355815-83-7Relevant academic research and scientific papers
Searching for new agents active against Candida albicans biofilm: A series of indole derivatives, design, synthesis and biological evaluation
Pandolfi, Fabiana,D'Acierno, Federica,Bortolami, Martina,De Vita, Daniela,Gallo, Fabio,De Meo, Alessandra,Di Santo, Roberto,Costi, Roberta,Simonetti, Giovanna,Scipione, Luigi
, p. 93 - 106 (2019/01/23)
Candida albicans biofilm represents a major clinical problem due to its intrinsic tolerance to anti-fungal compounds and it has been highly related to infections in catheterized patients. Few compounds are described as able to inhibit biofilm formation or to interfere with preformed biofilm of C. albicans. Here we report the in vitro evaluation of anti-biofilm activity on C. albicans ATCC 10231 of a series of new and already known amine and amide indole derivatives. Among the studied compounds, fifteen resulted active on C. albicans ATCC 10231 biofilm, with BMIC50 ≤ 16 μg/mL. Three of them (7, 23 and 33) showed a selectivity towards mature biofilm and the most active of them was the compound 23 (BMIC50 = 4 μg/mL). On the other hands, two different compounds (21 and 22) were selective towards biofilm formation with BMIC50 values of 8 μg/mL. Otherwise, compounds 16 and 17 resulted active on biofilm formation, with BMIC50 of 8 μg/mL and 2 μg/mL respectively, and on mature biofilm with BMIC50 of 2 μg/mL. These two last compounds also showed an interesting activity towards the planktonic cells of C. albicans. A selection of the more active compounds was also evaluated on different C. albicans strains (PMC1042, PMC1083 and ATCC 10261), showing a comparable or higher anti-biofilm activity, especially on mature biofilm. In vivo toxicity studies using the Galleria mellonella larvae, were finally carried out on more active indole derivatives, showing that they are poorly toxic even at the highest concentrations tested (500–1000 μg/mL).
Structure-Based Design of Potent Nicotinamide Phosphoribosyltransferase Inhibitors with Promising in Vitro and in Vivo Antitumor Activities
Bai, Jinhong,Liao, Chenzhong,Liu, Yanghan,Qin, Xiaochu,Chen, Jiaxuan,Qiu, Yatao,Qin, Dongguang,Li, Zheng,Tu, Zheng-Chao,Jiang, Sheng
supporting information, p. 5766 - 5779 (2016/07/06)
Inhibition of nicotinamide phosphoribosyltransferase (NAMPT) has the potential to directly limit NAD production in cancer cells and is an effective strategy for cancer treatment. Using a structure-based strategy, we have designed a new class of potent small-molecule inhibitors of NAMPT. Several designed compounds showed promising antiproliferative activities in vitro. (E)-N-(5-((4-(((2-(1H-Indol-3-yl)ethyl)(isopropyl)amino)methyl)phenyl)amino)pentyl)-3-(pyridin-3-yl)acrylamide, 30, bearing an indole moiety, has an IC50 of 25.3 nM for binding to the NAMPT protein and demonstrated promising inhibitory activities in the nanomolar range against several cancer cell lines (MCF-7 GI50 = 0.13 nM; MDA-MB-231 GI50 = 0.15 nM). Triple-negative breast cancer is the most malignant subtype of breast cancer with no effective targeted treatments currently available. Significant antitumor efficacy of compound 30 was achieved (TGI was 73.8%) in an orthotopic MDA-MB-231 triple-negative breast cancer xenograft tumor model. This paper reports promising lead molecules for the inhibition of NAMPT which could serve as a basis for further investigation.
Synthesis of tetrahydro-β-carbolines via isomerization of N-allyltryptamines: A metal-catalyzed variation on the Pictet-Spengler theme
Ascic, Erhad,Hansen, Casper L.,Le Quement, Sebastian T.,Nielsen, Thomas E.
supporting information; experimental part, p. 3345 - 3347 (2012/05/04)
An efficient and broadly applicable alternative to the classical Pictet-Spengler synthesis of tetrahydro-β-carbolines is presented. The method relies on metal-catalyzed isomerization of allylic amines to form reactive iminium intermediates which can be trapped by a tethered indole nucleophile. The Royal Society of Chemistry 2012.
Highly enantioselective pictet-spengler reaction catalyzed by SPINOL-phosphoric acids
Huang, Dan,Xu, Fangxi,Lin, Xufeng,Wang, Yanguang
supporting information; experimental part, p. 3148 - 3152 (2012/04/17)
Chiral SPINOL-phosphoric acids are highly enantioselective catalysts for the asymmetric Pictet-Spengler reaction of Nb-α-naphthylmethyl tryptamines with a series of aliphatic and aromatic aldehydes, affording optically active tetrahydro-β-carbolines in excellent yields and ee values. The current protocol has been applied in the asymmetric total synthesis of (-)-harmicine. Copyright
