Synthesis and antitumor evaluation of fluoroquinolon C3 s-triazole oxadiazole methylsulfide derivatives of ofloxacin / 中国药学杂志

OBJECTIVE: To explore an efficient heterocyclic bioisostere as the C3 carboxylic group of antibacterial fluoroquinolones for further development of antitumor fluoroquinolones. METHODS: Using the s-triazole ring as an isosteric replacement of the C3 carboxylic group with another different heterocyclic ring, oxadiazole, as a modified group, new bis-(different azole) methylsulfide derivatives, 6-fluoro-7-(4-methyl-piperazin-1-yl)-1, 8-(2, 1-oxpropyl)-5-[5-(aryl-[1, 3, 4]-oxadiazol-2-methylsulfanyl)-4H-[1, 2, 4]-tri-azol-3yl]-quinolin-4(1H)-ones (6a-6j), were designed from ofloxacin (1). The in vitro antitumor activity of 6a-6j against three cancer cell lines was evaluated by MTT assay. RESULTS: Ten title compounds (6a-6j) ere synthesized and their structures were characterized by spectral data. They exhibited significantly higher in vitro antitumor potency than the parent compound ofloxacin. CONCLUSION: The heterocyclic ring, s-triazole, could be used as an efficient isostere of the C-3 carboxylic group for further development of antitumor fluoroquinolone candidates.

Molecular mechanism of ophiopogonin B induced cellular autophagy of human cervical cancer HeLa cells / 药学学报

This study is to investigate the antitumor activity of ophiopogonin B (OP-B). MTT assay, flow cytometric analysis, acridine orange staining, Lyso-Tracker Red staining and HeLa-GFP-LC3 transfect cells assay were used to detect the proliferation activity, apoptosis and autophagy of HeLa cells. The results showed that OP-B exerted potent antiproliferative activity on HeLa cells, the cell growth inhibition effect of OP-B was not due to apoptosis and OP-B could induce autophagy of HeLa cells. OP-B also induced the protein expression up-regulation of Beclin-1 and promoted LC3 I transformation LC3 II, which were representative proteins of autophagy. Furthermore, 3-MA, an inhibitor of autophagy, not only inhibited OP-B-mediated autophagy but also almost completely reversed the antiproliferative effect of OP-B, suggesting that the growth inhibition effect of OP-B was autophagy dependent. Western blotting demonstrated that OP-B inhibited the phosphorylation of Akt and its' downstream vital protein, such as mTOR and p70S6K. In addition, OP-B also induced the protein expression up-regulation of PTEN, which is a negative regulation protein for Akt/mTOR signaling pathway. However, OP-B did not affect the protein expression of total Akt. Collectively, the antitumor effects of OP-B were autophagy-dependent via repression Akt/mTOR signaling pathway. Therefore, OP-B is a prospective inhibitor of Akt/mTOR and may be used as an alternative compound to treat cervical carcinoma.

Synergistic antitumor effects of tanshinone II A in combination with cisplatin via apoptosis in the prostate cancer cells / 药学学报

Treatment with the combination of Chinese herbs and cytotoxic chemotherapies showed a higher survival rate in clinical trials. In this report, the results demonstrated that the tanshinone II A, a key component of Salvia miltiorrhiza bunge, when it is combined with the cytotoxic drug cisplatin showed synergistic antitumor effects on human prostate cancer PC3 cells and LNCaP cells in vitro. Antiproliferative effects were detected with MTT assay. Cell cycle distribution and apoptosis were detected by flow cytometer. Protein expression was detected by Western blotting. The intracellular concentration of cisplatin was detected by high performance liquid chromatography. The results demonstrated that tanshinone II A significantly enhanced the antiproliferative effects of cisplatin on human prostate cancer PC3 cells and LNCaP cells with the increase of the intracellular concentration of cisplatin. These effects were correlated with cell cycle arrested at S phase and cell apoptosis. The apoptosis might be achieved through death receptor pathway and mitochondrial pathway. Furthermore, the Bcl-2 family members were also involved in this apoptotic process. Collectively, these results indicated that the combination of tanshinone II A and cisplatin had a better treatment effect in vitro not only on androgen-dependent LNCaP cells but also on androgen-independent PC3 cells.

Synthesis and antibacterial activity of 3-(5-substituted phenyl-1,3,4 oxadiazole-2-yl-methylenethio)-5-pyridin-3-yl-1,2,4 triazole-4-yl-amines / 药学学报

<p><b>AIM</b>To study on synthesis and antibacterial activity evaluation of polyheterocycles.</p><p><b>METHODS</b>The condensation of 4-amino-3-pyridin-3-yl-4H-[1,2,4] triazole-5-thiol with 2-chloromethyl-5-substituted phenyl-[1,3,4] oxadiazoles gave the corresponding title heterocycle amines, and the in vitro antibacterial activity was primarily evaluated by the method of cup-plate diffusion solution.</p><p><b>RESULTS</b>Twelve novel compounds were synthesized, and their structures were confirmed by IR, 1H NMR, MS and element analysis. Biological screening results demonstrated that most of the compounds prepared showed good antibacterial activity.</p><p><b>CONCLUSION</b>Oxadiazoles incorporting pyridyl triazole ring may be a pharmacophor structure in the molecule for developing antibacterial candidate drugs.</p>

Synthesis and antibacterial activity of 2-(3-pyridyl)-5-((5-aryl-1,3,4-oxadiazol-2-yl) methylenethio)-1,3,4-oxadiazoles / 药学学报

<p><b>AIM</b>Studies on synthesis and antibacterial activity of new heterocycles.</p><p><b>METHODS</b>The cyclocondensation of [(3-pyridyl)-1,3,4-oxadiazol-2-yl] thio acetic acid with various aroyl hydrazines in the presence of POCl3 and xylene gave the corresponding titled compounds, and the in vitro antibacterial activity was primarily evaluated by the method of cupplate diffusion solution.</p><p><b>RESULTS</b>Sixteen novel titled compounds were synthesized, their structures were confirmed by IR, 1HNMR, MS and elemental analysis. Biological screening results demonstrated that most of the compounds prepared displayed potential antibacterial activity.</p><p><b>CONCLUSION</b>Oxadiazoles incorporting pyridyl oxadiazole ring may be usefully antibacterial candidate drugs.</p>