scholarly journals Bio-Potency and Molecular Docking Studies of Isolated Compounds from Grewia optiva J.R. Drumm. ex Burret

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 2019
Author(s):  
Wasim Ul Bari ◽  
Najeeb Ur Rehman ◽  
Ajmal Khan ◽  
Sobia Ahsan Halim ◽  
Ye Yuan ◽  
...  
Keyword(s):  
Radical Scavenging ◽  
Docking Studies ◽  
Drug Candidate ◽  
In Silico Docking ◽  
Ic50 Values ◽  
Grewia Optiva ◽  
New Compounds ◽  
First Time

In the study, two novel compounds along with two new compounds were isolated from Grewia optiva. The novel compounds have never been reported in any plant source, whereas the new compounds are reported for the first time from the studied plant. The four compounds were characterized as: 5,5,7,7,11,13-hexamethyl-2-(5-methylhexyl)icosahydro-1H-cyclopenta[a]chrysen-9-ol (IX), docosanoic acid (X), methanetriol mano formate (XI) and 2,2’-(1,4-phenylene)bis(3-methylbutanoic acid (XII). The anticholinesterase, antidiabetic, and antioxidant potentials of these compounds were determined using standard protocols. All the isolated compounds exhibited a moderate-to-good degree of activity against acetylcholinesterases (AChE) and butyrylcholinesterase (BChE). However, compound XII was particularly effective with IC50 of 55 μg/mL (against AChE) and 60 μg/mL (against BChE), and this inhibitory activity is supported by in silico docking studies. The same compound was also effective against DPPH (2, 2-diphenyl-1-picrylhydrazyl) and ABTS (2, 2′-azinobis-3-ethylbenzothiazoline-6-sulfonic acid) radicals with IC50 values of 60 and 62 μg/mL, respectively. The compound also significantly inhibited the activities of α-amylase and α-glucosidase in vitro. The IC50 values for inhibition of the two enzymes were recorded as 90 and 92 μg/mL, respectively. The in vitro potentials of compound XII to treat Alzheimer’s disease (in terms of AchE and BChE inhibition), diabetes (in terms of α-amylase and α-glucosidase inhibition), and oxidative stress (in terms of free radical scavenging) suggest further in vivo investigations of the compound for assessing its efficacy, safety profile, and other parameters to proclaim the compound as a potential drug candidate.

scholarly journals Hypoglycemic, hepatoprotective and molecular docking studies of 5-[(4-chlorophenoxy) methyl]-1, 3, 4-oxadiazole-2-thiol

2018 ◽  
Vol 13 (2) ◽  
pp. 149 ◽  
Author(s):  
Naureen Shehzadi ◽  
Khalid Hussain ◽  
Nadeem Irfan Bukhari ◽  
Muhammad Islam ◽  
Muhammad Tanveer Khan ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Video Clip ◽  
Serum Levels ◽  
Docking Studies ◽  
Normal Serum ◽  
Yeast Cells ◽  
Drug Candidate ◽  
Molecular Docking Studies

<p class="Abstract">The present study aimed at the evaluation of anti-hyperglycemic and hepatoprotective potential of a new drug candidate, 5-[(4-chlorophenoxy) methyl]-1,3,4-oxadiazole-2-thiol (OXCPM) through in vitro and in vivo assays, respectively. The compound displayed excellent dose-dependent ɑ-amylase (28.0-92.0%), ɑ-glucosidase (40.3-93.1%) and hemoglobin glycosylation (9.0%-54.9%) inhibitory effects and promoted the uptake of glucose by the yeast cells (0.2 to 26.3%). The treatment of the isoniazid- and rifampicin- (p.o., 50 mg/kg of each) intoxicated rats with OXCPM (100 mg/kg, p.o.) resulted in restoring the normal serum levels of the non-enzymatic (total bilirubin, total protein and albumin) and bringing about a remarkable decrease in the levels of enzymatic (alanine transaminases, aspartate transaminases and alkaline phosphatase) biomarkers. The molecular docking studies indicated high binding affinity of the compound for hyperglycemia-related protein targets; fructose-1,6-bisphosphatase, beta<sub>2</sub>-adrenergic receptors and glucokinase. The results indicate that OXCPM may not only reduce hyperglycemia by enzyme inhibition but also the disease complications through protection of hemoglobin glycosylation and hepatic injury.</p><p class="Abstract"><strong>Video Clip of Methodology:</strong></p><p class="Abstract">Glucose uptake by yeast cells:   4 min 51 sec   <a href="https://www.youtube.com/v/8cJkuMtV0Wc">Full Screen</a>   <a href="https://www.youtube.com/watch?v=8cJkuMtV0Wc">Alternate</a></p>

