Cyclic amide derivatives as potential prodrugs II: N-hydroxymethylsuccinimide- / isatin esters of some NSAIDs as prodrugs with an improved therapeutic index

1999 ◽  
Vol 34 (7-8) ◽  
pp. 551-562 ◽  
Author(s):  
Nadia M Mahfouz ◽  
Farghaly A Omar ◽  
Tarek Aboul-Fadl
Keyword(s):  
Therapeutic Index ◽  
Amide Derivatives ◽  
Cyclic Amide

scholarly journals Synthesis of a novel amide derivative of valproic acid and 1,3,4-thiadiazole with antiepileptic activity

2020 ◽  
pp. 75-80 ◽  
Author(s):  
A.S. Malygin ◽  
M.A. Demidova ◽  
S.Ya. Skachilova ◽  
E.V. Shilova
Keyword(s):  
Valproic Acid ◽  
High Performance ◽  
Therapeutic Index ◽  
Probit Analysis ◽  
Great Promise ◽  
Antiepileptic Activity ◽  
Amide Derivative ◽  
Amide Derivatives ◽  
Derivatives Of ◽  
Acid Structure

Valproates are commonly used to treat various forms of epilepsy. Problems accompanying their clinical application include drug resistance, adverse effects, acute and chronic toxicity. Safer anticonvulsants with improved efficacy can be obtained through the chemical modification of valproic acid structure. Thiadiazole-linked amide derivatives of valproates hold great promise because 1,3,4-thiadiazole can improve the drug’s bioavailability and reduce its toxicity. The aim of this work was to synthesize a novel amide derivative of valproic acid and 1,3,4-thiadiazole exerting antiepileptic activity. The chemical structure of the synthesized valproate was studied by IR, proton NMR and 13С-NMR-spectroscopy, mass spectroscopy and elemental analysis. The purity and individuality of the compound was confirmed by thin-layer and high-performance liquid chromatography. Its antiepileptic activity was assessed in the test with intraperitoneally injected 250 mg/kg isoniazid and subsequent Probit analysis. The synthesized N-(5-ethyl-1,3,4-thiadiazol-2-yl)-2-propyl pentane amide (valprazolamide) had the following characteristics. ESI+MS: m/z 256.1 [M + H]+; MRM transitions: m/z 256.1 — m/z 81.0 and m/z 130.1. The valproate exerted antiepileptic activity against isoniazid-induced seizures in mice. In the test with isoniazid, ED50 of intraperitoneally injected VPZ was 126.8 mg/kg (95% CI: 65.5–245.4). Its therapeutic index was 7.3.

Discovery of novel 7-membered cyclic amide derivatives that inhibit 11beta-hydroxysteroid dehydrogenase type 1

2013 ◽  
Vol 23 (6) ◽  
pp. 1617-1621 ◽  
Author(s):  
Shuji Udagawa ◽  
Satoshi Sakami ◽  
Takahiro Takemura ◽  
Mikiya Sato ◽  
Takahiro Arai ◽  
...  
Keyword(s):  
Hydroxysteroid Dehydrogenase ◽  
Amide Derivatives ◽  
Cyclic Amide

Thrombolytic Treatment with Tissue-type Plasminogen Activator (t-PA) Containing Liposomes in Rabbits: a Comparison with Free t-PA

1995 ◽  
Vol 73 (03) ◽  
pp. 488-494 ◽  
Author(s):  
J L M Heeremans ◽  
R Prevost ◽  
M E A Bekkers ◽  
P Los ◽  
J J Emeis ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Therapeutic Index ◽  
Tissue Type ◽  
Jugular Vein Thrombosis ◽  
Thrombolytic Activity ◽  
Tissue Type Plasminogen Activator ◽  
Liposome Encapsulation ◽  
Thrombosis Model ◽  
Lysis Activity ◽  
Type Plasminogen Activator

SummaryIn this study, we aimed at improving the therapeutic index of tissue- type Plasminogen Activator (t-PA) as thrombolytic agent in the treatment of myocardial infarction. Liposome-encapsulated t-PA was tested in a rabbit jugular vein thrombosis model: administration of free t-PA (t-PA) as a bolus injection in the ear vein was compared to a similar administration of liposomal t-PA (t-PA-lip), liposomal t-PA in plasminogen-coated liposomes (Plg-t-PA-lip), a mixture of free t-PA and empty liposomes (t-PA+empty lip) and a saline-blank (blank) in terms of thrombolytic activity and side effects.Liposomal t-PA (t-PA-lip/Plg-t-PA-lip) showed a significantly better thrombolysis efficiency than equimolar doses of free t-PA (t-PA/ t-PA+ empty lip): about 0.24 mg/kg of liposomal t-PA practically equalled the lysis-activity of a dose of free t-PA of 1.0 mg/kg (t-PAlmg/kg). On the other hand, liposome encapsulation did not affect the systemic activation of alpha2-antiplasmin and plasminogen by t-PA.We conclude that for this model an improvement in thrombolytic efficacy of t-PA is achieved by liposome encapsulation of t-PA. As t-PA-lip and Plg-t-PA-lip -treatment induced similar results, targeting of liposomal t-PA by coupled glu-Plg remains a topic to be optimized in future studies.

Artemisinin (ART) Drug Delivery Using Mixed Non-ionic Surfactants and Evaluation of Their Efficiency in Different Cancer Cell Lines

2017 ◽  
Vol 4 (4) ◽  
Author(s):  
Elnaz Asgharkhani ◽  
Aazam Najmafshar ◽  
Mohsen Chiani
Keyword(s):  
Zeta Potential ◽  
Cell Line ◽  
Mtt Assay ◽  
Therapeutic Index ◽  
Stability Study ◽  
Polydispersity Index ◽  
Ionic Surfactants ◽  
Cytotoxicity Test ◽  
Molar Ratios ◽  
Chemotherapy Agent

This study aims to investigate the effects of different non-ionic surfactants on physicochemical properties of ART niosomes. ART is a natural compound that is used as an antimalarial and chemotherapy agent in medicine. ART has low bioavailability, stability and solubility. In order to solve these problems and enhancing the efficiency of the drug, nanotechnology was used. In the present study, several niosomal formulations of ART prepared using different molar ratios of Span 60 : Tween 60 : PEG-600: ART in PBS. These three formulations were FI (1:1:0.5:0.5), FII (2:1:0.5:0.5) and FIII (1:2:0.5:0.5), respectively. The encapsulation efficiency was measured by HPLC and the drug release was evaluated by dialysis method. The cytotoxicity test was determined by MTT assay. The size, zeta potential and polydispersity index of the vesicles was measured by Zeta Sizer. Stability study was performed within two months. The MTT assay results showed that cytotoxicity effect of these formulations on MCF-7 cell line is better than C6 cell line and the FIII had the best results for both of them. The entrapment efficiencies of the formulations I, II and III were obtained 82.2±1.88%, 75.5±0.92% and 95.5±1.23%, respectively. The results of size, zeta potential and polydispersity index indicated that the size of the vesicles is below 200 nm, their surface charge is about -35 mV and they were monodisperse. Stability and release study indicated that the formulation III has the best stability and release pattern. Therefore, the use of PEGylated niosomal ART can effectively improve its therapeutic index, stability and solubility.

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