4219-52-7Relevant academic research and scientific papers
Design, synthesis and evaluation of 4-substituted anthra[2,1-c][1,2,5]thiadiazole-6,11-dione derivatives as novel non-camptothecin topoisomerase I inhibitors
Dong, Guoqiang,Fang, Yuxin,Liu, Yang,Liu, Na,Wu, Shanchao,Zhang, Wannian,Sheng, Chunquan
supporting information, p. 1929 - 1933 (2017/04/07)
Previously, 4-tosylanthra[1,2-c][1,2,5]thiadiazole-6,11-dione (1) was identified as a novel non-camptothecin topoisomerase I (Top1) inhibitor by structure-based virtual screening. Herein, a series of 4-substituted derivatives were designed and synthesized. Most of them showed potent Top1 inhibitory activity. Their in vitro antiproliferative activity was also evaluated in A549, HCT-116 and ZR-75-30 human cancer cell lines. Compound 8s showed good antiproliferative activity with IC50 of 0.52?μM and 0.42?μM against HCT-116 and ZR-75-30 cell line, respectively. Top1 unwinding assay and molecular modeling studies rationalized the mode of action of this new class of inhibitors.
4-substituted anthracene and [1,2-c] [1, 2, 5] thiadiazole -6,11-dione derivatives and its preparation method and application
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Paragraph 0148-0149, (2016/10/09)
The invention relates to the technical field of medicine. The invention provides a 4-substituted anthra[1,2-c][1,2,5]thiadiazole-6,11-dione derivative and its pharmaceutically acceptable salt. The structural general formula of the compound is as shown in
Novel anthra[1,2-c][1,2,5]thiadiazole-6,11-diones as promising anticancer lead compounds: Biological evaluation, characterization & molecular targets determination
Ali, Ahmed Atef Ahmed,Lee, Yu-Ru,Chen, Tsung-Chih,Chen, Chun-Liang,Lee, Chia-Chung,Shiau, Chia-Yang,Chiang, Chiao-Hsi,Huang, Hsu-Shan
, (2016/05/09)
The novel compounds NSC745885 and NSC757963 developed at our laboratory were tested against a panel of 60 cancer cell lines at the National Cancer Institute, USA, and a panel of 39 cancer cell lines at the Japanese Foundation of Cancer Research. Both compounds demonstrated selective unique multi-log differential patterns of activity, with GI50 values in the sub-micro molar range against cancer cells rather than normal cardiac cells. NSC757963 showed high selectivity towards the leukemia subpanel. Activities of both compounds strongly correlated to expression of NFKB1 and CSNK2B genes, implying that they may inhibit the NF-κB pathway. Immunocytochemical microscopy of OVCAR-3 cells showed clear cytosolic accumulation of the NF-κB p65 subunit following treatment. Western blotting showed dose dependent inhibition of the nuclear expression of the NF-κB p65 subunit with subsequent accumulation in the cytosol following treatment. Docking experiments showed binding of both compounds to the NF-κB activator IKKβ subunit preventing its translocation to the nucleus. Collectively, these results confirm the ability of our compounds to inhibit the constitutively active NF-κB pathway of OVCAR-3 cells. Furthermore, COMPARE analysis indicated that the activity of NSC757963 is similar to the antituberculosis agent rifamycin SV, this was confirmed by testing the antimycobacterial activity of NSC757963 against Mycobacterium tuberculosis, results revealed potent activity suitable for use in clinical practice. Molecular properties and Lipinski's parameters predicted acceptable bioavailability properties with no indication of mutagenicity, tumorigenicity, irritability and reproductive effects. Oral absorption experiments using the human Caco-2 model showed high intestinal absorption of NSC745885 by passive transport mechanism with no intestinal efflux or active transport mechanisms. The unique molecular characterization as well as the illustrated anticancer spectra of activity and bioavailability properties warrant further development of our compounds and present a foundation brick in the pre-clinical investigations to implement such compounds in clinical practice.
