Entity

Time filter

Source Type


Patent
Xinjiang Huashidan Phar Maceutical Research Co. | Date: 2012-11-26

Disclosed in the present invention are a bis--carboline compound and a preparation method, a pharmaceutical composition and the use thereof. In particular, the bis--carboline compound and a pharmaceutical salt thereof are described as general formula I, and the bis--carboline compound is prepared through the condensation of -carboline intermediate and dihaloalkane. Also disclosed in the present invention are a pharmaceutical composition comprising an effective dose of the bis--carboline compound as shown in formula I and a pharmaceutically acceptable carrier, and the use of the bis--carboline compound in preparing drugs resistant to tumours such as melanoma, stomach cancer, lung cancer, breast cancer, kidney cancer, liver cancer, oral epidermoid carcinoma, cervical cancer, ovarian cancer, pancreatic cancer, prostate cancer, and colon cancer.


Guo L.,Shihezi University | Guo L.,Xinjiang Huashidan Pharmaceutical Research Co. | Cao R.,Sun Yat Sen University | Fan W.,Xinjiang Huashidan Pharmaceutical Research Co. | And 2 more authors.
Gaodeng Xuexiao Huaxue Xuebao/Chemical Journal of Chinese Universities | Year: 2016

A series of novel bivalent β-carbolines with a spacer of three to ten methylene units between the 7-oxygen was synthesized and characterized by nuclear magnetic resonance(NMR) and mass spectrometry(MS). The antitumor activities against Bel-7402, 786-0, BGC-823, A375, 769-P and MCF7 cell lines in vitro were investigated by MTT method. The results demonstrated that compounds 4c, 4k and 4r were almost inactive against all tumor cell lines, compounds 4g and 4o displayed significant cytotoxic activities with IC50 value of lower than 10 μmol/L against all tumor cell lines. Most compounds displayed good and selective cytotoxic activities against HT-29 and Blu-87 cell lines. Primary structure-activity relationships(SARs) analysis indicated that the length of the spacer affected cytotoxic activities in vitro, and 8-10 methylene units were more favorable. Moreover, n-butyl or i-butyl substituents in position-9 of β-carboline facilitated the antitumor potencies. © 2016, Higher Education Press. All right reserved.


Guo L.,Xinjiang Huashidan Pharmaceutical Research Co. | Cao R.,Xinjiang Huashidan Pharmaceutical Research Co. | Cao R.,Sun Yat Sen University | Fan W.,Xinjiang Huashidan Pharmaceutical Research Co. | Ma Q.,Xinjiang Huashidan Pharmaceutical Research Co.
Gaodeng Xuexiao Huaxue Xuebao/Chemical Journal of Chinese Universities | Year: 2014

In order to search for novel candidate compounds endowed with better antitumor activities and less neurotoxicities, a series of harmine derivatives were synthesized by modiflcation of position 2, 7 and 9 of β-carboline nucleus through N9-alkylated, C7-demethylated and C7-phenolic hydroxyl alkylated. C7-demethylation compounds could be easily obtained from the N9-alkylated derivatives using acetic acid and hydrobromic acid as reaction solvent, but N9-arylted derivatives couldn't get the demethylation compounds in the same way. The N2-quaternarized compounds(4a, 4b, 8a and 8b) were prepared from demethylation compounds (3a, 3b, 7a and 7b) by the addition of benzyl bromide in refluxing ethyl acetate. Eleven target compounds were synthesized and characterized by 1H NMR, 13C NMR, IR, MS and elemental analysis. All the target compounds were tested for cytotoxic activity against six cancer cell lines including Bel-7402, 786-0, BGC-823, A375, 769-P and MCF7 by methyl thiazolyl tetrazolium (MTT) method in vitro. Structure-activity relationships studies confirmed that N2-quaternarized compounds (4a, 4b, 8a and 8b) had more remarkable cytotoxic activities in vitro than harmine.


Guo L.,Xinjiang Huashidan Pharmaceutical Research Co. | Fan W.,Xinjiang Huashidan Pharmaceutical Research Co. | Chen X.,Xinjiang Huashidan Pharmaceutical Research Co. | Ma Q.,Xinjiang Huashidan Pharmaceutical Research Co. | And 2 more authors.
Chinese Journal of Organic Chemistry | Year: 2013

In search of more effective antitumor agents, based on the previous results of computer aided drug design. The starting material L-tryptophan reacted with formaldehyde via Pictet-Spengler condensation and followed by oxidation and decarboxylation to afford the intermediate β-carboline. The intermediate was further reacted with halogenated hydrocarbon by N9-alkylation and N2-quaternarization to obtain new β-carboline derivatives. Fourteen novel β-carboline derivatives were synthesized and characterized by 1H NMR, IR, MS and elemental analysis. Compound 5h was further studied by X-ray single crystal diffraction analysis. The antitumor activity of the target compounds was studied by MTT method. The results demonstrated that N2-quaternarized compounds (5a~5n) had more remarkable cytotoxic activities in vitro than 9-phenylpropyl-β-carboline (4). The tumor inhibition rates of the selected compounds 5e and 5h in mice bearing Lewis lung cancer. The compound 9 showed inhibition activity on transplanting-tumor growth of Lewis lung cancer. © 2013 Chinese Chemical Society & SIOC, CAS.


Ma Q.,Xinjiang Medical University | Ma Q.,Xinjiang Huashidan Pharmaceutical Research Co. | Guo L.,Xinjiang Huashidan Pharmaceutical Research Co. | Sun J.,Xinjiang Huashidan Pharmaceutical Research Co. | Fan W.-X.,Xinjiang Huashidan Pharmaceutical Research Co.
Yaoxue Xuebao | Year: 2013

The starting material L-tryptophan reacted with 4-chlorobenzaldehyde via Pictet-Spengler condensation and followed by oxidation and decarboxylation to afford the 1-(4-chlorophenyl)-β-carboline. The intermediate was further reacted with alkyl halogenide by N9-alkylation and N 2-quaternarization to obtain 12 novel 1-(4-chlorophenyl)-β- carboline derivatives. The chemical structures of all target compounds were characterized by elemental analyses, MS and 1H NMR spectra. The antitumor activities of the target compounds were evaluated by MTT method. The results demonstrated that N2-quaternarized compounds enhanced the antitumor activity significantly. In particular, compound 15 was found to be the most potent compound with IC50 values lower than 5 μmol·L-1 against 6 human tumor cells. These results confirmed that the N2-alkyl or aralkyl substituent on the β-carboline ring played an important role in the modulation of the antitumor activities.

Discover hidden collaborations