90815-03-5Relevant academic research and scientific papers
Identification of low micromolar dual inhibitors for aldose reductase (ALR2) and poly (ADP-ribose) polymerase (PARP-1) using structure based design approach
Chadha, Navriti,Silakari, Om
supporting information, p. 2324 - 2330 (2017/05/09)
Clinical studies have revealed that diabetic retinopathy is a multifactorial disorder. Moreover, studies also suggest that ALR2 and PARP-1 co-occur in retinal cells, making them appropriate targets for the treatment of diabetic retinopathy. To find the dual inhibitors of ALR2 and PARP-1, the structure based design was carried out in parallel for both the target proteins. A series of novel thiazolidine-2,4-dione (TZD) derivatives were therefore rationally designed, synthesized and their in vitro inhibitory activities against ALR2 and PARP-1 were evaluated. The experimental results showed that compounds 5b and 5f, with 2-chloro and 4-fluoro substitutions, showed biochemical activities in micromolar and submicromolar range (IC50 1.34–5.03?μM) against both the targeted enzymes. The structure-activity relationship elucidated for these novel inhibitors against both the enzymes provide new insight into the binding mode of the inhibitors to the active sites of enzymes. The positive results of the biochemical assay suggest that these compounds may be further optimized and utilized for the treatment of diabetic retinopathy.
Design, synthesis and anticancer activity of 4-morpholinothieno[3,2-d]- pyrimidine derivatives bearing arylmethylene hydrazine moiety
Zhu, Wufu,Zhai, Xin,Fu, Qiangqiang,Guo, Fei,Bai, Mei,Wang, Jianqiang,Wang, Haiyan,Gong, Ping
experimental part, p. 1037 - 1045 (2012/10/08)
Three series of 4-morpholinothieno[3,2-d]pyrimidine derivatives containing arylmethylene hydrazine moiety (11a-f, 13a-k and 15a-h) were synthesized and their chemical structures as well as the relative stereochemistry were confirmed. The synthesized compounds were evaluated for their cytotoxicity against three cancer cell lines (H460, HT-29, MDA-MB-231). Most of them exhibited moderate to significant cytotoxicity and high-selectivity against one or more cell lines, especially compounds 11c, 13b, 15f and 15g possessing dramatically increased cytotoxicity as compared with the positive controls, which were further evaluated for six other cancer cell lines and one normal cell line. The most promising compound 11c, bearing 3,4-methylenedioxy phenyl group, showed remarkable cytotoxicity against H460, HT-29 and MDA-MB-231 cell lines with IC50 values of 0.003 μM, 0.42 μM and 0.74 μM, which was 1.6- to 290-fold more potent than GDC-0941.
Design, synthesis and 3D-QSAR analysis of novel 2-hydrazinyl-4- morpholinothieno[3,2-d]pyrimidine derivatives as potential antitumor agents
Zhu, Wufu,Liu, Yajing,Zhai, Xin,Wang, Xiao,Zhu, Yan,Wu, Di,Zhou, Hongyu,Gong, Ping,Zhao, Yanfang
, p. 162 - 175 (2013/01/15)
A series of 2-hydrazinyl-4-morpholinothieno[3,2-d]pyrimidine derivatives were synthesized and evaluated for their cytotoxic activities against five cancer cell lines. Most of them exhibited moderate to significant cytotoxic activities and high-selectivity against one or more cell lines, and nearly all of them had higher potency than positive controls against MDA-MB-231 cell line. The most promising compound 15f showed strong cytotoxic activities against H460, HT-29 and MDA-MB-231 cell lines, which were 1.7- to 66.5-folds more active than 2-(1H-Indazol-4-yl)-6-((4-(methylsulfonyl)-1-piperazinyl)methyl)-4-(4- morpholinyl)thieno[3,2-d]pyrimidine(GDC-0941). To investigate the SARs of thieno[3,2-d]pyrimidine derivatives in more details, CoMFA (q2 = 0.436, r2 = 0.937) and CoMSIA (q2 = 0.706, r2 = 0.947) models on H460 cell line were established. The generated 3D-QSAR models can be used for further rational design of novel thienopyrimidines as highly potent and selective cytotoxic agents.
