scholarly journals Characterizations and Assays of α-Glucosidase Inhibition Activity on Gallic Acid Cocrystals: Can the Cocrystals be Defined as a New Chemical Entity During Binding with the α-Glucosidase?

Molecules ◽  
2020 ◽  
Vol 25 (5) ◽  
pp. 1163 ◽  
Author(s):  
Na Xue ◽  
Yutao Jia ◽  
Congwei Li ◽  
Binnan He ◽  
Caiqin Yang ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Gallic Acid ◽  
Glutaric Acid ◽  
Docking Simulation ◽  
Chemical Entity ◽  
Water Soluble ◽  
Inhibition Activity ◽  
Acid Complex ◽  
New Chemical Entity

Cocrystallization with co-former (CCF) has proved to be a powerful approach to improve the solubility and even bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs). However, it is still uncertain whether a cocrystal would exert the pharmacological activity in the form of a new chemical entity, an API-CCF supramolecule. In the present study, gallic acid (GA)-glutaric acid and GA-succinimide cocrystals were screened. The solubility, dissolution rate and oral bioavailability of the two cocrystals were evaluated. As expected, AUCs of GA-glutaric acid and GA-succinimide cocrystals were 1.86-fold and 2.60-fold higher than that of single GA, respectively. Moreover, experimental evaluations on α-glucosidase inhibition activity in vitro and theoretical simulations were used to detect whether the two cocrystals would be recognized as a new chemical entity during binding with α-glucosidase, a target protein in hypoglycemic mechanisms. The enzyme activity evaluation results showed that both GA and glutaric acid displayed α-glucosidase inhibition activity, and GA-glutaric acid cocrystals showed strengthened α-glucosidase inhibition activity at a moderate concentration, which is attributed to synergism of the two components. Molecular docking displayed that the GA-glutaric acid complex deeply entered the active cavity of the α-glucosidase in the form of a supramolecule, which made the guest-enzyme binding configuration more stable. For the GA and succinimide system, succinimide showed no enzyme inhibition activity, however, the GA-succinimide complex presented slightly higher α-glucosidase inhibition activity than that of GA. Molecular docking simulation indicated that the guest molecules entering the active cavity of the α-glucosidase were free GA and succinimide, not the GA-succinimide supramolecule.

scholarly journals In vitro comprehensive analysis of VA692 a new chemical entity for the treatment of osteoarthritis

2018 ◽  
Vol 64 ◽  
pp. 86-100 ◽  
Author(s):  
Sara Cheleschi ◽  
Valentina Calamia ◽  
Mercedes Fernandez-Moreno ◽  
Mariangela Biava ◽  
Antonio Giordani ◽  
...  
Keyword(s):  
Comprehensive Analysis ◽  
Chemical Entity ◽  
New Chemical Entity

scholarly journals Structural Basis of Binding and Rationale for the Potent Urease Inhibitory Activity of Biscoumarins

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Muhammad Arif Lodhi ◽  
Sulaiman Shams ◽  
Muhammad Iqbal Choudhary ◽  
Atif Lodhi ◽  
Zaheer Ul-Haq ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Active Sites ◽  
Docking Simulation ◽  
Cysteine Residue ◽  
Structural Basis ◽  
Bacillus Pasteurii ◽  
Nickel Ions ◽  
Jack Bean ◽  
Uv Visible

Urease belongs to a family of highly conserved urea-hydrolyzing enzymes. A common feature of these enzymes is the presence of two Lewis acid nickel ions and reactive cysteine residue in the active sites. In the current study we examined a series of biscoumarins1–10for their mechanisms of inhibition with the nickel containing active sites of Jack bean andBacillus pasteuriiureases. All these compounds competitively inhibited Jack bean urease through interaction with the nickel metallocentre, as deduced from Michaelis-Menten kinetics, UV-visible absorbance spectroscopic, and molecular docking simulation studies. Some of the compounds behaved differently in case ofBacillus pasteuriiurease. We conducted the enzyme kinetics, UV-visible spectroscopy, and molecular docking results in terms of the known protein structure of the enzyme. We also evaluated possible molecular interpretations for the site of biscoumarins binding and found that phenyl ring is the major active pharmacophore. The excellent in vitro potency and selectivity profile of the several compounds described combined with their nontoxicity against the human cells and plants suggest that these compounds may represent a viable lead series for the treatment of urease associated problems.

