Translation of In Vitro Activity to In Vivo Activity: Lessons from the Triazolopyrimidine Sulfonanilides

Weed Science ◽  
1996 ◽  
Vol 44 (3) ◽  
pp. 757-762 ◽  
Author(s):  
B. Clifford Gerwick ◽  
Csaba T. Cseke ◽  
Gerry Deboer ◽  
William A. Kleschick ◽  
Paul R. Schmitzer
Keyword(s):  
Acetolactate Synthase ◽  
Metabolic Stability ◽  
Plant Structure ◽  
Weed Species ◽  
Whole Plant ◽  
Stability Data ◽  
Activity Models ◽  
Two Parameter

Eight triazolopyrimidine sulfonanilides were tested for metabolic stability in a number of crop and weed species. These data, along with in vitro determinations of activity (I50) against acetolactate synthase, successfully described the in vivo activity of these compounds in a two-parameter model. Whole plant activity increased with increasing compound stability and decreasing I50 (r2 =.78, N = 36). The difficulty in obtaining metabolic stability data during a structure optimization program prompted a study with substituent parameters in models of in vivo activity. Models describing whole plant activity in jimsonweed were developed using a series of 5-methyl triazolopyrimidine sulfonanilides that differed only in ortho and meta substituents on the aniline ring. The I50 term and clogP were most important to jimsonweed activity. Hence, in vitro activity (I50) may be a useful component of whole plant structure activity models to aid in identification of barriers to in vivo performance.

Nyctanthes Arbor-Tristis and its Role in the Alleviation of Arthritic Pain: A Review

2020 ◽  
Vol 16 (8) ◽  
pp. 1147-1156
Author(s):  
Ruchi Singh ◽  
Syed M. Hasan ◽  
Amit Verma ◽  
Sanjay K. Panda
Keyword(s):  
Research Work ◽  
Plant Distribution ◽  
Pharmacological Activities ◽  
Whole Plant ◽  
Modern Drug ◽  
Active Chemical ◽  
Drug Synthesis ◽  
New Compounds

Background: A plant is a reservoir of potentially useful active chemical entities which act as drugs as well as intermediates for the discovery of newer molecules and provide newer leads for modern drug synthesis. The demand for new compounds in the field of medicine and biotechnology is centuries old and with a rise in chronic diseases and resistance to existing drugs in the field of anti-infective agents, the chemicals obtained from plant sources have been an area of attraction. The whole plant has possessed multiple pharmacological activities. This is scientifically established by in-vivo and in-vitro studies. Methods: Various electronic databases such as PubMed, Science Direct, Scopus and Google were searched to collect the data of the present review. All the collected information is categorized into different sections as per the aim of the paper. Results: Fifty-six research and review papers have been studied and were included in this review article. After a detailed study, we provide a significant description of various phytochemicals present in Nyctanthes arbor-tristis Linn., which is responsible for various pharmacological activities. Twenty of studied articles gives a general introduction and ethnobotanical information about the plant, two papers contained microscopic detail of leaf and fruit. Twenty papers contained information about the phytoconstituents present in different parts of Nyctanthes arbor-tristis plant and fourteen articles reported pharmacological activities like antioxidant, anti-inflammatory, antiarthritic, antimicrobial and immunobiotic activity. Conclusion: This review explores the published research work comprising the ethnobotanical description of the subjected plant, distribution, phytochemical profile, and arthritis-related pharmacological activities.

Common Cocklebur (Xanthium strumarium) Resistance to Selected ALS-Inhibiting Herbicides

1997 ◽  
Vol 11 (2) ◽  
pp. 241-247 ◽  
Author(s):  
Christy L. Sprague ◽  
Edward W. Stoller ◽  
Loyd M. Wax
Keyword(s):  
Acetolactate Synthase ◽  
Cross Resistance ◽  
Xanthium Strumarium ◽  
Laboratory Studies ◽  
Whole Plant ◽  
Plant Level

Five biotypes of common cocklebur that were not controlled with acetolactate synthase (ALS)-inhibiting herbicides were tested in greenhouse and laboratory studies to determine the magnitude of resistance and cross-resistance to four ALS-inhibiting herbicides. In vivo inhibition of ALS was also evaluated. Based on phytotoxicity, all five ALS-resistant biotypes of common cocklebur were > 390 times more resistant than the susceptible biotype to imazethapyr. However, only four of these biotypes were also resistant to another imidazolinone, imazaquin. Two biotypes were cross-resistant to the sulfonylurea, chlorimuron, and the triazolopyrimidine sulfonanilide, NAF-75. One biotype demonstrated intermediate susceptibility to imazaquin, chlorimuron, and NAF-75. In all cases, the resistance exhibited at the whole plant level was associated with an insensitive ALS.