Synthesis and biological evaluation of novel 6-hydrazinyl-2,4-bismorpholino pyrimidine and 1,3,5-triazine derivatives as potential antitumor agents
Zhu, Wufu,Liu, Yajing,Zhao, Yanfang,Wang, Haiyan,Tan, Li,Fan, Weijie,Gong, Ping
, p. 812 - 821,10 (2020/09/09)
A series of 6-hydrazinyl-2,4-bismorpholino pyrimidine and 1,3,5-triazine derivatives (5a-5l and 8a-8o) were synthesized and their chemical structures as well as the relative stereochemistry were confirmed. All the synthesized compounds were evaluated for antiproliferative activity against three cancer cell lines (H460, HT-29, and MDA-MB-231). Several potent compounds were further evaluated against two other cell lines (U87MG, H1975). Most of the prepared compounds, particularly compounds 5c and 5j with IC50 values (0.07 and 0.05 μM, respectively) in the nM range, exhibited moderate to excellent antiproliferative activity and high selectivity against the H460 cancer cell line as compared with compound 1. The most promising compound 5j, possessing a cyano group at the 3-position of the benzene ring, showed strong antiproliferative activity against H460, HT-29, and MDA-MB-231 cell lines with IC50 values of 0.05, 6.31, and 6.50 μM, which were 4.6- to 190.4-fold more active than compound 1 (9.52, 29.24, and 36.21 μM), respectively. Copyright
Analogues and derivatives of oncrasin-1, a novel inhibitor of the C-terminal domain of RNA polymerase II and their antitumor activities
Wu, Shuhong,Wang, Li,Guo, Wei,Liu, Xiaoying,Liu, Jinsong,Wei, Xiaoli,Fang, Bingliang
experimental part, p. 2668 - 2679 (2011/06/27)
To optimize the antitumor activity of oncrasin-1, a small molecule RNA polymerase II inhibitor, we evaluated 69 oncrasin-1 analogues for their cytotoxic activity against normal human epithelial cells and K-Ras mutant tumor cells. About 40 of those compoun
Synthesis and antifungal activity of new 1-halogenobenzyl-3-imidazolylmethylindole derivatives
Na, Young-Min,Le Borgne, Marc,Pagniez, Fabrice,Le Baut, Guillaume,Le Pape, Patrice
, p. 75 - 87 (2007/10/03)
A series of 1-benzyl-3-(imidazol-1-ylmethyl)indole derivatives 35-46 were prepared under mild reaction conditions and tested for their antifungal activity. Pharmacomodulation at N1, C2 and C5 of the indole ring and at the level of the alkyl chain (R1) was carried out starting from the corresponding 3-acylindoles 6, 7 or 3-formylindoles 11-22. Target imidazolyl compounds 35-46 were obtained in satisfactory yields by CO2 elimination from the intermediate carbamates. All of the compounds were evaluated in vitro against two human fungal pathogens, Candida albicans (CA980001) and Aspergillus fumigatus (AF980003); amphotericin B, fluconazole and itraconazole were used as references. Seven out of 27 compounds (35b, 35e, 35g, 35h, 36a, 38a and especially 40a) exerted significant antifungal activity against C. albicans, with MIC in the range of 1-6 μg mL-1. As regards inhibitory activity against A. fumigatus, the MIC figures of most of our compounds were in excess of 20 μg mL-1 in contrast to the reference drugs, amphotericin B and itraconazole, whose MIC90 and MIC80 values were 0.14 and 0.50 μg mL-1, respectively. The most potent compound, 45a, exhibited MIC value (8±1 μg mL-1) 16-fold higher than that of itraconazole.
Synthesis and antimycobacterial activity of some indole derivatives of pyridine-2-carboxamidrazone and quinoline-2-carboxamidrazone
Mamolo,Vio,Banfi
, p. 65 - 70 (2007/10/03)
A series of pyridine-2-carboxamidrazone and quinoline-2-carboxamidrazone derivatives containing the indole moiety was prepared. Some of the synthesized compounds showed an interesting in vitro antimycobacterial activity against a strain of Mycobacterium tuberculosis.
Syntheses and in vitro antimycotic activities of 1-benzyl-3-(1-imidazolylmethyl)indoles
Cavrini,Gatti,Roveri,Cesaroni,Mazzoni,Fiorentini
, p. 662 - 668 (2007/10/02)
Syntheses of seventeen 1-benzyl-3-(1-imidazolylmethyl)indoles with substituents at the benzyl moiety and at the indole C-2 position are described. The compounds were tested for their antifungal activities in vitro determination of the minimum inhibitory concentration (MIC). Three compounds exhibited appreciable activities against Cr. neoformans.