Design, Synthesis, Anticancer Evaluation, and Molecular Docking Studies of Novel Benzoxazole Linked 1,3,4-Oxadiazoles

2021 ◽  
Vol 21 ◽  
Author(s):  
Sushmitha Bujji ◽  
Praveen Kumar E ◽  
Sree Kanth Sivan ◽  
Manjunatha DH ◽  
Subhashini N.J.P.
Keyword(s):  
Molecular Docking ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Research Work ◽  
Docking Simulation ◽  
Research Field ◽  
Spectroscopic Techniques ◽  
Cancer Disease ◽  
Amide Derivatives

Background: Cancer disease is making a serious concern globally. Global cancer occurrence is steadily increasing every year. There is always a persistent need to develop new anticancer drugs with reduced side effects or act synergistically with the existing chemotherapeutics. Objective: Benzoxazoles are fused bicyclic nitrogen and oxygen-containing heterocyclic compounds and are considered biologically privileged scaffolds. We designed a synthetic route to link the benzoxazoles with oxadiazoles resulting in a better pharmacophore for anticancer activity. Methods: A series of novel amide derivatives of benzoxazole linked 1,3,4-oxadiazoles (10a-j) were synthesized and characterized by 1H NMR, 13C NMR, and mass spectroscopic techniques. The biological properties of the compounds were screened in vitro against four different tumor cell lines. Results: The results suggest that the compound 10b having 3,4,5-trimethoxy substitution on the phenyl ring exhibited potent anticancer activity in three cell lines (A549 = 0.13 ± 0.014 µM, MCF-7 = 0.10 ± 0.013 µM and HT-29 = 0.22 ± 0.017 µM). Notably, among the synthesized derivatives, compounds 10b, 10c, 10f, 10g, and 10i exhibited potent anticancer activity than the control IC50 in the range of 0.11 ± 0.02 to 0.93 ± 0.034 µM. Molecular docking simulation results showed compounds were stabilized by hydrogen bond and π-π interactions with the protein. Conclusion: The molecules showed comparable binding affinities with standard Combretastatin-A4. The present research work is preliminary and needs further studies to take the synthesized compounds to the next level in the cancer research field.

Molecular docking simulation and in vitro studies on estrogenic activities of flavonoids from leaves of Carya cathayensis Sarg

Steroids ◽  
2020 ◽  
Vol 163 ◽  
pp. 108726
Author(s):  
Jing-Jing Lu ◽  
Fang-Mei Zhou ◽  
Xu-Jiao Hu ◽  
Jing-Jing Fang ◽  
Cai-Xia Liu ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Simulation ◽  
In Vitro Studies ◽  
Molecular Docking Simulation ◽  
Carya Cathayensis ◽  
Carya Cathayensis Sarg

scholarly journals In-silico Molecular Docking and ADME/Pharmacokinetic Prediction Studies of Some Novel Carboxamide Derivatives as Anti-tubercular Agents

2020 ◽  
Vol 3 (4) ◽  
pp. 989-1000
Author(s):  
Mustapha Abdullahi ◽  
Shola Elijah Adeniji
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
In Silico ◽  
Density Functional ◽  
Docking Simulation ◽  
Basis Set ◽  
Hybrid Functional ◽  
Standard Drug

AbstractMolecular docking simulation of thirty-five (35) molecules of N-(2-phenoxy)ethyl imidazo[1,2-a]pyridine-3-carboxamide (IPA) with Mycobacterium tuberculosis target (DNA gyrase) was carried out so as to evaluate their theoretical binding affinities. The chemical structure of the molecules was accurately drawn using ChemDraw Ultra software, then optimized at density functional theory (DFT) using Becke’s three-parameter Lee–Yang–Parr hybrid functional (B3LYP/6-311**) basis set in a vacuum of Spartan 14 software. Subsequently, the docking operation was carried out using PyRx virtual screening software. Molecule 35 (M35) with the highest binding affinity of − 7.2 kcal/mol was selected as the lead molecule for structural modification which led to the development of four (4) newly hypothetical molecules D1, D2, D3 and D4. In addition, the D4 molecule with the highest binding affinity value of − 9.4 kcal/mol formed more H-bond interactions signifying better orientation of the ligand in the binding site compared to M35 and isoniazid standard drug. In-silico ADME and drug-likeness prediction of the molecules showed good pharmacokinetic properties having high gastrointestinal absorption, orally bioavailable, and less toxic. The outcome of the present research strengthens the relevance of these compounds as promising lead candidates for the treatment of multidrug-resistant tuberculosis which could help the medicinal chemists and pharmaceutical professionals in further designing and synthesis of more potent drug candidates. Moreover, the research also encouraged the in vivo and in vitro evaluation study for the proposed designed compounds to validate the computational findings.

