Exploring Securigera securidaca Seeds as a Source of Potential CDK1 Inhibitors: Identification of Hippeastrine and Naringenin as Promising Hit Candidates

Abdelbagi, Mohamed E. M.; Al-Mazaideh, Ghassab M.; Ahmed, Abdullah Ahmed Ali; Al‐Rimawi, Fuad; Salman, Haya Ayyal; Almutairi, Abdulrahman; Abuilaiwi, Faraj Ahmad; Wedian, Fadel

doi:10.3390/pr11051478

Cited by 6 publications

(5 citation statements)

References 87 publications

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“…Our research is unique because we have created a new formula of S. securidaca seed extract that has potential applications in various medical fields, as described in our previous publication [35]. Our findings suggest that our formulation has fewer side effects and greater efficacy compared to conventional treatments, making it a promising natural alternative.…”

Section: Analysis Of Trigonelline and Diosgenin In The Formulamentioning

confidence: 79%

Drug Formulation of Securigera securidaca Seed Extracts

et al. 2023

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S. securidaca seeds are reported to treat a variety of diseases; they contain multiple antidiabetic constituents and are widely used as anti-hyperglycemic, antibacterial, as well as anti-hyperlipidemic agents. The present work aimed to propose tablet formulations containing extracts of S. securidaca seeds in an attempt to obtain antibacterial and anti-hyperglycemic formulations with a more efficient oral hypoglycemic impact, limited side effects, and higher patient compliance for the first time, resulting in multiple benefits. Tablet formulations were created by encapsulating granules from S. securidaca seed extracts with varying concentrations of sodium starch glycolate as a super-disintegrant (0–3%). The final formulations were examined for weight variation, solubility, hardness, water content, disintegration time, friability, drug content (trigonelline and diosgenin), and in vitro drug release. The S. securidaca tablet formulations completed the weight test because the percentage deviation in the personal tablet weight and mechanical resistance from the mean were identified to be within the average range. In accordance with the results, formulations containing diosgenin as well as trigonelline as a super-disintegrant were identified as the ideal formulations. The amount of the active substance released from the tablet (S. securidaca seed extract formulation) was consistent throughout the results with the standard methods recommended by the FDA (94.05%) for diosgenin and 87.25% for trigonelline after 45 min. The acceptable limit, according to the FDA, is not more than (N.L.T.) 80% after 45 min for phase #1. The present study aimed to obtain an optimized formula for S. securidaca extract tablets that met the requirements of a good pharmaceutical preparation according to the United States Pharmacopeia (USP) and National Formulary (NF). This has important implications for the development of novel, effective treatments and significantly advances the development of natural medicine. Our findings are expected to be of interest to researchers, clinicians, and other experts in this field of study. Based on these findings, it can be inferred that the formulation of S. securidaca seed extracts with appropriate and compatible herbal dosage forms has fewer side effects and is more effective than traditional treatments.

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Section: Analysis Of Trigonelline and Diosgenin In The Formulamentioning

confidence: 79%

Drug Formulation of Securigera securidaca Seed Extracts

et al. 2023

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“…Also, the extraneous non-crucial water molecules and heteroatoms were removed by utilizing the Biovia Discovery Studio Visualizer [62], yielding a refined structure in PDB format. The YASARA web server was instrumental in adding any missing amino acids to the enzyme's structure [63][64][65]. At a pH of 7.4, the ionization states of amino acids capable of titration were calculated using the H ++ web server [66].…”

Section: Molecular Docking Preparationmentioning

confidence: 99%

Radiological and Molecular Analysis of Radioiodinated Anastrozole and Epirubicin as Innovative Radiopharmaceuticals Targeting Methylenetetrahydrofolate Dehydrogenase 2 in Solid Tumors

