ADMET properties of novel 5-O-benzoylpinostrobin derivatives

2019 ◽  
Vol 30 (6) ◽  
Author(s):  
Mohammad Rizki Fadhil Pratama ◽  
Hadi Poerwono ◽  
Siswandono Siswodiharjo
Keyword(s):  
Androgen Receptor ◽  
Cytotoxic Activity ◽  
Blood Brain Barrier ◽  
Inhibitory Activity ◽  
Water Solubility ◽  
Nitro Derivative ◽  
Total Clearance ◽  
Distribution Parameters ◽  
Trifluoromethyl Derivative ◽  
Class Iv

Abstract Background Prediction of the properties of absorption, distribution, metabolism, excretion, and toxicity (ADMET) from a compound is essential, especially for modified novel compounds. Previous research has successfully designed several modified compounds of 5-O-benzoyl derivatives from pinostrobin, a flavanone that has cytotoxic activity. This study aims to describe the properties of ADMET from the 5-O-benzoylpinostrobin derivative. Methods Prediction of the properties of ADMET was carried out using three web servers consisting of SwissADME, pkCSM, and ProTox-II. The observed parameters are divided into ADMET parameters. Results In general, absorption parameters indicate that the 5-O-benzoylpinostrobin derivative has lower water solubility than the parent pinostrobin. Distribution parameters show mixed results for distribution through the blood-brain barrier. Metabolism parameters showed different results with generally inhibitory activity shown in CYP2C19, CYP2C9, and CYP3A4. The excretion parameters showed a higher total clearance than pinostrobin except in the trifluoromethyl derivative. The toxicity parameters showed both pinostrobin and the 5-O-benzoylpinostrobin derivatives, including the class IV toxicity category with the lowest LD50 value indicated by the nitro derivative of 1500, with the possible target of the androgen receptor and prostaglandin G/H synthase 1. Conclusions Overall, the 5-O-benzoylpinostrobin derivative has the predicted ADMET profile that is relatively similar to pinostrobin, with the most noticeable difference being shown in the absorption parameters where all 5-O-benzoylpinostrobin derivatives have lower water solubility than pinostrobin.

scholarly journals Ingol and Ingenol-Type Diterpenes from Euphorbia trigona Miller with Keratinocyte Inhibitory Activity

Plants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1206
Author(s):  
Reham Hammadi ◽  
Norbert Kúsz ◽  
Csilla Zsuzsanna Dávid ◽  
Zoltán Behány ◽  
László Papp ◽  
...  
Keyword(s):  
Liquid Chromatography ◽  
Cytotoxic Activity ◽  
Inhibitory Activity ◽  
High Performance ◽  
Skin Condition ◽  
Positive Control ◽  
Active Species ◽  
The European Union ◽  
Ingenol Mebutate

Ingenol mebutate, isolated from Euphorbia peplus, is an ingenane-type diterpenoid, primarily used for the topical treatment of actinic keratosis, a premalignant skin condition. The aim of our work was to investigate other Euphorbia species to find structurally similar diterpenes that can be used as alternatives to ingenol mebutate. Pharmacological investigation of Euphorbia candelabrum, Euphorbia cotinifolia, Euphorbia ramipressa, and Euphorbia trigona revealed the potent keratinocyte (HPV-Ker cell line) inhibitory activity of these spurge species. From the methanolic extract of the aerial parts of Euphorbia trigona Miller, the most active species, five ingol (1–5) and four ingenane-type diterpenoids (6–9) were isolated by various chromatographic separation techniques, including open column chromatography, vacuum liquid chromatography, thin-layer chromatography, and high-performance liquid chromatography. The structures of the compounds were determined by NMR spectroscopic analysis and by comparison of the assignations with the literature data. The cytotoxic activity of the compounds against keratinocytes was tested in vitro by using ingenol mebutate as a positive control. Among the isolated compounds, two ingenane derivatives (6 and 7) exhibited remarkably stronger cytotoxic activity (IC50 values 0.39 μM and 0.32 μM, respectively) on keratinocytes than ingenol mebutate (IC50 value 0.84 μM). These compounds could serve as starting materials for further investigations to find alternatives to Picato® (with active substance ingenol mebutate), which was withdrawn from marketing authorization in the European Union.

