Synthesis of new 4-anilinoquinazoline analogues and evaluation of their EGFR inhibitor activity / 药学学报

Thirteen of 4-anilinoquinazoline derivatives with imine groups at position 6 of quinazoline ring were synthesized and their antitumor activities were evaluated by MTT assay and Western blotting analysis. Among these compounds, 13a-131 were reported first time. The MTT assay was carried out on three human cancer cell lines (A549, HepG2 and SMMC7721) with EGFR highly expressed. Among the tested compounds, 13i and 13j exhibited notable inhibition potency and their IC50 values on three cell lines were equivalent to or less than those of gefitinib. Compound 14, without imine group substituted, displayed excellent inhibitor potency only on A549 cell line. Compounds 14 and 13j were chosen to perform Western blotting analysis on A549. The results showed that both of the compounds could inhibit the expression level of phosphorylated EGFR remarkably. It was concluded that the inhibitor potency of compound 14 was almost equivalent to that of gefitinib and the inhibitor potency of 13j was better than that of gefitinib.

Modulating autophagy: a strategy for cancer therapy / 癌症

Autophagy is a process in which long-lived proteins, damaged cell organelles, and other cellular particles are sequestered and degraded. This process is important for maintaining the cellular microenvironment when the cell is under stress. Many studies have shown that autophagy plays a complex role in human diseases, especially in cancer, where it is known to have paradoxical effects. Namely, autophagy provides the energy for metabolism and tumor growth and leads to cell death that promotes tumor suppression. The link between autophagy and cancer is also evident in that some of the genes that regulate carcinogenesis, oncogenes and tumor suppressor genes, participate in or impact the autophagy process. Therefore, modulating autophagy will be a valuable topic for cancer therapy. Many studies have shown that autophagy can inhibit the tumor growth when autophagy modulators are combined with radiotherapy and/or chemotherapy. These findings suggest that autophagy may be a potent target for cancer therapy.

Changes of adenylate cyclase on cerebral regions related to mophine dependence in rats / 法医学杂志

OBJECTIVE@#To observe the changes of adenylate cyclase(AC) on cerebral regions related to morphine dependence in rats and investigate the relationship between the enzymological changes and the mechanism of morphine dependence.@*METHODS@#The technique of enzyme-histochemistry was used to detect the variations of AC of special seven cerebral regions including frontalis cortex, lenticula, corpus amygdaloideun, substantia nigra, hippocampus, periaqueductal gray and locus coerleus in morphine dependent rats. The enzymological changes were observed by optical microscope. Changes of gray degree of these cerebral regions were also observed by using the image analysis system.@*RESULTS@#Compared with those in control group, the contents of AC in morphine dependent groups were increased.@*CONCLUSION@#The contents of AC are increase in those regions. The mechanism of morphine dependence close related to the increasing of AC. The correlation of the mechanism of morphine dependence and up-regulation of AC/cAMP-PKA system is discussed.

Isolation and structure identification of chemical constituents from the seeds of Descurainia sophia (L.) Webb ex Prantl / 药学学报

<p><b>AIM</b>To isolate and determine the structures of chemical constituents from the seeds of Descurainia sophia (L.) Webb ex Prantl.</p><p><b>METHODS</b>The chemical constituents were extracted from the seeds of Descurainia sophia (L.) Webb ex Prantl with 75% ethanol and purified by polyamide, silica gel, RP-C18 and Sephadex LH-20 on column chromatography. Chemical methods and spectroscopic methods, such as 1H and 13CNMR, HSQC, HMBC and TOCSY spectra were used for the structural identification.</p><p><b>RESULTS</b>Fifteen compounds were obtained. Twelve of them were identified as quercetin-3-O-beta-D-glucopyranosyl-7-O-beta-gentiobioside (I), kaempferol-3-O-beta-D-glucopyranosyl-7-O-beta-gentiobioside (II), isorhamnetin-3-O-beta-D-glucopyranosyl-7-O-beta-gentiobioside (III), quercetin-7-O-beta-gentiobioside (IV), kaempferol-7-O-beta-gentiobioside (V), isorhamnetin-7-O-beta-gentiobioside (VI), quercetin-3,7-di-O-beta-D-glucopyranoside (VII), kaempferol-3, 7-di-O-beta-D-glucopyranoside (VIII), isorhamnetin-3, 7-di-O-beta-D-glucopyranoside (IX), kaempferol-3-O-beta-D-glucopyranosyl-7-O-[(2-O-trans-sinnapoyl)-beta-D- glucopyranosyl(1-->6)]-beta-D-glucopyranoside) (X), sinapic acid ethyl ester (XI) and 3, 4, 5-trimethoxyl-cinnamic acid (XII).</p><p><b>CONCLUSION</b>Compounds X and VI are new compounds. IV, V, VII, VIII and IX were isolated from Cruciferae family for the first time. I, II, III were obtained from Descurania genus and XI, XII from D. sophia for the first time.</p>