Antileishmanial activity and insights into the mechanisms of action of symmetric Au(I) benzyl and aryl-N-heterocyclic carbenes

Author(s):  
Letícia B. Rosa ◽  
Carolina Galuppo ◽  
Rochanna L.A. Lima ◽  
Josielle V. Fontes ◽  
Fábio S. Siqueira ◽  
...  
2018 ◽  
Vol 143 ◽  
pp. 1635-1643 ◽  
Author(s):  
Chen Zhang ◽  
Sandra Bourgeade Delmas ◽  
Álvaro Fernández Álvarez ◽  
Alexis Valentin ◽  
Catherine Hemmert ◽  
...  

2021 ◽  
pp. 109690
Author(s):  
Bruna Taciane da Silva Bortoleti ◽  
Manoela Daiele Gonçalves ◽  
Fernanda Tomiotto-Pellissier ◽  
Priscila Goes Camargo ◽  
João Paulo Assolini ◽  
...  

Author(s):  
Esteban Vargas ◽  
Fernando Echeverri ◽  
Yulieth A. Upegui ◽  
Sara M. Robledo ◽  
Wiston Quiñones

Cutaneous leishmaniasis (CL) is a neglected tropical disease, which causes severe skin lesions. Due to the lack of effective vaccines, and toxicity or reduced effectiveness of available drugs in addition to complex and prolonged treatments, there is an urgent need to develop alternatives for the treatment for CL with different mechanisms of action. In our effort to search for new promising hits against Leishmania parasites we prepared 18 acyl hydrazone derivatives of thiochroman-4-ones. Compounds were evaluated for their in vitro antileishmanial activity against the intracellular amastigote form of Leishmania panamensis and cytotoxic activity against human monocytes (U-937 ATCC CRL-1593.2). Our results show that derivatization of the thiochroman-4-ones with acyl hydrazones significantly enhances the antileishmanial activity. Among the compounds tested semicarbazone and thiosemicarbazone derivatives of thioflavanone 19 and 20 displayed the highest antileishmanial activities, with EC50 values of 5.4 and 5.1 µM and low cytotoxicities (100.2 and 50.1 µM respectively), resulting in higher indexes of selectivity (IS).


2003 ◽  
Vol 19 (3) ◽  
pp. 164-174 ◽  
Author(s):  
Stephen N. Haynes ◽  
Andrew E. Williams

Summary: We review the rationale for behavioral clinical case formulations and emphasize the role of the functional analysis in the design of individualized treatments. Standardized treatments may not be optimally effective for clients who have multiple behavior problems. These problems can affect each other in complex ways and each behavior problem can be influenced by multiple, interacting causal variables. The mechanisms of action of standardized treatments may not always address the most important causal variables for a client's behavior problems. The functional analysis integrates judgments about the client's behavior problems, important causal variables, and functional relations among variables. The functional analysis aids treatment decisions by helping the clinician estimate the relative magnitude of effect of each causal variable on the client's behavior problems, so that the most effective treatments can be selected. The parameters of, and issues associated with, a functional analysis and Functional Analytic Clinical Case Models (FACCM) are illustrated with a clinical case. The task of selecting the best treatment for a client is complicated because treatments differ in their level of specificity and have unequally weighted mechanisms of action. Further, a treatment's mechanism of action is often unknown.


Author(s):  
Joe L. Martinez ◽  
Patricia H. Janak ◽  
Susan B. Weinberger ◽  
Gery Schulteis

Planta Medica ◽  
2012 ◽  
Vol 78 (05) ◽  
Author(s):  
HMTB Hereath ◽  
BL Tekwani ◽  
NPD Nanayakkara

Planta Medica ◽  
2012 ◽  
Vol 78 (11) ◽  
Author(s):  
CBS Lau ◽  
VKM Lau ◽  
CL Liu ◽  
PKK Lai ◽  
JCW Tam ◽  
...  

Planta Medica ◽  
2016 ◽  
Vol 81 (S 01) ◽  
pp. S1-S381 ◽  
Author(s):  
B Ovalle-Magallanes ◽  
A Madariaga-Mazón ◽  
A Navarrete ◽  
R Mata

1979 ◽  
Author(s):  
L Miles ◽  
J Burnier ◽  
M Verlander ◽  
M Goodman ◽  
A Kleiss ◽  
...  

Flu-HPA is one of a series of flufenamic acid derivations that enhances plasminogen-dependent clot lysis in vitro. Studies of possible mechanisms of action of Flu-HPA were undertaken. The influence of Flu-HPA on the inhibition of purified plasmin by purified PI was studied. PI activity was assessed by its inhibition of the clevage of the tripeptide S-2251 (H-D-Val-Leu-Lys-pNA) by plasmin. Flu-HPA was dissolved in DMF or in methonol and preincubated with PI before addition of plasmin. At Flu-HPA concentrations greater than 1mM and up to 60mM, the inhibitory activity of PI was totally lost. The inhibitory effect of normal human plasma on plasmin was also completely abolished at concentrations of Flu-HPA between 2.5 and 40mM. The effect of Flu-HPA on the inhibition of purified plasma kallikrein by purified CI-Inh was also studied. CI-Inh activity was measured by its inhibition of cleavage of the tripeptide Bz-Pro-Phe-Arg-pNA by kallikrein. When Flu-HPA, dissolved in DMF or in methonol, was preincubated with CI-Inh, a concentration dependent inhibition of CI-Inh activity was observed. CI-Inh activity was abolished by concentrations of Flu-HPA greater than 1mM. Flu-HPA also inhibited the activity of CI-Inh on purified Factor XIIa. These observations suggest that this flufenamic acid derivative may enhance fibrinolysis not only by inhibiting PI activity but also by decreasing the inactivation of plasminogen activators by CI-Inh.


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