Guojun Pan

Inhibitor of the human telomerase reverse trancriptase (hTERT) gene promoter induces cell apoptosis via a mitochondrial-dependent pathway

Telomerase is aberrantly expressed in many cancers and plays an important role in the development of cellular immortality and oncogenesis, which makes it a potential cancer therapeutic target for drug discovery. Here, we constructed a firefly luciferase reporter driven by the human telomerase reverse trancriptase (hTERT) gene promoter to screen for inhibitory compounds. Compound 5c was discovered and shown to significantly inhibit the promoter activity of hTERT gene. Furthermore, five analogs of compound 5c were synthesized, and compound 8b was shown to be a more potent inhibitor of hTERT gene promoter activity and subsequent expression of hTERT mRNA and protein. The viability of HeLa cells was inhibited by a knockdown of hTERT gene expression, and the same effect was also observed by treating with compound 8b. Moreover, our results indicated that compound 8b induced apoptosis of HeLa cells, and activated caspase-9 and caspase-3 enzymes. Taken together, these results suggested that compound 8b down-regulates the expression of hTERT and induces mitochondrial-dependent apoptosis.

Total synthesis of I3,II8-biapigenin and ridiculuflavone A

The first total synthesis of I3,II8-biapigenin and ridiculuflavone A via the key steps of regioselective iodination, Sonogashira reaction, and rhodium-catalyzed oxidative coupling with the overall yields of 31% and 22%, respectively, was reported. The structures of the key intermediates for the two natural products were confirmed by single-crystal X-ray analysis.

Design, Synthesis and Primary Biological Evaluation of the Novel Antitumor Agent Indoline-3-One and Its Derivatives

Indolinone displays promising antitumor properties by inhibiting various kinase families. In this paper, we’d like to report the design, synthesis, and primary biological evaluation of the novel indoline-3-one and its derivatives. All the newly synthesized compounds including the novel compound 2-(4-(trifluoromethyl)benzylidene)indolin-3-one (5f) were characterized by 1H NMR and their antitumor activities were evaluated by using MTT method in HT-29, K562, and HepG2 cell lines. 2-(2-nitrobenzylidene)indolin-3-one (5d) demonstrated good antitumor activity against HT-29, K562, and HepG2 with an IC50 of 2.04 μM, 2.33 μM, 2.24 μM, respectively. 2-(4-(trifluoromethyl)benzylidene)indolin-3-one(5f) demonstrated good antitumor activity against K562 and HepG2 with an IC50 of 2.27 μM, 3.47 μM.