Triptolide: structural modifications, structure–activity relationships, bioactivities, clinical development and mechanisms

2012 ◽  
Vol 29 (4) ◽  
pp. 457 ◽  
Author(s):  
Zhao-Li Zhou ◽  
Ya-Xi Yang ◽  
Jian Ding ◽  
Yuan-Chao Li ◽  
Ze-Hong Miao
Keyword(s):  
Clinical Development ◽  
Structural Modifications ◽  
Structure Activity Relationships ◽  
Structure Activity

scholarly journals Comparison of the behavioral effects of mescaline analogs using the head twitch response in mice

2019 ◽  
Vol 33 (3) ◽  
pp. 406-414 ◽  
Author(s):  
Adam L Halberstadt ◽  
Muhammad Chatha ◽  
Stephen J Chapman ◽  
Simon D Brandt
Keyword(s):  
Systematic Investigation ◽  
Alkoxy Group ◽  
Structural Modifications ◽  
Head Twitch ◽  
Structure Activity Relationships ◽  
Twitch Response ◽  
Distinct Structure ◽  
Structure Activity ◽  
Methoxy Substituent ◽  
Head Twitch Response

Background: In recent years, there has been increasing scientific interest in the effects and pharmacology of serotonergic hallucinogens. While a large amount of experimental work has been conducted to characterize the behavioral response to hallucinogens in rodents, there has been little systematic investigation of mescaline and its analogs. The hallucinogenic potency of mescaline is increased by α-methylation and by homologation of the 4-methoxy group but it not clear whether these structural modifications have similar effects on the activity of mescaline in rodent models. Methods: In the present study, the head twitch response (HTR), a 5-HT2A receptor-mediated behavior induced by serotonergic hallucinogens, was used to assess the effects of mescaline and several analogs in C57BL/6J mice. HTR experiments were conducted with mescaline, escaline (4-ethoxy-3,5-dimethoxyphenylethylamine) and proscaline (3,5-dimethoxy-4-propoxyphenylethylamine), their α-methyl homologs TMA (3,4,5-trimethoxyamphetamine), 3C-E (4-ethoxy-3,5-dimethoxyamphetamine) and 3C-P (3,5-dimethoxy-4-propoxyamphetamine), and the 2,4,5-substituted regioisomers TMA-2 (2,4,5-trimethoxyamphetamine), MEM (4-ethoxy-2,5-dimethoxyamphetamine) and MPM (2,5-dimethoxy-4-propoxyamphetamine). Results: TMA induced the HTR and was twice as potent as mescaline. For both mescaline and TMA, replacing the 4-methoxy substituent with an ethoxy or propoxy group increased potency in the HTR assay. By contrast, although TMA-2 also induced the HTR with twice the potency of mescaline, potency was not altered by homologation of the 4-alkoxy group in TMA-2. Conclusions: The potency relationships for these compounds in mice closely parallel the human hallucinogenic data. These findings are consistent with evidence that 2,4,5- and 3,4,5-substituted phenylalkylamine hallucinogens exhibit distinct structure-activity relationships. These results provide additional evidence that the HTR assay can be used to investigate the structure-activity relationships of serotonergic hallucinogens.

Structure–activity relationships of triazolopyridine oxazole p38 inhibitors: Identification of candidates for clinical development

2006 ◽  
Vol 16 (16) ◽  
pp. 4339-4344 ◽  
Author(s):  
Kim F. McClure ◽  
Michael A. Letavic ◽  
Amit S. Kalgutkar ◽  
Christopher A. Gabel ◽  
Laurent Audoly ◽  
...  
Keyword(s):  
Clinical Development ◽  
Structure Activity Relationships ◽  
Structure Activity

Advances on the Bioactivities, Total Synthesis, Structural Modification, and Structure-Activity Relationships of Cytisine Derivatives

2020 ◽  
Vol 20 (5) ◽  
pp. 369-395 ◽  
Author(s):  
Xiaobo Huang ◽  
Hui Xu
Keyword(s):  
Smoking Cessation ◽  
Total Synthesis ◽  
Structural Modification ◽  
Biological Properties ◽  
Structural Modifications ◽  
Structure Activity Relationships ◽  
Quinolizidine Alkaloid ◽  
Cytisine Derivatives ◽  
Structure Activity ◽  
Lactam Ring

Cytisine is a quinolizidine alkaloid isolated from various Leguminosae plants. Cytisine and its derivatives exhibit a broad range of biological properties, such as smoking cessation aid, antidepressant, neuroprotective, nootropic, anticancer, antiviral, antiparasitic, antidiabetic, insecticidal, and nematicidal activities. In this review, the progress of cytisine and its derivatives in regard to bioactivities, total synthesis, structural modifications focusing on their N-12 position and lactam ring is reported. Additionally, the structure-activity relationships of cytisine and its derivatives are also discussed.

scholarly journals A Template-Based Approach for Guiding and Refining the Development of Cinnamon-Based Phenylpropanoids as Drugs

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4629
Author(s):  
Ngoc Uy Nguyen ◽  
Brendan David Stamper
Keyword(s):  
Gene Expression ◽  
Effective Means ◽  
Cost Effective ◽  
Receptor Interaction ◽  
Individual Treatment ◽  
Template Effect ◽  
Structural Modifications ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Biologic Activity

Background: Structure-activity relationships describe the relationship between chemical structure and biologic activity and are capable of informing deliberate structural modifications to a molecule in order enhance drug properties. Methods: Here, we present a subtle, yet unique twist on structure-activity relationships in which a collective biologic activity was measured among five cinnamon constituents with a shared phenylpropanoid template (cinnamic acid, cinnamaldehyde, chlorogenic acid, caffeic acid, and ferulic acid). This template-based approach utilized publicly available transcriptomic data through the Gene Expression Omnibus (GEO) to identify a fundamental biologic effect; in essence, a phenylpropanoid template effect. Results: The recurrent identification of cytokine-cytokine receptor interaction and neuroactive ligand receptor pathways in each individual treatment condition strongly supports the fact that changes in gene expression within these pathways is a hallmark of the phenylpropanoid template. With a template effect identified, future structural modifications can be performed in order to overcome pharmacokinetic barriers to clinical use (i.e., traditional structure-activity relationship experiments). Moreover, these modifications can be implemented with a high degree of confidence knowing that a consistent and robust template effect is likely to persist. Conclusion: We believe this template-based approach offers researchers an attractive and cost-effective means for evaluating multicomponent natural products during drug development.

Structure–activity relationships for ruthenium and osmium anticancer agents – towards clinical development

2018 ◽  
Vol 47 (3) ◽  
pp. 909-928 ◽  
Author(s):  
Samuel M. Meier-Menches ◽  
Christopher Gerner ◽  
Walter Berger ◽  
Christian G. Hartinger ◽  
Bernhard K. Keppler
Keyword(s):  
Drug Discovery ◽  
Anticancer Agents ◽  
Clinical Development ◽  
Global Structure ◽  
Discovery Process ◽  
Drug Discovery Process ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Anticancer Therapeutics

The drug discovery process of ruthenium and osmium anticancer therapeutics is described, including global structure–activity relationships.

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