501912-85-2Relevant academic research and scientific papers
Ring-opened tetrahydro-γ-carbolines display cytotoxicity and selectivity with histone deacetylase isoforms
Nepali, Kunal,Lee, Hsueh-Yun,Lai, Mei-Jung,Ojha, Ritu,Wu, Tung-Yun,Wu, Gu-Xian,Chen, Mei-Chuan,Liou, Jing-Ping
, p. 115 - 127 (2016/12/30)
This study is focused on modification of the indole moiety and the N1-zinc binding domain of tubastatin A, and the effects of such changes on biological activity. Fourteen N-substituted indoles (5–18) were synthesized and structure-activity relationship studies indicated that the change of the tetrahydro-γ-carboline in tubastatin A led to substituted indoles (compounds 7, 11, and 15) which showed significant improvements of selective inhibition for HDAC6 over HDAC1 and HDAC2 in comparison to ACY1215, a compound undergoing clinical trials. In addition, attachment of different hydroxamic acid groups, the zinc binding motif at the N1 position, contributes to the antiproliferative activity in cancer cells. Several synthetic compounds exhibited potent growth inhibition in a broad spectrum of tumor cell lines, induced irreversible growth arrest capacities by suppressing colony formation ability and activated the apoptosis pathway. The data provide compelling evidence that our newly synthesized compounds with type B to D hydroxamic acid groups as the zinc binding motif at the N1 position are potent selective inhibitors of HDAC6 and could be investigated preclinically as potential anticancer drugs.
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.