scholarly journals Oleuropein modulates over-proliferation of keratinocytes in mice with imiquimodmediated psoriasis and inhibits differentiation of TH17 cells through the JAK3/STAT3 axis

2020 ◽  
Author(s):  
Quan Shi ◽  
Qi He ◽  
Weiming Chen ◽  
Jianwen Long ◽  
Bo Zhang
Keyword(s):  
T Cells ◽  
In Silico ◽  
Th17 Cells ◽  
Skin Lesions ◽  
Docking Studies ◽  
Inflammatory Disorder ◽  
T Helper 17 ◽  
In Silico Docking

IntroductionOleuropein (OLP) is polyphenol obtained from olive oil; it is proved in Chinese traditional medicine for its use in disorders including autoimmune and inflammatory disorders. Psoriasis (PSR) is an autoimmune and inflammatory disorder triggered by T-helper-17 (Th17) cells.Material and methodsWe developed an imiquimod (IMQ)-mediated PSR model in mice to study the anti-inflammatory role of OLP in psoriasis. The mice were given 50 mg/kg and 100 mg/kg dose of OLP. Histology was done to assess the inflammation of lesions. Western blot analysis was done for JAK3/STAT3 in isolated T cells, expression of RORgt was done by RT-PCR. The In silico molecular docking studies were done for interaction of OLP with target protein STAT3 and JAK3.ResultsTreatment of OLP attenuated proliferation in IMQ-mediated keratinocytes, improved infiltration of CD3+ cells in the skin lesions and in CD4+ and CD8+ T cells and also ameliorated the levels of cytokines. In in vitro studies in isolated T cells, OLP blocked the differentiation of Th17 cells and also the levels of IL-17 and the JAK3/STAT3 pathway. The in silico docking showed that OLP had potential binding affinity with JAK3 and STAT3 which was parallel to in vivo and in vitro findings.ConclusionsOLP ameliorates psoriasis skin lesions by blocking Th17-mediated inflammation. OLP may be an interesting molecule for treating autoimmunity in psoriasis.

scholarly journals Synthesis, Bioactivity, Pharmacokinetic and Biomimetic Properties of Multi-Substituted Coumarin Derivatives

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5999
Author(s):  
Annita Katopodi ◽  
Evangelia Tsotsou ◽  
Triantafylia Iliou ◽  
Georgia-Eirini Deligiannidou ◽  
Eleni Pontiki ◽  
...  
Keyword(s):  
Cell Viability ◽  
Oral Absorption ◽  
Radical Scavenging ◽  
Human Keratinocytes ◽  
Docking Studies ◽  
Hydroxyl Group ◽  
Coumarin Derivatives ◽  
In Silico Docking ◽  
A375 Cells

