943451-01-2Relevant academic research and scientific papers
Synthesis of a sugar-based thiosemicarbazone series and structure-activity relationship versus the parasite cysteine proteases rhodesain, cruzain, and Schistosoma mansoni cathepsin B1
Fonseca, Nayara Cristina,Da Cruz, Luana Faria,Da Silva Villela, Filipe,Do Nascimento Pereira, Glaécia Aparecida,De Siqueira-Neto, Jair Lage,Kellar, Danielle,Suzuki, Brian M.,Ray, Debalina,De Souza, Thiago Belarmino,Alves, Ricardo José,Júnior, Policarpo Ademar Sales,Romanha, Alvaro José,Murta, Silvane Maria Fonseca,McKerrow, James H.,Caffrey, Conor R.,De Oliveira, Renata Barbosa,Ferreira, Rafaela Salgado
, p. 2666 - 2677 (2015)
The pressing need for better drugs against Chagas disease, African sleeping sickness, and schistosomiasis motivates the search for inhibitors of cruzain, rhodesain, and Schistosoma mansoni CB1 (SmCB1), the major cysteine proteases from Trypanosoma cruzi, Trypanosoma brucei, and S. mansoni, respectively. Thiosemicarbazones and heterocyclic analogues have been shown to be both antitrypanocidal and inhibitory against parasite cysteine proteases. A series of compounds was synthesized and evaluated against cruzain, rhodesain, and SmCB1 through biochemical assays to determine their potency and structure-activity relationships (SAR). This approach led to the discovery of 6 rhodesain, 4 cruzain, and 5 SmCB1 inhibitors with 50% inhibitory concentrations (IC50s) of ≤10 μM. Among the compounds tested, the thiosemicarbazone derivative of peracetylated galactoside (compound 4i) was discovered to be a potent rhodesain inhibitor (IC50 = 1.2 ± 1.0 μM). The impact of a range of modifications was determined; removal of thiosemicarbazone or its replacement by semicarbazone resulted in virtually inactive compounds, and modifications in the sugar also diminished potency. Compounds were also evaluated in vitro against the parasites T. cruzi, T. brucei, and S. mansoni, revealing active compounds among this series.
Synthesis and antimicrobial activity of glycosylated 2-Aryl?5?amidinobenzimidazoles
de Souza, Thiago B.,Oliver, Josidel C.,Gomes, Ana Paula B.,Arag?o, Cícero Flávio S.,Ferreira, Leandro S.,Nogueira, Fernando Henrique A.,Dias, Amanda Latércia T.,Alves, Ricardo J.
, p. 1304 - 1317 (2018/05/07)
A series of new glycosylated 2-aryl-5-amidinobenzimidazoles derived from four different carbohydrates (D-glucose, D-galactose, N-acetyl-D-glucosamine and lactose) were synthesized by the condensation of the appropriate 4-formyl-3-methoxyphenyl glycoside with 4-amidino- or 4-N-isopropylamidino-ortho-phenylenediamine hydrochloride. All the compounds were properly characterized by high resolution mass spectrometry, uni- and bidimensional1H and13C nuclear magnetic resonance and then were evaluated for their antibacterial and antifungal potential. Considering the antifungal potential of them, two derivatives were active against Candida parapsilosis at 96.4 μmol L-1 and another was active against this same strain at 83.5 μmol L-1. In addition, one benzamidine showed activity against Candida glabrata at 97 μmol L-1. Considering the antibacterial potential of these compounds, six of them showed better activity against three different stains: three of them with IC50 of 96.4, 97 and 83.5 μmol L-1 against Gram-positive Micrococcus luteus, the other two with IC50 96.5 and 96.4 μmol L-1 against Gram-positive Enterococcus faecalis and one against Gram-negative Escherichia coli at 90.5 μmol L-1. These findings suggest this structural pattern can be employed for design of more potent agents for discovery of new antimicrobial drug candidates.
Synthesis of Glycosylated Chrysin Derivatives Via Ester Linkers
Fei, Gaishun,Fan, Xiaofei,Ma, Huiping,Fan, Pengchang,Jia, Zhengping,Jing, Linlin
, p. 602 - 610 (2016/08/31)
A series of glycosylated chrysin derivatives have been synthesized in good yields with simple procedures and mild reaction conditions. Six different kinds of sugar moieties were introduced through each ester linker.
Synthesis and biological evaluation of glycosylated psoralen derivatives
Chen, Chao-Yue,Sun, Jian-Guo,Liu, Fei-Yan,Fung, Kwok-Pui,Wu, Ping,Huang, Zhi-Zhen
experimental part, p. 2598 - 2606 (2012/05/20)
A novel route for the efficient synthesis of a target psoralen moiety, 4,4′-dimethylxanthotoxol, has been developed, which need only four steps using cheap pyrogallol as a starting material. Subsequently, a range of new glycosylated psoralen derivatives w
Study on glycosylated prodrugs of toxoflavins for antibody-directed enzyme tumor therapy
Wang, Shusheng,Liu, Dan,Zhang, Xu,Li, Shengyu,Sun, Yongxu,Li, Jia,Zhou, Yifa,Zhang, Liping
, p. 1254 - 1260 (2008/02/02)
Eight novel toxoflavin glycosides, which are potential prodrugs in antibody directed enzyme prodrug therapy (ADEPT), were synthesized. The structures of all toxoflavin glycosides were characterized by 13C NMR spectroscopy, elemental analysis, and MS. Their enzymatic hydrolysis activities were tested against β-glucosidase (EC.3.2.1.21).