scholarly journals Swertiamarin Contributes to Glucose Homeostasis via Inhibition of Carbohydrate Metabolizing Enzymes

2017 ◽  
Vol 16 (4) ◽  
pp. 125 ◽  
Author(s):  
Javed Ahamad ◽  
Naila Hassan ◽  
Saima Amin ◽  
Showkat R. Mir
Keyword(s):  
Blood Glucose ◽  
Glucose Homeostasis ◽  
In Vivo Studies ◽  
Metabolizing Enzymes ◽  
Treatment Groups ◽  
Whole Plant ◽  
Peak Blood ◽  
Peak Blood Glucose

<strong>Objective:</strong> Swertiamarin is a common secoiridoid found among the members of Gentianaceae. The present study aimed to establish the effectiveness of swertiamarin in achieving glucose homeostasis via inhibition of carbohydrate metabolizing enzymes by in-vitro and in-vivo studies. <strong>Materials and methods:</strong> Swertiamarin was obtained from dried whole plant samples of <em>Enicostemma littorale</em> Blume chromatographic fractionation over the silica gel column. Its effect on carbohydrate metabolizing enzymes viz., α-amylase and α-glucosidase were evaluated at 0.15 to 10 mg/mL in-vitro. The results were supplemented by anti-hyperglycemic studies in carbohydrate challenged mice pretreated with swertiamarin at a dose of 20 mg/kg body weight orally. <strong>Results:</strong> Swertiamarin was effective in inhibiting α-amylase and α-glucosidase with IC<em>50</em> values of 1.29±0.25 mg/mL and 0.84±0.11 mg/mL, respectively. The studies in starch and sucrose challenged mice showed that swertiamarin effectively restricted the increase in the peak blood glucose level (BGL). The increase in peak BGL was 49 mg/dL and 57 mg/dL only in the treatment groups compared to 70 mg/dL and 80 mg/dL in untreated groups after 30 min in starch and sucrose-fed mice, respectively. Acarbose (10 mg/kg b.w.) also produced significant (p&lt;0.01) blood glucose lowering response in both the models. <strong>Conclusion:</strong> Swertiamarin was effective in the achieving stricter glycemic control in carbohydrate challenged mice through the inhibition of carbohydrate metabolizing enzymes.

scholarly journals In vitro and In vivo Antidiabetic Evaluation of Whole Plant Extracts of Argyreia imbricata (Roth) Sant. and Patel

2021 ◽  
Vol 13 (1) ◽  
pp. 30-36
Author(s):  
Sebastin V Sebastin ◽  
Gopalakrishnan G Gopalakrishnan ◽  
Sreejith M Sreejith ◽  
KI Anoob Kumar
Keyword(s):  
Plant Extracts ◽  
Whole Plant

Ethnobotany, Pharmacological activities and Bioavailability studies of “King of Bitter” (Kalmegh): A Review (2010-2020)

2021 ◽  
Vol 24 ◽  
Author(s):  
Sharuti Mehta ◽  
Anil Kumar Sharma ◽  
Rajesh Kumar Singh
Keyword(s):  
Research Work ◽  
General Information ◽  
Future Research ◽  
Herbaceous Plant ◽  
Active Metabolites ◽  
Pharmacological Activities ◽  
Whole Plant ◽  
Pure Compounds

