scholarly journals Structure-Activity-Relationship and Bioactivity of Neurotrophic trans-Banglene

2021 ◽  
Author(s):  
Khyati Gohil ◽  
M. Zain Kazmi ◽  
Florence Williams
Keyword(s):  
Kinase Inhibitors ◽  
Signaling Proteins ◽  
Structure Activity ◽  
Cyclohexene Ring ◽  
Pharmacokinetic Properties ◽  
Living Organisms ◽  
Neurotrophic Signaling ◽  
Cis And Trans ◽  
The Relationship ◽  
Phenotypic Responses

Neurotrophic small molecule natural products are functional analogs of signaling proteins called neurotrophins, which cause a pro-growth, pro-survival, or pro-differentiation response in neuronal cells. While these phenotypic responses are desirable to combat neurodegenerative disease progression, neurotrophin proteins possess pharmacokinetic properties that present challenges to their administration in living organisms, whether in biomedical studies or as therapeutics. Small molecules such as the cis- and trans-banglenes offer attractive alternatives to activate neurotrophic responses. We describe the synthesis and testing of banglene derivatives to establish a structure-activity response for the banglene family. Notably, during the course of our studies trans-banglene was shown to cause nerve growth factor (NGF)-potentiated neuritogenesis that was markedly stronger than the neuritogenic effects of trans-banglene alone. We demonstrate that only (–) trans-banglene is active, while its (+) enantiomer is not, and further demonstrate that select modifications on the cyclohexene ring of trans-banglene does not impair its bioactivity. Finally, to probe the relationship between (–) trans-banglene’s mechanism of ac-tion and canonical NGF signal transduction pathways, we employed kinase inhibitors targeting Pkc, Akt1/2/3 and Erk1/2, designed to inhibit NGF-induced neurotrophic signaling. Interestingly, (–) trans-banglene potentiation of NGF-induced neuri-togenesis was unaffected by the presence of these kinase inhibitors. Collectively, these results suggest a dual-mode of action for (–) trans-banglene (both neurotrophic alone and strongly potentiating of NGF activity), and an independence of its po-tentiating action on Pkc and Erk1/2 enzymatic activity.

scholarly journals Structure-Activity-Relationship and Bioactivity of Neurotrophic trans-Banglene

2021 ◽  
Author(s):  
Khyati Gohil ◽  
M. Zain Kazmi ◽  
Florence Williams
Keyword(s):  
Small Molecules ◽  
Small Molecule ◽  
Signaling Proteins ◽  
Neurotrophic Activity ◽  
Structure Activity ◽  
Cyclohexene Ring ◽  
Pharmacokinetic Properties ◽  
Pkc Inhibitors ◽  
Cis And Trans ◽  
Phenotypic Responses

Neurotrophic small molecule natural products are functional analogs of signaling proteins called neurotrophins, which cause a pro-growth, pro-survival, or pro-differentiation response in neuronal cells. While these phenotypic responses are desirable to combat neurodegenerative disease progression, the pharmacokinetic properties of neurotrophins present challenges to their administration. Therefore, neurotrophic small molecules such as the cis- and trans-banglenes offer attractive alternatives. We describe the synthesis and testing of banglene derivatives and establish a structure-activity response for the banglene family. We demonstrate that (–) trans-banglene is the primarily active enantiomer, and that select modifications on the cyclohexene ring of trans-banglene do not significantly impair its bioactivity. Finally, we demonstrate that (–) trans-banglene potentiation of NGF induced neuritogenesis is unaffected by the presence of these Erk1/2, Akt and Pkc inhibitors. Our structure-activity results also suggest that (–) trans-banglene neurotrophic activity and its potentiation of NGF activity might be distinct unassociated processes.

scholarly journals Structure-Activity Relationship and Bioactivity Studies of Neurotrophic trans-Banglene

2021 ◽  
Author(s):  
Khyati Gohil ◽  
M. Zain Kazmi ◽  
Florence Williams
Keyword(s):  
Small Molecules ◽  
Small Molecule ◽  
Signaling Proteins ◽  
Neurotrophic Activity ◽  
Structure Activity ◽  
Cyclohexene Ring ◽  
Pharmacokinetic Properties ◽  
Pkc Inhibitors ◽  
Cis And Trans ◽  
Phenotypic Responses