A series of novel multi-substituted coumarin derivatives were synthesized, spectroscopically characterized, and evaluated for their antioxidant activity, soybean lipoxygenase (LOX) inhibitory ability, their influence on cell viability in immortalized human keratinocytes (HaCaT), and cytotoxicity in adenocarcinomic human alveolar basal epithelial cells (A549) and human melanoma (A375) cells, in vitro. Coumarin analogues 4a–4f, bearing a hydroxyl group at position 5 of the coumarin scaffold and halogen substituents at the 3-phenyl ring, were the most promising ABTS•+ scavengers. 6,8-Dibromo-3-(4-hydroxyphenyl)-4-methyl-chromen-2-one (4k) and 6-bromo-3-(4,5-diacetyloxyphenyl)-4-methyl-chromen-2-one (3m) exhibited significant lipid peroxidation inhibitory activity (IC50 36.9 and 37.1 μM). In the DCF-DA assay, the 4′-fluoro-substituted compound 3f (100%), and the 6-bromo substituted compounds 3i (80.9%) and 4i (100%) presented the highest activity. The 3′-fluoro-substituted coumarins 3e and 4e, along with 3-(4-acetyloxyphenyl)-6,8-dibromo-4-methyl-chromen-2-one (3k), were the most potent lipoxygenase (LOX) inhibitors (IC50 11.4, 4.1, and 8.7 μM, respectively) while displaying remarkable hydroxyl radical scavenging ability, 85.2%, 100%, and 92.9%, respectively. in silico docking studies of compounds 4e and 3k, revealed that they present allosteric interactions with the enzyme. The majority of the analogues (100 μΜ) did not affect the cell viability of HaCaT cells, though several compounds presented over 60% cytotoxicity in A549 or A375 cells. Finally, the human oral absorption (%HOA) and plasma protein binding (%PPB) properties of the synthesized coumarins were also estimated using biomimetic chromatography, and all compounds presented high %HOA (>99%) and %PPB (60–97%) values.

scholarly journals Antioxidant and Hypoglycemic Properties of Seeds of Cucurbitaceae Family from Western Nepal

2019 ◽  
Vol 9 (2) ◽  
pp. 1-5
Author(s):  
Atisammodavardhana Kaundinnyayana ◽  
Anita G.C ◽  
Asmita Banstola ◽  
Kishwor Poudel ◽  
Nirmal Acharya ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Radical Scavenging ◽  
Ethanolic Extract ◽  
Positive Control ◽  
Lagenaria Siceraria ◽  
Benincasa Hispida ◽  
Ic50 Values ◽  
In Vitro Antioxidant Activity

Introduction: Diabetes mellitus is an endocrine and metabolic disorder characterized by the defect in insulin secretion or insulin action or both. The association between diabetes mellitus and oxidative stress is well established. Cucurbitaceae is the largest family containing 120 genera mostly grown for its sweet and juicy fruit in warm climates all over the world. In the present work ethanolic extracts of the seeds of Trichosanthes cucumerina Linn (Chichinno), Lagenaria siceraria (Lauka), Cucurbita pepo (Pharsi), Luffa aegiptiaca (Ghiraula), and Benincasa hispida (Kubindo) collected from Western Nepal has been evaluated for their in vitro antioxidant activity and in vivo hypoglycemic effects. Methods: In vitro antioxidant activity was assessed by using DPPH free radical scavenging activities and their IC50 values were calculated. In vivo hypoglycemic effect was examined on normoglycemic rats. The clinical significance of ethanolic extract at the doses of 250 and 500 mg/kg body weight was investigated in 0, 30, 60, 120 and 180 minutes of oral administration. Metformin treated group was used as the positive control. Results: For DPPH radical scavenging action, the IC50 values of Trichosanthes cucumerina, Luffa aegiptiaca, Benincasa  hispida, Cucurbita pepo, Lagenaria siceraria were found to be 60.72, 127.73, 49.63, 98.16 and 52.46 µg/ml respectively which were compared to the IC50 value of ascorbic acid (Positive control) which was found to be 38.11 µg/ml. The extracts of Benincasa hispida, and were having higher antioxidant activity and tested for in vivo hypoglycemic activity.In vivo administration of two doses of ethanolic extract of Lagenaria siceraria reduced the level of blood glucose while the best result was obtained at 250 mg/kg. Conclusions: Present study revealed promising antioxidant and hypoglycemic activity of ethanolic extract of Lagenaria siceraria. The further exploration of Lagenaria siceraria for its effective use in the traditional medicinal system is essential.

scholarly journals Therapeutic Effects of Atranorin towards the Proliferation of Babesia and Theileria Parasites