Background: Andrographis paniculata, commonly known as “Kalmegh”, is an annual herbaceous plant from family Acanthaceae. The whole plant of A. paniculata has explored for multiple pharmacological activities and is scientifically recognized by in-vivo and in-vitro studies. Various biotechnologically engineered techniques have been explored to enhance the bioavailability of this plant. Objective: In this review, we aim to present comprehensive recent advances in the ethnopharmacology, phytochemistry, specific pharmacology, safety and toxicology and bioavailability of A. paniculata and its pure compounds. Possible directions for future research are also outlined in brief, which will encourage advance investigations on this plant. Methods: Information on the recent updates of the present review is collected from different electronic scientific databases such as Science Direct, PubMed, Scopus, and Google Scholar. All the composed information is classified into different sections according to the objective of the paper. Results: More than hundred research and review papers have been studied and incorporated in the present manuscript. After vast literature search of A. paniculata, we present a noteworthy report of various phytoconstituents present in plant, which are accountable for potential therapeutic properties of the plant. Forty-five of studied articles give general information about introduction, ethnobotany and traditional uses of the plant. Twenty-two papers enclosed information about the phytoconstituents present in different parts of A. paniculata and seventy-two papers briefly outlined the pharmacological activities like antioxidant, anti-dengue, anti-ulcerogenic, antifungal, some miscellaneous activities like activity against SARS-CoV-2, antidiarrhoeal. Nineteen studies highlighted the research work conducted by various researchers to increased bioavailability of A. paniculata and two studies reported the safety and toxicology of the plant. Conclusion: This review incorporated the scientifically validated research work encompassing the ethnobotanical description of the subjected plant, phytochemical profile, various pharmacological activities, and recent approaches to enhance the bioavailability of active metabolites.

scholarly journals Brain Delivery of Thyrotropin-Releasing Hormone via a Novel Prodrug Approach

Pharmaceutics ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 349 ◽  
Author(s):  
Katalin Prokai-Tatrai ◽  
Daniel L. De La Cruz ◽  
Vien Nguyen ◽  
Benjamin P. Ross ◽  
Istvan Toth ◽  
...  
Keyword(s):  
Brain Homogenate ◽  
Thyrotropin Releasing Hormone ◽  
Metabolic Stability ◽  
Antidepressant Effect ◽  
Brain Delivery ◽  
Small Peptides ◽  
Releasing Hormone ◽  
Membrane Affinity

Using thyrotropin-releasing hormone (TRH) as a model, we explored whether synergistic combination of lipoamino acid(s) and a linker cleaved by prolyl oligopeptidase (POP) can be used as a promoiety for prodrug design for the preferential brain delivery of the peptide. A representative prodrug based on this design principle was synthesized, and its membrane affinity and in vitro metabolic stability, with or without the presence of a POP inhibitor, were studied. The in vivo formation of TRH from the prodrug construct was probed by utilizing the antidepressant effect of the peptide, as well as its ability to increase acetylcholine (ACh) synthesis and release. We found that the prototype prodrug showed excellent membrane affinity and greatly increased metabolic stability in mouse blood and brain homogenate compared to the parent peptide, yet a POP inhibitor completely prevented prodrug metabolism in brain homogenate. In vivo, administration of the prodrug triggered antidepressant-like effect, and microdialysis sampling showed greatly increased ACh release that was also antagonized upon a POP inhibitor treatment. Altogether, the obtained promising exploratory data warrant further investigations on the utility of the prodrug approach introduced here for brain-enhanced delivery of small peptides with neurotherapeutic potential.

Thermal dependence of pyrithiobac efficacy inAmaranthus palmeri

Weed Science ◽  
1999 ◽  
Vol 47 (6) ◽  
pp. 644-650 ◽  
Author(s):  
Ginger G. Light ◽  
Peter A. Dotray ◽  
James R. Mahan
Keyword(s):  
Weed Control ◽  
Acetolactate Synthase ◽  
Field Studies ◽  
Thermal Dependence ◽  
Growing Seasons ◽  
Air Temperatures ◽  
Whole Plant ◽  
Crude Leaf Extract ◽  
Highly Correlated

Variability in weed control following pyrithiobac applications has been observed under field conditions. The influence of temperature on this variability was investigated. Results from field studies performed over two growing seasons identified plant and air temperatures at the time of herbicide treatment that correlated with whole-plant efficacy differences. Based on the field data, weed control with pyrithiobac was acceptable at application temperatures of 20 to 34 C. To investigate a potential source of thermal limitations on pyrithiobac efficacy, the thermal dependence of in vitro inhibition of acetolactate synthase (ALS), the site of action for pyrithiobac, was examined. A crude leaf extract of ALS was obtained fromAmaranthus palmeri. Relative inhibitor potency (I50) values were obtained at saturating substrate conditions for temperatures from 10 to 50 C. Regression analysis of field activity against I50values showed the two data sets to be highly correlated (R2= 0.88). The thermal dependence of enzyme/herbicide interactions may provide another means of understanding environmental factors limiting herbicidal efficacy and predicting herbicide inhibition at the whole-plant level.

Sign in / Sign up

Export Citation Format

Share Document