Synthesis and Structure—Activity Relationships of Novel IKK-β Inhibitors. Part 2. Improvement of in vitro Activity.

ChemInform ◽  
2004 ◽  
Vol 35 (49) ◽  
Author(s):  
Toshiki Murata ◽  
et al. et al.
Keyword(s):  
Vitro Activity ◽  
In Vitro Activity ◽  
Structure Activity Relationships ◽  
Structure Activity

scholarly journals Novel Azolylalkyloxy Compounds with Antipicornaviral Activity

1995 ◽  
Vol 6 (4) ◽  
pp. 245-254 ◽  
Author(s):  
M. D. Abel ◽  
A. D. Cameron ◽  
C. M. Ha ◽  
C. A. Koski ◽  
H. T. Luu ◽  
...  
Keyword(s):  
Vitro Activity ◽  
In Vitro Activity ◽  
Optimal Length ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Wide Range ◽  
Highly Effective ◽  
Qualitative Structure

A novel series of azolylalkyloxy compounds was designed, synthesized and evaluated for antipicornaviral activity. Several of the compounds exhibited in vitro activity comparable to that of Disoxarll. An investigation of qualitative structure-activity relationships indicated that the optimal length of the alkyI chain is six or seven carbon atoms, with seven being marginally superior. The effect of different azole moieties on activity was relatively small, with 3-methylisoxazole and 4-methylthiazole being most effective. The nature of the oxy substituent was found to be extremely important for antipicornaviral activity. The 2-dibenzofuryl group proved to be the most effective oxy substituent for this class of compounds. Compounds 11 and 22, combining dibenzofuran with 3-methylisoxazole and 4-methylthiazole, respectively, were highly effective in vitro against a wide range of human rhinoviruses as well as several enteroviruses.

scholarly journals Anti-Toxoplasma gondii Activities and Structure-Activity Relationships of Novel Fluoroquinolones Related to Trovafloxacin

1999 ◽  
Vol 43 (7) ◽  
pp. 1783-1787 ◽  
Author(s):  
Anis A. Khan ◽  
Fausto G. Araujo ◽  
Katherine E. Brighty ◽  
Thomas D. Gootz ◽  
Jack S. Remington
Keyword(s):  
Toxoplasma Gondii ◽  
Inhibitory Concentration ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Increased Activity

ABSTRACT Eleven novel fluoroquinolones closely related to trovafloxacin were evaluated for their in vitro activity against Toxoplasma gondii, and their structure-activity relationships were examined. The 50% inhibitory concentration (IC50) of trovafloxacin against T. gondii was 2.93 μM; the IC50 of the 11 analogs ranged from 0.53 to 14.09 μM. Six analogs had IC50s lower than that of trovafloxacin. Examination of the structure-activity relationships of the compounds revealed that addition of a -CH3 at C-5 of the 1,8-naphthyridone ring, at C-2 of the azabicyclohexane ring, or on the -NH2 at the 6 position of the azabicyclohexane ring resulted in a four- to sixfold increase in activity. Moreover, replacement of 2,4-difluorophenyl by cyclopropyl at N-1 of the 1,8-naphthyridone ring increased activity twofold, and moving the -NH2 one atom further away from the azabicyclohexane ring decreased activity. There was no difference between the naphthyridone and quinolone analogs. These results indicate that structure-activity studies of compounds related to drugs active against T. gondii may be useful in producing compounds with more potent activities against the parasite.

Synthesis and structure–activity relationships of novel IKK-β inhibitors. Part 2: Improvement of in vitro activity

2004 ◽  
Vol 14 (15) ◽  
pp. 4013-4017 ◽  
Author(s):  
Toshiki Murata ◽  
Mitsuyuki Shimada ◽  
Hiroshi Kadono ◽  
Sachiko Sakakibara ◽  
Takashi Yoshino ◽  
...  
Keyword(s):  
Vitro Activity ◽  
In Vitro Activity ◽  
Structure Activity Relationships ◽  
Structure Activity

scholarly journals Anti-Toxoplasma Activities of 24 Quinolones and Fluoroquinolones In Vitro: Prediction of Activity by Molecular Topology and Virtual Computational Techniques

2000 ◽  
Vol 44 (10) ◽  
pp. 2771-2776 ◽  
Author(s):  
Rafael Gozalbes ◽  
Monique Brun-Pascaud ◽  
Ramon Garcia-Domenech ◽  
Jorge Galvez ◽  
Pierre-Marie Girard ◽  
...  
Keyword(s):  
Drug Target ◽  
Cross Validation ◽  
Quantitative Structure Activity Relationship ◽  
Vitro Activity ◽  
Computational Techniques ◽  
In Vitro Activity ◽  
Multilinear Regression ◽  
Linear Discriminant ◽  
Structure Activity

ABSTRACT The apicoplast, a plastid-like organelle of Toxoplasma gondii, is thought to be a unique drug target for quinolones. In this study, we assessed the in vitro activity of quinolones againstT. gondii and developed new quantitative structure-activity relationship models able to predict this activity. The anti-Toxoplasma activities of 24 quinolones were examined by means of linear discriminant analysis (LDA) using topological indices as structural descriptors. In parallel, in vitro 50% inhibitory concentrations (IC50s) were determined in tissue culture. A multilinear regression (MLR) analysis was then performed to establish a model capable of classifying quinolones by in vitro activity. LDA and MLR analysis were applied to virtual structures to identify the influence of each atom or substituent of the quinolone ring on anti-Toxoplasma activity. LDA predicted that 20 of the 24 quinolones would be active against T. gondii. This was confirmed in vitro for most of the quinolones. Trovafloxacin, grepafloxacin, gatifloxacin, and moxifloxacin were the quinolones most potent against T. gondii, with IC50s of 0.4, 2.4, 4.1, and 5.1 mg/liter, respectively. Using MLR analysis, a good correlation was found between measured and predicted IC50s (r 2 = 0.87, cross-validationr 2 = 0.74). MLR analysis showed that the carboxylic group at position C-3 of the quinolone ring was not essential for anti-Toxoplasma activity. In contrast, activity was totally dependent on the presence of a fluorine at position C-6 and was enhanced by the presence of a methyl group at C-5 or an azabicyclohexane at C-7. A nucleophilic substituent at C-8 was essential for the activity of gatifloxacin and moxifloxacin.

In Vitro Activity of Phytocannabinoids from High Potency Cannabis sativa

Planta Medica ◽  
2012 ◽  
Vol 78 (05) ◽  
Author(s):  
A Husni ◽  
S Ross ◽  
O Dale ◽  
C Gemelli ◽  
G Ma ◽  
...  
Keyword(s):  
Cannabis Sativa ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
High Potency
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