Ring fusion strategy for synthesis and lead optimization of sulfur-substituted anthra[1,2-c[[1,2,5]thiadiazole-6,11-dione derivatives as promising scaffold of antitumor agents
Lee, Yu-Ru,Chen, Tsung-Chih,Lee, Chia-Chung,Chen, Chun-Liang,Ahmed Ali, Ahmed Atef,Tikhomirov, Alexander,Guh, Jih-Hwa,Yu, Dah-Shyong,Huang, Hsu-Shan
, p. 661 - 676 (2015/09/21)
A series of sulfur-substituted anthra[1,2-c][1,2,5]thiadiazole-6,11-diones were synthesized and evaluated using the cell proliferations, apoptosis and NCI-60 cell panel assays. Also, the signaling pathways that account for their activities were investigated. Compounds 2, 3, 4a, 4d, 4f, 4i, 4k, 5b, 5c, 5d, 5f, 5g, 6b, 6c, 6d, 6e, 6g, 7a and 7g were selected by NCI. Among the tested compounds, 6g appeared to be the most active compound of this series that not only induced apoptosis in DU-145 cancer cells but also attenuated the ERK1/2 and p38 signaling pathways. All test compounds exhibited diverse cytostatic and cytotoxic activities that warrant further development as potential anticancer agents.
HETEROANNELATED ANTHRAQUINONE DERIVATIVES AND THE SYNTHESIS METHOD THEREOF
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Page/Page column 10, (2009/10/17)
A heteroannelated anthraquinone derivative compound is provided. The heteroannelated anthraquinone derivative compound is represented by a formula (I): wherein R1 is a substituent being one selected from a group consisting of i) a first substituent being one selected from a group consisting of a hydryl group, an amino group, a nitro group, a hydroxyl group and a cyan group, ii) a second substituent being one selected from a group consisting of (CH2)nX, a straight (CH2)n alkyl group, a (CH2)n alkoxyl group, a branched (CH2)n alkyl group, a C3?C12nephthenic group, and a C3?C12 cyclic alkoxyl group, wherein 1=n=12, and X is a halogen, iii) a third substituent being one selected from a group consisting of a straight C1?C8 alkyl group with a double-bond, a C1?C8 alkoxyl group with a double-bond, a branched C1?C8 alkyl group with a double-bond and a C3?C8 nephthenic group with a double-bond, and iv) a fourth substituent of a C5?C12 heterocyclic group.
Synthesis, cytotoxicity and human telomerase inhibition activities of a series of 1,2-heteroannelated anthraquinones and anthra[ 1,2-d]imidazole-6,11 -dione homologues
Huang, Hsu-Shan,Chen, Tsung-Chih,Chen, Ruei-Huei,Huang, Kuo-Feng,Huang, Fong-Chun,Jhan, Jing-Ru,Chen, Chun-Liang,Lee, Chia-Chung,Lo, Yang,Lin, Jing-Jer
experimental part, p. 7418 - 7428 (2011/02/24)
A series of 1,2-heteroannelated anthraquinones and anthra[1,2-d]imidazole- 6,11-dione tetracyclic analogues with different side chain were prepared using an various synthetic route via acylation, cyclization, condensation, and intramolecular heterocyclization. Tetracyclic system containing alkyl and aryl, aromatic and heterocyclic, linear and cyclic, polar and apolar, and basic and acids residues were incorporated. They were evaluated for their effects on telomerase activity, hTERT expression, cell proliferations, and in vitro cytotoxicity against NCI's 60 cell line human tumor screen. Compounds 4, 11, 12, 14, 15, 16, 17, 19, 20, 23, 25, and 26 were selected by the NCI for one dose screening program and further studies on 4, 23 and 25 where the curves cross these lines represent the interpolated values to cause 50% growth inhibition (GI50), total growth inhibition (TGI) and 50% cell killing (LC 50). respectively. Further studies did not reveal any compound that showed potent and significant on telomerase inhibitory activity and hTERT repressing ability. Comparative testing of these compounds in the NCI's screen revealed varying levels of potency and differential cytotoxicity, apparently related to the unsaturation levels in and substitution patterns on the core ring system. It appeared that addition of a fourth planar aromatic system to a tricyclic chromophore might enhances potent cytotoxic agents, at a level equivalent to a second side chain in one of the tricyclic series. Although the exact mechanism of how this pharmacophore contributes to its activity is still unclear, however, the group in the extended arm of the tetracyclic system might contribute to proper binding to the residues within the grove of G-quadruplex structure.