Neurotrophic small molecule natural products are functional analogs of signaling proteins called neurotrophins, which cause a pro-growth, pro-survival, or pro-differentiation response in neuronal cells. While these phenotypic responses are desirable to combat neurodegenerative disease progression, the pharmacokinetic properties of neurotrophins present challenges to their administration. Therefore, neurotrophic small molecules such as the cis- and trans-banglenes offer attractive alternatives. We describe the synthesis and testing of banglene derivatives and establish a structure-activity response for the banglene family. We demonstrate that (–) trans-banglene is the primarily active enantiomer, and that select modifications on the cyclohexene ring of trans-banglene do not significantly impair its bioactivity. Finally, we demonstrate that (–) trans-banglene potentiation of NGF induced neuritogenesis is unaffected by the presence of these Erk1/2, Akt and Pkc inhibitors. Our structure-activity results also suggest that (–) trans-banglene neurotrophic activity and its potentiation of NGF activity might be distinct unassociated processes.

Trypanocidal Structure-Activity Relationshipfor Cis- and Trans-methylpluviatolide

Planta Medica ◽  
2008 ◽  
Vol 74 (03) ◽  
Author(s):  
R Silva ◽  
J Saraiva ◽  
S Albuquerque ◽  
C Curti ◽  
PM Donate ◽  
...  
Keyword(s):  
Structure Activity ◽  
Cis And Trans

Synthesis, Antimalarial Evaluation and SAR Study of Some 1,3,5-Trisubstituted Pyrazoline Derivatives

2019 ◽  
Vol 16 (10) ◽  
pp. 807-817 ◽  
Author(s):  
Shilpy Aggarwal ◽  
Deepika Paliwal ◽  
Dhirender Kaushik ◽  
Girish Kumar Gupta ◽  
Ajay Kumar
Keyword(s):  
Antimalarial Activity ◽  
Analysis Data ◽  
Docking Study ◽  
Maximum Activity ◽  
Elemental Analysis Data ◽  
Mass Spectral ◽  
Structure Activity ◽  
Pharmacokinetic Properties ◽  
Sar Study

The synthesis of a novel series of 1,3,5-trisubstitiuted pyrazoline was achieved by refluxing chalcone derivative with different heteroaryl hydrazines. The newly synthesized compounds were characterized by 1H NMR, 13CNMR, mass spectral and elemental analysis data. The synthetic series of novel pyrazoline hybrids was screened for in vitro schizont maturation assay against chloroquine sensitive 3D7 strain of Plasmodium falciparum. Most of the compounds showed promising in vitro antimalarial activity against CQ sensitive strain. The preliminary structure-activity relationship study showed that quinoline substituted analog at position N-1 showed maximum activity followed by benzothiazole substitution, while phenyl substitution lowers the antimalarial activity. The observed activity was persistent by the docking study on P. falciparum cystein protease falcipain-2. The pharmacokinetic properties were also studied using ADME prediction.

A Review on Camptothecin Analogs with Promising Cytotoxic Profile

2019 ◽  
Vol 18 (13) ◽  
pp. 1796-1814 ◽  
Author(s):  
Sk. Abdul Amin ◽  
Nilanjan Adhikari ◽  
Tarun Jha ◽  
Shovanlal Gayen
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Structure Property ◽  
Cytotoxic Potential ◽  
Structure Property Relationships ◽  
Structure Activity ◽  
Camptothecin Analogs ◽  
Pharmacokinetic Properties ◽  
Quantitative Structure Activity Relationships

Camptothecin (CPT), obtained from Camptotheca acuminata (Nyssaceae), is a quinoline type of alkaloid. Apart from various traditional uses, it is mainly used as a potential cytotoxic agent acting against a variety of cancer cell lines. Though searches have been continued for last six decades, still it is a demanding task to design potent and cytotoxic CPTs. Different CPT analogs are synthesized to enhance the cytotoxic potential as well as to increase the pharmacokinetic properties of these analogs. Some of these analogs were proven to be clinically effective in different cancer cell lines. In this article, different CPT analogs have been highlighted extensively to get a detail insight about the structure-property relationships as well as different quantitative structure-activity relationships (QSARs) modeling of these analogs are also discussed. This study may be beneficial for designing newer CPT analogs in future.

scholarly journals Predicting Pharmacokinetic Properties of Potential Anticancer Agents via Their Chromatographic Behavior on Different Reversed Phase Materials