In Vitro Androgen Receptor Binding Affinity and in Vivo Inhibitory Activity of 5?-Pregnane-3, 20-Dione

1988 ◽  
Vol 529 (1 Fourth Colloq) ◽  
pp. 239-241
Author(s):  
SAUDHAMINI PARTHASARATHY ◽  
ANDREA CHIN ◽  
VIRGINIA MALLOY ◽  
JONATHAN MATIAS
Keyword(s):  
Androgen Receptor ◽  
Binding Affinity ◽  
Receptor Binding ◽  
Inhibitory Activity ◽  
Receptor Binding Affinity

scholarly journals New Humulenes from Hyptis incana (Labiatae)

2013 ◽  
Vol 8 (12) ◽  
pp. 1934578X1300801
Author(s):  
Mitsuru Satoh ◽  
Yoshio Satoh ◽  
Yasuhiro Anzai ◽  
Daisuke Ajisawa ◽  
Keiichi Matsuzaki ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Inhibitory Activity ◽  
Leukemia Cells ◽  
Moderate Activity ◽  
Mouse Leukemia ◽  
Aerial Parts ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
Potent Growth

Two new humulene-type sesquiterpenes, named hyptishumulene I (1) and II (2), have been isolated, together with eight known compounds, a humulene-type sesquiterpene (3), a monoterpene (4) and six abietane-type diterpenoids (5–10) from the aerial parts of Hyptis incana (Labiatae). The cytotoxic activity of the isolated compounds against mouse leukemia cells (L1210) was examined. The abietane-type diterpenoids (5–10) showed rather potent growth inhibitory activity (IC50<15 μM), while the new humulene-type compounds (1 and 2) exhibited moderate activity (IC50>50 μM).

Synthesis, cytotoxic activity, and tubulin polymerization inhibitory activity of new pyrrol-2(3H)-ones and pyridazin-3(2H)-ones

2016 ◽  
Vol 66 ◽  
pp. 46-62 ◽  
Author(s):  
Samar Hafez Abbas ◽  
Gamal El-Din A.A. Abuo-Rahma ◽  
Mohamed Abdel-Aziz ◽  
Omar M. Aly ◽  
Eman A. Beshr ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Inhibitory Activity ◽  
Tubulin Polymerization

scholarly journals Anti-proliferative Activity of Some Oleanolic Acid Derivatives with Potent Topoisomerase Inhibitory Activity on B16 Melanoma Cells

2020 ◽  
Vol 9 (1) ◽  
pp. 26-28
Author(s):  
Ahmed Ashour ◽  
Ryuichiro Kondo ◽  
Kuniyoshi Shimizu
Keyword(s):  
Cytotoxic Activity ◽  
Oleanolic Acid ◽  
Anticancer Agents ◽  
Inhibitory Activity ◽  
Topoisomerase I ◽  
Melanoma Cells ◽  
Docking Studies ◽  
B16 Melanoma ◽  
Melanoma Cancer ◽  
B16 Melanoma Cells

Our previous study included the semisynthetic reactions on oleanolic acid, a common wood-derived oleanane-type triterpene. Ten rationally designed derivatives of oleanolic acid were synthesized based on docking studies and tested for their topoisomerase I and IIα inhibitory activity. Semisynthetic reactions targeted C-3, C-12, C-13 and C-17. Some of these compounds act as dual inhibitors for both topoisomerase I and IIα giving new anticancer agents. The cytotoxic activity of these compounds on B16 melanoma cancer cells was evaluated. Results showed that most of these compounds have a higher cytotoxic activity on B16 melanoma cells.

