Synthesis, Molecular Docking, Druglikeness Analysis, and ADMET Prediction of the Chlorinated Ethanoanthracene Derivatives as Possible Antidepressant Agents

Sultan, Mujeeb A.; Galil, Mansour S. A.; Al-Qubati, Mohyeddine; Omar, Mufeed M.; Barakat, Assem

doi:10.3390/app10217727

Cited by 15 publications

(12 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Analysis of the pharmacokinetics and drug-likeness features such as molecular weight (< 500 g/mol), number of hydrogen bond donor (not > 5), number of H-bond acceptor (< 10), bioavailability (> 10%), and octanol-water partition coefficient log P (not >5) showed that orientin had two violations exceeding the acceptable limit in the number of H-bond donor (8) and acceptor (11) while ursolic acid has one violation (Table 4). Druglikeness is a measure of similarity between certain compound and standard drug as evaluated based on molecular properties (such as hydrogen bonding, hydrophobicity, ) and structural merits [60,61]. A vital index at predicting the worthiness of a compound as a drug candidate is Lipinski rule of five, which basically indicates that a compound will possibly exhibit poor bioavailability if it violates the five rules [62].…”

Section: Pharmacokinetics Investigationmentioning

confidence: 99%

Identification of Flavonoid C-Glycosides as Promising Antidiabetics Targeting Protein Tyrosine Phosphatase 1B

Rampadarath

Balogun

Pillay

et al. 2022

Journal of Diabetes Research

View full text Add to dashboard Cite

Protein tyrosine phosphatase 1B (PTP1B), a negative regulator of the insulin signaling pathway, has gained attention as a validated druggable target in the management of type 2 diabetes mellitus (T2DM). The lack of clinically approved PTP1B inhibitors has continued to prompt research in plant-derived therapeutics possibly due to their relatively lesser toxicity profiles. Flavonoid C-glycosides are one of the plant-derived metabolites gaining increased relevance as antidiabetic agents, but their possible mechanism of action remains largely unknown. This study investigates the antidiabetic potential of flavonoid C-glycosides against PTP1B in silico and in vitro. Of the seven flavonoid C-glycosides docked against the enzyme, three compounds (apigenin, vitexin, and orientin) had the best affinity for the enzyme with a binding score of –7.3 kcal/mol each, relative to –7.4 kcal/mol for the reference standard, ursolic acid. A further probe (in terms of stability, flexibility, and compactness) of the complexes over a molecular dynamics time study of 100 ns for the three compounds suggested orientin as the most outstanding inhibitor of PTP1B owing to its overall -34.47 kcal/mol binding energy score compared to ursolic acid (-19.24 kcal/mol). This observation was in accordance with the in vitro evaluation result, where orientin had a half maximal inhibitory concentration (IC50) of 0.18 mg/ml relative to 0.13 mg/ml for the reference standard. The kinetics of inhibition of PTP1B by orientin was mixed-type with V max and K m values of 0.004 μM/s and 0.515 μM. Put together, the results suggest orientin as a potential PTP1B inhibitor and could therefore be further explored in the management T2DM as a promising therapeutic agent.

show abstract

Section: Pharmacokinetics Investigationmentioning

confidence: 99%

Identification of Flavonoid C-Glycosides as Promising Antidiabetics Targeting Protein Tyrosine Phosphatase 1B

Rampadarath

Balogun

Pillay

et al. 2022

Journal of Diabetes Research

View full text Add to dashboard Cite

show abstract

“…Many drug candidates fail due to their high cytotoxicity. [25,26] Therefore we evaluated the toxicity risks of all compounds by using Osiris property explorer (Table S3). Especially compounds 2m, 2g, 2k, 3e and 3l showed no toxicity regarding mutagenicity, tumorigenicity, irritant effect and effect on the reproductive system (Table 4).…”

Section: In Silico Admet Propertiesmentioning

confidence: 99%

Synthesis, Biological Evaluation and in Silico Studies of New Pyrazoline Derivatives Bearing Benzo[d]thiazol‐2(3H)‐one Moiety as Potential Urease Inhibitors