2021 ◽  
Vol 22 (8) ◽  
pp. 4257
Author(s):  
Małgorzata Janicka ◽  
Anna Mycka ◽  
Małgorzata Sztanke ◽  
Krzysztof Sztanke
Keyword(s):  
Liquid Chromatography ◽  
Anticancer Agents ◽  
Skin Permeation ◽  
Reversed Phase ◽  
Chromatographic Behavior ◽  
Chromatographic Retention ◽  
Quantitative Structure ◽  
Animal Testing ◽  
Structure Activity ◽  
Pharmacokinetic Properties

The Quantitative Structure-Activity Relationship (QSAR) methodology was used to predict biological properties, i.e., the blood–brain distribution (log BB), fraction unbounded in the brain (fu,brain), water-skin permeation (log Kp), binding to human plasma proteins (log Ka,HSA), and intestinal permeability (Caco-2), for three classes of fused azaisocytosine-containing congeners that were considered and tested as promising drug candidates. The compounds were characterized by lipophilic, structural, and electronic descriptors, i.e., chromatographic retention, topological polar surface area, polarizability, and molecular weight. Different reversed-phase liquid chromatography techniques were used to determine the chromatographic lipophilicity of the compounds that were tested, i.e., micellar liquid chromatography (MLC) with the ODS-2 column and polyoxyethylene lauryl ether (Brij 35) as the effluent component, an immobilized artificial membrane (IAM) chromatography with phosphatidylcholine column (IAM.PC.DD2) and chromatography with end-capped octadecylsilyl (ODS) column using aqueous solutions of acetonitrile as the mobile phases. Using multiple linear regression, we derived the statistically significant quantitative structure-activity relationships. All these QSAR equations were validated and were found to be very good. The investigations highlight the significance and possibilities of liquid chromatographic techniques with three different reversed-phase materials and QSARs methods in predicting the pharmacokinetic properties of our important organic compounds and reducing unethical animal testing.

scholarly journals Money, Agency, and Self-Care among Cisgender and Trans People in Sex Work

2020 ◽  
Vol 10 (1) ◽  
pp. 6
Author(s):  
Treena Orchard ◽  
Katherine Salter ◽  
Mary Bunch ◽  
Cecilia Benoit
Keyword(s):  
Drug Use ◽  
Social Services ◽  
Sex Work ◽  
Self Care ◽  
Internalized Stigma ◽  
Gender Analysis ◽  
Trans People ◽  
Safety And Health ◽  
Cis And Trans ◽  
The Relationship

Many qualitative studies about the exchange of sex for money, drugs, and less tangible outcomes (i.e., social status) contend that this activity contributes to high levels of internalized stigma among people in sex work. The cis (n = 33) and trans people (n = 5) who participated in our project about health, violence, and social services acknowledged the stigma associated with sex work but were not governed by the dominant discourse about its moral stain. They shared nuanced insights about the relationship between sex work and self-respect as people who use their earnings to mitigate the struggles of poverty and ongoing drug use, and care for themselves more broadly. This study sheds new light on the ways that cis and trans people negotiate issues of money, agency, and self-care, contributing to the literature on consensual sex work that examines different aspects of stigma, safety, and health with a nuanced, non-binary gender analysis.

Third-Generation and Investigational Cephalosporins: I. Structure-Activity Relationships and Pharmacokinetic Review

1983 ◽  
Vol 17 (7-8) ◽  
pp. 507-515 ◽  
Author(s):  
Pamela Garzone ◽  
James Lyon ◽  
Victor L. Yu
Keyword(s):  
Classification Scheme ◽  
Third Generation ◽  
Serum Concentrations ◽  
New Agents ◽  
The Third ◽  
Structure Activity ◽  
Pharmacokinetic Properties ◽  
Fluid Penetration ◽  
Third Generation Cephalosporins ◽  
Antibacterial Spectrum

The structure-relationships and pharmacokinetic properties of the new second- and third-generation cephalosporins are reviewed. The new second-generation cephalosporins include ceforanide, cefotiam, and cefuroxime. The third-generation cephalosporins include cefmenoxime, cefoperazone, cefotaxime, cefsulodin, ceftazidime, ceftizoxime, ceftriaxone, and moxalactam. These new cephalosporins are semisynthetic analogs with different chemical substitutions on a 7-aminocephalosporanic nucleus. As a result of these chemical modifications, improvements in the antibacterial spectrum as well as pharmacokinetic properties have occurred. In general, the new cephalosporins have longer half-lives, higher and prolonged serum concentrations, and increased cerebrospinal fluid penetration. Selected cephalosporins also have increased biliary tract concentrations. A classification scheme for these new agents, based on generation and susceptibility to Pseudomonas aeruginosa, is presented.

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