Pathogens ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 127 ◽  
Author(s):  
Amany Magdy Beshbishy ◽  
Gaber El-Saber Batiha ◽  
Luay Alkazmi ◽  
Eman Nadwa ◽  
Eman Rashwan ◽  
...  
Keyword(s):  
Mouse Embryonic Fibroblast ◽  
Drug Candidate ◽  
Therapeutic Effects ◽  
Diminazene Aceturate ◽  
Human Foreskin Fibroblasts ◽  
Ic50 Values ◽  
Nih 3T3 ◽  
Embryonic Fibroblast

Atranorin (ATR), is a compound with multidirectional biological activity under different in vitro and in vivo conditions and it is effective as an antibacterial, antiviral, antiprotozoal and anti-inflammatory agent. In the current study, the in vitro as well as in vivo chemotherapeutic effect of ATR as well as its combined efficacy with the existing antibabesial drugs (diminazene aceturate (DA), atovaquone (AV) and clofazimine (CF)) were investigated on six species of piroplasm parasites. ATR suppressed B. bovis, B. bigemina, B. divergens, B. caballi and T. equi multiplication in vitro with IC50 values of 98.4 ± 4.2, 64.5 ± 3.9, 45.2 ± 5.9, 46.6 ± 2.5, and 71.3 ± 2.7 µM, respectively. The CCK test was used to examine ATR’s cytotoxicity and adverse effects on different animal and human cell lines, the main hosts of piroplasm parasites and it showed that ATR affected human foreskin fibroblasts (HFF), mouse embryonic fibroblast (NIH/3T3) and Madin-Darby Bovine Kidney (MDBK) cell viability in a dose-related effect with a moderate selective index. The combined efficacy of ATR with DA, CF, and AV exhibited a synergistic and additive efficacy toward all tested species. In the in vivo experiment, ATR prohibited B. microti multiplication in mice by 68.17%. The ATR-DA and ATR-AV combination chemotherapies were more potent than ATR monotherapy. These results indicate the prospects of ATR as a drug candidate for piroplasmosis treatment.

scholarly journals Design and Synthesis of Novel Thiazolo[5,4-d]Pyrimidine Derivatives with High Affinity for Both the Adenosine A1 and A2A Receptors, and Efficacy in Animal Models of Depression

2021 ◽  
Vol 14 (7) ◽  
pp. 657
Author(s):  
Flavia Varano ◽  
Daniela Catarzi ◽  
Erica Vigiani ◽  
Diego Dal Ben ◽  
Michela Buccioni ◽  
...  
Keyword(s):  
Preference Test ◽  
Tail Suspension Test ◽  
Docking Studies ◽  
In Vivo Studies ◽  
A2a Receptors ◽  
Design And Synthesis ◽  
Sucrose Preference Test ◽  
New Compounds

New compounds with a 7-amino-2-arylmethyl-thiazolo[5,4-d]pyrimidine structure were synthesized and evaluated in vitro for their affinity and/or potency at the human (h) A1, hA2A, hA2B, and hA3 adenosine receptors (ARs). Several compounds (5, 8–10, 13, 18–19) were characterized by nanomolar and subnanomolar binding affinities for the hA1 and the hA2A AR, respectively. Results of molecular docking studies supported the in vitro results. The 2-(2-fluorobenzyl)-5-(furan-2yl)-thiazolo[5,4-d]pyrimidin-7-amine derivative 18 (hA1 Ki = 1.9 nM; hA2A Ki = 0.06 nM) was evaluated for its antidepressant-like activity in in vivo studies, the forced swimming test (FST), the tail suspension test (TST), and the sucrose preference test (SPT) in mice, showing an effect comparable to that of the reference amitriptyline.

scholarly journals Bupleurum chinense Roots: a Bioactivity-Guided Approach toward Saponin-Type NF-κB Inhibitors

Planta Medica ◽  
2017 ◽  
Vol 83 (14/15) ◽  
pp. 1242-1250 ◽  
Author(s):  
Xin Liu ◽  
Simone Latkolik ◽  
Atanas Atanasov ◽  
Olaf Kunert ◽  
Eva-Maria Pferschy-Wenzig ◽  
...  
Keyword(s):  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Gene Model ◽  
Synthetic Compound ◽  
Ic50 Values ◽  
A Cell ◽  
Radix Bupleuri ◽  
New Compounds ◽  
First Time