Tok

Baltaş

Tatar

et al. 2022

Chemistry & Biodiversity

View full text Add to dashboard Cite

Novel pyrazoline derivatives containing benzo [d]thiazol-2(3H)-one moiety were synthesized and screened for their inhibitory properties against urease, a clinically important metabolic enzyme. In vitro enzyme inhibition studies revealed that all pyrazolines (7.21-87.77 μM) were more potent than the standard inhibitor acetohydroxamic acid (251.74 μM) against the urease enzyme. Most notably, compound 2m, which is more active than the other compounds in vitro and molecular docking studies, showed a significant inhibition potential and efficient IC 50 values (7.21 � 0.09 μM) and in silico inhibition constant (0.11 μM). Furthermore, molecular dynamics (MD) simulation analysis suggests that the binding stability of urease enzyme and compound 2m were stably maintained during the 100 ns simulation time. Compound 2m also exhibited good physicochemical and pharmacokinetic parameters. The overall results of urease inhibition have indicated that these pyrazoline derivative compounds can be further optimized and developed for the discovery of novel urease inhibitors.

show abstract

“…Then, a ligand toxicity test was carried out using Data Warrior software. Several studies have used this software to find new medicinal compounds, such as cancer and antidepressant drugs [37][38]. The results of the predictive analysis of ligand toxicity using Data Warrior are shown in Table 5 [39].…”

Section: Prediction Of Ligand Toxicitymentioning

confidence: 99%

Potential <i>Adenostemma lavenia</i> and <i>Muntingia calabura</i> Extracts to Inhibit Cyclooxygenase-2 Activity as a Therapeutic Strategy for Anti-inflammation: Experimental and Theoretical Studies

2022

View full text Add to dashboard Cite

Continuous inflammation can cause new and more severe diseases, thus effective treatments are needed. One of the common inflammation treatments is given by reducing prostaglandins' production through the inhibition of COX-2 activity. This experiment aims to examine the potential application of plant extracts of Adenostemma lavenia and Muntingia calabura (Jamaica cherry) as anti-inflammatory agents in inhibiting COX-2 activity through in silico and in vitro assays. Molecular docking and molecular dynamics simulation were accomplished to evaluate the stability of the complex between COX-2 and ligands. The COX-2 inhibition was determined using the COX-2 Inhibitor Screening Assay KIT. Based on the docking results, the active compound from A. lavenia, ligand 1a,9b-dihydro-1H-cyclopropa[a]anthracene, has the lowest binding energy of -8.7 kcal/mol. In comparison, M. calabura contains 7-hydroxyflavone ligand with a Gibbs free energy of -9.1 kcal/mol. The molecular dynamics study demonstrates that COX-2 maintains its stability when forming interactions with selected compounds from all the tested extracts. The results of the COX-2 inhibition test showed that 96% EtOH extract of A. Lavenia at concentrations of 25 and 100 ppm had an inhibitory activity of 98%; meanwhile, 70% and 96% EtOH extracts of M. calabura at 1000 ppm concentration could inhibit COX-2 activity up to 100%. The results demonstrate that both plants show potential anti-inflammatory activity.

show abstract

Synthesis, Molecular Docking, Druglikeness Analysis, and ADMET Prediction of the Chlorinated Ethanoanthracene Derivatives as Possible Antidepressant Agents

Cited by 15 publications

References 76 publications

Identification of Flavonoid C-Glycosides as Promising Antidiabetics Targeting Protein Tyrosine Phosphatase 1B

Identification of Flavonoid C-Glycosides as Promising Antidiabetics Targeting Protein Tyrosine Phosphatase 1B

Synthesis, Biological Evaluation and in Silico Studies of New Pyrazoline Derivatives Bearing Benzo[d]thiazol‐2(3H)‐one Moiety as Potential Urease Inhibitors

Potential <i>Adenostemma lavenia</i> and <i>Muntingia calabura</i> Extracts to Inhibit Cyclooxygenase-2 Activity as a Therapeutic Strategy for Anti-inflammation: Experimental and Theoretical Studies

Contact Info

Product

Resources

About