Binmujlli

2024

Pharmaceutics

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In the dynamic field of radiopharmaceuticals, innovating targeted agents for cancer diagnosis and therapy is crucial. Our study enriches this evolving landscape by evaluating the potential of radioiodinated anastrozole ([125I]anastrozole) and radioiodinated epirubicin ([125I]epirubicin) as targeting agents against MTHFD2-driven tumors. MTHFD2, which is pivotal in one-carbon metabolism, is notably upregulated in various cancers, presenting a novel target for radiopharmaceutical application. Through molecular docking and 200 ns molecular dynamics (MD) simulations, we assess the binding efficiency and stability of [125I]anastrozole and [125I]epirubicin with MTHFD2. Molecular docking illustrates that [125I]epirubicin has a superior binding free energy (∆Gbind) of −41.25 kJ/mol compared to −39.07 kJ/mol for [125I]anastrozole and −38.53 kJ/mol for the control ligand, suggesting that it has a higher affinity for MTHFD2. MD simulations reinforce this, showing stable binding, as evidenced by root mean square deviation (RMSD) values within a narrow range, underscoring the structural integrity of the enzyme–ligand complexes. The root mean square fluctuation (RMSF) analysis indicates consistent dynamic behavior of the MTHFD2 complex upon binding with [125I]anastrozole and [125I]epirubicin akin to the control. The radius of gyration (RG) measurements of 16.90 Å for MTHFD2-[125I]anastrozole and 16.84 Å for MTHFD2-[125I]epirubicin confirm minimal structural disruption upon binding. The hydrogen bond analysis reveals averages of two and three stable hydrogen bonds for [125I]anastrozole and [125I]epirubicin complexes, respectively, highlighting crucial stabilizing interactions. The MM-PBSA calculations further endorse the thermodynamic favorability of these interactions, with binding free energies of −48.49 ± 0.11 kJ/mol for [125I]anastrozole and −43.8 kJ/mol for MTHFD2-. The significant contribution of Van der Waals and electrostatic interactions to the binding affinities of [125I]anastrozole and [125I]epirubicin, respectively, underscores their potential efficacy for targeted tumor imaging and therapy. These computational findings lay the groundwork for the future experimental validation of [125I]anastrozole and [125I]epirubicin as MTHFD2 inhibitors, heralding a notable advancement in precision oncology tools. The data necessitate subsequent in vitro and in vivo assays to corroborate these results.

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“…The resulting structure was saved in PDB format. Any missing amino acids in the target structure were integrated using the YASARA web server tool [52][53][54]. The missing residues integrated were MET16, GLY17, SER18, SER19, HIS20, HIS21, HIS22, HIS23, HIS24, HIS25, SER26, SER27, GLY28, GLU29, ASN30, LEU31, TYR32, PHE33, GLN34, GLY35, ASP281, PRO282, VAL283, THR284, ALA285, LEU334, GLU335, GLU336, ARG337, and GLU338 [44].…”

Section: Molecular Docking and Admet Prediction 251 Protein Structure...mentioning

confidence: 99%

“…The missing residues integrated were MET16, GLY17, SER18, SER19, HIS20, HIS21, HIS22, HIS23, HIS24, HIS25, SER26, SER27, GLY28, GLU29, ASN30, LEU31, TYR32, PHE33, GLN34, GLY35, ASP281, PRO282, VAL283, THR284, ALA285, LEU334, GLU335, GLU336, ARG337, and GLU338 [44]. To determine titratable amino acid groups' ionization states at pH 7.4, the H++ web server tool was utilized [53][54][55]. Finally, AutoDock Tools v1.5.6 [56] added polar hydrogen atoms and Kollman charges to transform the output into PDBQT format.…”

Section: Molecular Docking and Admet Prediction 251 Protein Structure...mentioning

confidence: 99%

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Identification and Absorption–Distribution–Metabolism–Excretion–Toxicity Prediction of Potential MTHFD2 Enzyme Inhibitors from Urtica dioica Ethanolic Leaf Extract

Alshammari

2024

Processes

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This study aimed to explore the potential of Urtica dioica (U. dioica) ethanolic leaf extract for cancer treatment by identifying its components, evaluating its effects on cancer cell lines, and analyzing its molecular docking. The objective of this study was to investigate the anticancer properties of U. dioica ethanolic leaf extract and assess its potential as a therapeutic strategy for cancer treatment. This study utilized high-performance liquid chromatography (HPLC) to analyze the chemical composition of U. dioica ethanolic leaf extract. The anticancer effects of the extract were evaluated by assessing cell viability, determining IC50 values, and conducting ADMET analysis after oral administration. U. dioica ethanolic leaf extract was found to contain methyl hexadecanoate as its primary component, along with flavonoids and polyphenols. It effectively reduced cell viability in various tested cancer cell lines, with IC50 values varying for each cell line. The duration of treatment significantly influenced cell viability, with the most significant reduction observed after 48 h. Molecular docking studies suggested that catechin, kaempferol, and quercetin-3-O-rutinoside may have potential as inhibitors of the MTHFD2 enzyme. This study revealed the potential of U. dioica and its compounds in cancer treatment. Ethanolic leaf extract has been shown to have anticancer effects on various cancer cell lines, with catechin and kaempferol showing promise as inhibitors of the MTHFD2 enzyme. Further research is warranted to explore the therapeutic implications of U. dioica in cancer treatment.

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Exploring Securigera securidaca Seeds as a Source of Potential CDK1 Inhibitors: Identification of Hippeastrine and Naringenin as Promising Hit Candidates

Cited by 6 publications

References 87 publications

Drug Formulation of Securigera securidaca Seed Extracts

Drug Formulation of Securigera securidaca Seed Extracts

Radiological and Molecular Analysis of Radioiodinated Anastrozole and Epirubicin as Innovative Radiopharmaceuticals Targeting Methylenetetrahydrofolate Dehydrogenase 2 in Solid Tumors

Identification and Absorption–Distribution–Metabolism–Excretion–Toxicity Prediction of Potential MTHFD2 Enzyme Inhibitors from Urtica dioica Ethanolic Leaf Extract

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