AbstractThe roots of Bupleurum chinense have a long history in traditional medicine to treat infectious diseases and inflammatory disorders. Two major compounds, saikosaponins A and D, were reported to exert potent anti-inflammatory activity by inhibiting NF-κB. In the present study, we isolated new saikosaponin analogues from the roots of B. chinese interfering with NF-κB activity in vitro. The methanol-soluble fraction of the dichloromethane extract of Radix Bupleuri was subjected to activity-guided isolation yielding 18 compounds, including triterpenoids and polyacetylenes. Their structures were determined by spectroscopic methods as saikogenin D (1), prosaikogenin D (2), saikosaponins B2 (3), W (4), B1 (5), Y (6), D (7), A (8), E (9), B4 (10), B3 (11), and T (12), saikodiyne A (13), D (14), E (15) and F (16), falcarindiol (17), and 1-linoleoyl-sn-glycero-3-phosphorylcholine (18). Among them, 4, 15, and 16 are new compounds, whereas 6, previously described as a semi-synthetic compound, is isolated from a natural source for the first time, and 13–17 are the first reports of polyacetylenes from this plant. Nine saponins/triterpenoids were tested for inhibition of NF-κB signaling in a cell-based NF-κB-dependent luciferase reporter gene model in vitro. Five of them (1, 2, 4, 6, and 8) showed strong (> 50%, at 30 µM) NF-κB inhibition, but also varying degrees of cytotoxicity, with compounds 1 and 4 (showing no significant cytotoxicity) presenting IC50 values of 14.0 µM and 14.1 µM in the cell-based assay, respectively.

scholarly journals In Vitro Antioxidant Capacity of Opuntia spp. Fruits Measured by the LOX-FL Method and its High Sensitivity Towards Betalains

2021 ◽  
Author(s):  
Andrea Gómez-Maqueo ◽  
Mario Soccio ◽  
M. Pilar Cano
Keyword(s):  
Antioxidant Activity ◽  
Ascorbic Acid ◽  
Antioxidant Capacity ◽  
Radical Scavenging ◽  
High Sensitivity ◽  
Biological Mechanisms ◽  
First Time ◽  
Opuntia Spp

AbstractCurrent in vitro methodologies neglect or subestimate the contribution of betalains to antioxidant capacity in foods because they do not reflect their in vivo biological mechanisms. In this study, we assessed the sensibility of the lipoxygenase-fluorescein (LOX-FL) method towards betalains, phenolic compounds and ascorbic acid from Opuntia spp. fruits; and (ii) the antioxidant capacity of peel and pulp extracts from Opuntia ficus-indica L. Mill (var. Fresa, Colorada and Blanco) and Opuntia stricta var. Dillenii; by comparing the LOX-FL method to traditional antioxidant methods (ORAC and TEAC). The spectrophotometric monitoring of the LOX-FL reaction avoided interference caused by betalain pigments. Indicaxanthin and betanin showed high antiperoxidative and radical scavenging mechanisms in the LOX-FL assay. O. stricta var. Dillenii tissues the highest antioxidant capacity which correlated with betanin content. ORAC and TEAC antioxidant methods were less sensible towards betalain antioxidant activity. To our knowledge, this is the first time the LOX-FL antioxidant method has been used on betalains and betalain-rich foods. Graphical Abstract

In silico Exploration of Bioactive Phytochemicals Against Neurodegenerative Diseases Via Inhibition of Cholinesterases

2020 ◽  
Vol 26 (33) ◽  
pp. 4151-4162 ◽  
Author(s):  
Fawzi Mahomoodally ◽  
Hassan H. Abdallah ◽  
Shanoo Suroowan ◽  
Sharmeen Jugreet ◽  
Yansheng Zhang ◽  
...  
Keyword(s):  
Neurodegenerative Disorders ◽  
In Silico ◽  
Randomized Clinical Trials ◽  
Synaptic Cleft ◽  
Docking Studies ◽  
In Vivo Studies ◽  
In Silico Docking ◽  
Long Term Treatment