scholarly journals Anticancer Activity Of Plant Genus Clerodendrum (Lamiaceae): A Review

2017 ◽  
Vol 22 (3) ◽  
pp. 182
Author(s):  
Donald Emilio Kalonio ◽  
Rini Hendriani ◽  
Elisabeth N. Barung
Keyword(s):  
Molecular Docking ◽  
Anticancer Activity ◽  
Docking Simulation ◽  
Scientific Data ◽  
Anticancer Effect ◽  
Literature Study ◽  
Molecular Docking Simulation ◽  
Chemical Content

Plants of the genus Clerodendrum (Lamiaceae) is widespread in tropical and subtropical regions. Plants of this genus are used both empirically and scientifically as anti-inflammatory, antidiabetic, antimalarial, antiviral, antihypertensive, hypolipidemic, antioxidant, and antitumor. Results of the molecular docking simulation of chemical content of these plants could potentially provide an anticancer effect. This paper aims to review the anticancer activity of plant genus Clerodendrum based on scientific data. The method used in this study is the literature study. Searches were conducted online (in the database PubMed, Science Direct and Google Scholar) and on various books (Farmakope Herbal Indonesia and PROSEA). A total 12 plants of the genus Clerodendrum have anticancer activity in vitro and in vivo, thus potentially to be developed as a source of new active compounds with anticancer activity.

Inhibitory Effect of Sesamolin on Melanogenesis in B16F10 Cells Determined by In Vitro and Molecular Docking Analyses

2020 ◽  
Vol 21 (2) ◽  
pp. 169-178
Author(s):  
Seung-Hwa Baek ◽  
Myung-Gyun Kang ◽  
Daeui Park
Keyword(s):  
Molecular Docking ◽  
Competitive Inhibition ◽  
Docking Simulation ◽  
Melanoma Cells ◽  
Inhibition Mechanism ◽  
Dual Function ◽  
Dependent Manner ◽  
Related Factors ◽  
Docking Simulations

Background: Melanin protects the skin against the harmful effects of ultraviolet irradiation. However, melanin overproduction can result in several aesthetic problems, including melasma, freckles, age spots and chloasma. Therefore, development of anti-melanogenic agents is important for the prevention of serious hyperpigmentation diseases. Sesamolin is a lignan compound isolated from sesame seeds with several beneficial properties, including potential for melanin inhibition. Objective: The aim of this study was to evaluate the anti-melanogenic effect of sesamolin in cell culture in vitro and the underlying mechanism of inhibition using molecular docking simulation. Methods: Melanogenesis was induced by 3-isobutyl-1-methylxanthine in B16F10 melanoma cells, and the inhibitory effects of sesamolin were evaluated using zymography, a tyrosinase inhibitory activity assay, western blotting, and real-time reverse transcription-polymerase chain reaction analysis. Docking simulations between sesamolin and tyrosinase were performed using Autodock vina. Results: Sesamolin significantly inhibited the expression of melanogenesis-related factors tyrosinase, and tyrosinase-related proteins 1 and 2 at the mRNA and protein levels. Treatment of melanoma cells with 50 µM sesamolin demonstrated the strongest inhibition against intercellular tyrosinase and melanin synthesis without exerting cytotoxic effects. Sesamolin significantly reduced mushroom tyrosinase activity in a dose-dependent manner via a competitive inhibition mechanism. Tyrosinase docking simulations supported that sesamolin (-6.5 kcal/mol) bound to the active site of tyrosinase more strongly than the positive control (arbutin, -5.7 kcal/mol). Conclusion: Sesamolin could be developed as a melanogenesis inhibiting agent owing to its dual function in blocking the generation of melanogenesis-related enzymes and inhibiting the enzymatic response of tyrosinase.

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