Lipid Nanoformulations in the Treatment of Neuropsychiatric Diseases: An Approach to Overcome the Blood Brain Barrier

2020 ◽  
Vol 21 (9) ◽  
pp. 674-684 ◽  
Author(s):  
Saleha Rehman ◽  
Bushra Nabi ◽  
Faheem Hyder Pottoo ◽  
Sanjula Baboota ◽  
Javed Ali
Keyword(s):  
Blood Brain Barrier ◽  
Water Solubility ◽  
Oral Absorption ◽  
Brain Barrier ◽  
Therapeutic Drug ◽  
Blood Brain ◽  
Neuropsychiatric Diseases ◽  
The Brain

Background: Neuropsychiatric diseases primarily characterized by dementia stand third in the global list of diseases causing disability. The poor water solubility, erratic oral absorption, low bioavailability, poor intestinal absorption, and the impeding action of the blood-brain barrier (BBB) are the major factors limiting the therapeutic feasibility of the antipsychotics. Only a small percentage of antipsychotics reaches the therapeutic target site, which warrants administration of high doses, consequently leading to unwanted side-effects. Hence the main struggle for the effective treatment of neuropsychiatric diseases occurs “at the gates” of the brain, which can be mitigated with the use of a nanotechnology-based platform. Methods: The goal of this review is to undertake a comprehensive study about the role of lipid nanoformulations in facilitating the delivery of antipsychotics across BBB along with the available in vitro and in vivo evidence. Results: Lipid nanoformulations have attained great popularity for the delivery of therapeutics into the brain. Their nanosize helps in overcoming the biological barriers, thereby providing easy BBB translocation of the drugs. Besides, they offer numerous advantages like controlled and targeted drug release, minimizing drug efflux, long storage stability, augmented bioavailability, and reduced adverse drug effects to attain an optimal therapeutic drug concentration in the brain. Moreover, employing alternative routes of administration has also shown promising results. Conclusion: Thus, it can be concluded that the lipid nanoformulations bear immense potential in overcoming the challenges associated with the treatment of neuropsychiatric disorders. However, the area warrants further clinical studies to ensure their commercialization, which could revolutionize the treatment of neuropsychiatric diseases in the coming decades.

scholarly journals Bergamot essential oil nanoemulsions: antimicrobial and cytotoxic activity

2020 ◽  
Vol 75 (7-8) ◽  
pp. 279-290
Author(s):  
Enrico Marchese ◽  
Nunzia D’onofrio ◽  
Maria Luisa Balestrieri ◽  
Domenico Castaldo ◽  
Giovanna Ferrari ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Essential Oil ◽  
Cytotoxic Activity ◽  
Water Solubility ◽  
Physical Stability ◽  
Food Preservation ◽  
Lactobacillus Delbrueckii ◽  
Hydrodynamic Diameter ◽  
Anticancer Efficacy ◽  
Micro Organisms

AbstractBergamot essential oil (BEO) is well-known for its food preservation activity, as well as anticancer efficacy. However, the poor BEO water solubility and deriving low bioaccessibility have limited its wider applications. The incorporation in nanoemulsions of BEO and its refined fractions was investigated to enhance its dispersibility in water to promote its antimicrobial activity, tested against Escherichia coli, Lactobacillus delbrueckii, and Saccharomyces cerevisiae, and its cytotoxicity already at low concentrations. Different nanoemulsion formulations were tested based on food-grade ingredients, which were characterized in terms of hydrodynamic diameter and polydispersity index, and physical stability. The antimicrobial activity against all the tested micro-organisms was observed to be higher for BEO in its initial composition, than the light fraction, richer in d-limonene, ß-pinene, and γ-terpinene, or the heavy fraction, richer in linalyl acetate and linalool. Remarkably, the use of BEO nanoemulsions notably enhanced the antimicrobial activity for all the tested oils. BEO exhibited also a measurable cytotoxic activity against Caco-2 cells, which was also enhanced by the use of the different nanoemulsions tested, in comparison with free oil, which discourages the direct use of BEO nanoemulsions as a food preservative. Conversely, BEO nanoemulsions might find use in therapeutic applications as anticarcinogenic agents.