Neurodegenerative disorders are estimated to become the second leading cause of death worldwide by 2040. Despite the widespread use of diverse allopathic drugs, these brain-associated disorders can only be partially addressed and long term treatment is often linked with dependency and other unwanted side effects. Nature, believed to be an arsenal of remedies for any illness, presents an interesting avenue for the development of novel neuroprotective agents. Interestingly, inhibition of cholinesterases, involved in the breakdown of acetylcholine in the synaptic cleft, has been proposed to be neuroprotective. This review therefore aims to provide additional insight via docking studies of previously studied compounds that have shown potent activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in vitro. Indeed, the determination of potent plant-based ligands for this purpose through in silico methods enables the elimination of lengthy and costly traditional methods of drug discovery. Herein, a literature search was conducted to identify active phytochemicals which are cholinesterase inhibitors. Following which in silico docking methods were applied to obtain docking scores. Compound structures were extracted from online ZINC database and optimized using AM1 implemented in gaussian09 software. Noteworthy ligands against AChE highlighted in this study include: 19,20-dihydroervahanine A and 19, 20-dihydrotabernamine. Regarding BChE inhibition, the best ligands were found to be 8-Clavandurylkaempferol, Na-methylepipachysamine D; ebeiedinone; and dictyophlebine. Thus, ligand optimization between such phytochemicals and cholinesterases coupled with in vitro, in vivo studies and randomized clinical trials can lead to the development of novel drugs against neurodegenerative disorders.

Indane-1,3-diones: as potential and selective α-glucosidase inhibitors, their synthesis, in vitro and in silico studies.

2020 ◽  
Vol 16 ◽  
Author(s):  
Asma Mukhtar ◽  
Shazia Shah ◽  
Kanwal ◽  
Shehryar Hameed ◽  
Khalid Mohammed Khan ◽  
...  
Keyword(s):  
In Silico ◽  
Binding Mode ◽  
Docking Studies ◽  
Moderate Activity ◽  
Spectroscopic Techniques ◽  
In Silico Docking ◽  
In Silico Studies ◽  
Synthetic Molecules ◽  
Ic50 Values

Background: Diabetes mellitus is one the most chronic metabolic disorder. Since past few years our research group had synthesized and evaluated libraries of heterocyclic compounds against α and β-glucosidase enzymes and found encouraging results. The current study comprises of evaluation of indane-1,3-dione as antidiabetic agents based on our previously reported results obtained from closely related moiety isatin and its derivatives. Objective: A library of twenty three indane-1,3-dione derivatives (1-23) was synthesized and evaluated for α and βglucosidase inhibitions. Moreover, in silico docking studies were carried out to investigate the putative binding mode of selected compounds with the target enzyme. Method: The indane-1,3-dione derivatives (1-23) were synthesized by Knoevenagel condensation of different substituted benzaldehydes with indane-1,3-dione under basic condition. The structures of synthetic molecules were deduced by using different spectroscopic techniques including 1H-, 13C-NMR, EI-MS, and CHN analysis. Compounds (1-23) were evaluated for α and β-glucosidase inhibitions by adopting the literature protocols. Result: Off twenty three, eleven compounds displayed good to moderate activity against α-glucosidase enzyme, nonetheless, all compounds exhibited less than 50% inhibition against β-glucosidase enzyme. Compounds 1, 14, and 23 displayed good activity against α-glucosidase enzyme with IC50 values of 2.80 ± 0.11, 0.76 ± 0.01, and 2.17 ± 0.18 µM, respectively. The results have shown that these compounds have selectively inhibited the α-glucosidase enzyme. The in silico docking studies also supported the above results and showed different types of interactions of synthetic molecules with the active site of enzyme. Conclusion: The compounds 1, 14, and 23 have shown good inhibition against α-glucosidase and may potentially serve as lead for the development of new therapeutic representatives.

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