cells (cell viability from 100% to 85% – 90% only) whereas they had very little antiproliferative activities towards A549 lung carcinoma cells. On the other hand, compounds 10, . . .11, and 13 had some growth inhibition activity in A549 (human lung carcinoma) cells. Among them, compounds 11 and 13 exhibited better anti-proliferative activities towards A549 cells, but also appeared to be cytotoxic towards L929 cells. In this group, the compound 10 with (1-(2-nitrooxyethyl)-3-[(2-chloroethyl)ureido]benzoate) structure appeared to have very weak anti-neoplastic activity towards A549 cells, with very little cytotoxic activity towards fibroblasts at physiological concentrations. Therefore, this compound is a better candidate for a potential anti-cancer therapy for non-small cell lung carcinomas. However, further studies are required in order to show applicability and effectiveness in animal models for this type of cancer
Daha fazlası
Daha az
...
6698 sayılı Kişisel Verilerin Korunması Kanunu kapsamında yükümlülüklerimiz ve çerez politikamız hakkında bilgi sahibi olmak için alttaki bağlantıyı kullanabilirsiniz.