scholarly journals IN VITRO CYTOTOXIC ACTIVITY OF SECOISOLARICIRESINOL DIGLUCOSIDE ON HT-29, PA-1 CELL LINES, AND α-AMYLASE INHIBITORY ACTIVITY

2019 ◽  
pp. 168-173
Author(s):  
GUNABHUSHANA DADDALA ◽  
SWAROOPARANI A
Keyword(s):  
Cytotoxic Activity ◽  
Cell Line ◽  
Cancer Cell ◽  
Inhibitory Activity ◽  
Ovarian Cancer Cell Line ◽  
Cancer Cell Line ◽  
Secoisolariciresinol Diglucoside ◽  
Human Colon Cancer ◽  
Ht 29

Objective: The present study was conducted to evaluate the in vitro cytotoxic activity and α- amylase inhibitory activity of secoisolariciresinol diglucoside (SDG). Methods: The cytotoxic activity was conducted on HT-29 (human colon cancer cell line) and PA-1 (human ovarian cancer cell line) by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and the α- amylase inhibitory activity using acarbose as a standard. Both the tests were evaluated at different concentrations, 3.125–100 μg/ml and 50–2000 μg correspondingly and the concentration required for a 50% inhibition of viability (IC50) was determined graphically. The effect of the samples on the proliferation of HT-29 and PA-1 was expressed as the percentage cell viability. Results: SDG exhibited a considerable dose- and time-dependent inhibition on both HT-29 and PA-1 and also observed a concentration-dependent α-amylase inhibitory activity that leads in reduction of starch hydrolysis and hence eventually to lowered glucose levels. Conclusion: The present in vitro study concluded that SDG can be a potent anticancer and moderate hyperglycemic component.

scholarly journals Synthesis of Daidzein Glycosides, α-Tocopherol Glycosides, Hesperetin Glycosides by Bioconversion and Their Potential for Anti-Allergic Functional-Foods and Cosmetics

Molecules ◽  
2019 ◽  
Vol 24 (16) ◽  
pp. 2975
Author(s):  
Yuya Fujitaka ◽  
Hiroki Hamada ◽  
Daisuke Uesugi ◽  
Atsuhito Kuboki ◽  
Kei Shimoda ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Water Solubility ◽  
Biological Activities ◽  
Biological Effects ◽  
Physicochemical Stability ◽  
Peritoneal Mast Cells ◽  
Anti Cancer ◽  
New Compounds ◽  
Poor Absorption ◽  
Anti Inflammation

Daidzein is a common isoflavone, having multiple biological effects such as anti-inflammation, anti-allergy, and anti-aging. α-Tocopherol is the tocopherol isoform with the highest vitamin E activity including anti-allergic activity and anti-cancer activity. Hesperetin is a flavone, which shows potent anti-inflammatory effects. These compounds have shortcomings, i.e., water-insolubility and poor absorption after oral administration. The glycosylation of bioactive compounds can enhance their water-solubility, physicochemical stability, intestinal absorption, and biological half-life, and improve their bio- and pharmacological properties. They were transformed by cultured Nicotiana tabacum cells to 7-β-glucoside and 7-β-gentiobioside of daidzein, and 3′- and 7-β-glucosides, 3′,7-β-diglucoside, and 7-β-gentiobioside of hesperetin. Daidzein and α-tocopherol were glycosylated by galactosylation with β-glucosidase to give 4′- and 7-β-galactosides of daidzein, which were new compounds, and α-tocopherol 6-β-galactoside. These nine glycosides showed higher anti-allergic activity, i.e., inhibitory activity toward histamine release from rat peritoneal mast cells, than their respective aglycones. In addition, these glycosides showed higher tyrosinase inhibitory activity than the corresponding aglycones. Glycosylation of daidzein, α-tocopherol, and hesperetin greatly improved their biological activities.

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