scholarly journals Isolation, characterization, anticancer and antioxidant activities of 2-methoxy mucic acid from Rhizophora apiculata: An in vitro and in silico studies

2021 ◽  
Author(s):  
A. Parthiban ◽  
Sachithanandam V ◽  
P. Lalitha ◽  
Jayaraman Muthukumaran ◽  
Monika Jain ◽  
...  
Keyword(s):  
In Silico ◽  
Antioxidant Activities ◽  
Antioxidant Property ◽  
Dynamics Simulation ◽  
Mucic Acid ◽  
Rhizophora Apiculata ◽  
In Silico Studies ◽  
Ft Ir ◽  
First Time

Abstract In this present study, the sugar based bioactive molecule, 2-methoxy mucic acid ( 4) was isolated for the first time from the methanolic extract from the leaves of Rhizophora apiculata . The structure of compound was well characterized by different spectroscopic analysis, including FT-IR, 1 H, 13 C NMR spectroscopy and HRMS. Anticancer activity of 2-methoxy mucic acid ( 4 ) was evaluated against HeLa and MDA-MB231 cancer cell lines and they displayed promising activity with the IC 50 values of 22.88283±0.72 µg/ml in HeLa and 2.91925±0.52 µg/ml in case of MDA-MB231, respectively. The antioxidant property of 2-methoxy mucic acid ( 4 ) was found to be (IC 50 ) 21.361±0.41 µg/ml. Apart from in vitro studies, we also performed extensive in silico studies (molecular docking and molecular dynamics simulation) on four key anti-apoptotic Bcl-2 family members (Bcl-2, Bcl-w, Bcl-xL and Bcl-B) towards 2-methoxy mucic acid ( 4) and the results revealed that this molecule showed higher binding affinity towards Bcl-B protein ( ΔG = -5.8 kcal/mol) and the structural stability of Bcl-B protein was significantly improved upon binding of this molecule. The present study affords key insights about the importance of 2-methoxy mucic acid ( 4 ), and thus leads to open the therapeutic route for anticancer drug discovery process.

Discovery of Natural Product Inspired 3-Phenyl-1H-isochromen-1-ones as Highly Potent Antioxidant and Antiplatelet Agents: Design, Synthesis, Biological Evaluation, SAR and in silico Studies

2021 ◽  
Vol 27 ◽  
Author(s):  
Bharti Rajesh Kumar Shyamlal ◽  
Manas Mathur ◽  
Dharmendra K. Yadav ◽  
Irina V. Mashevskaya ◽  
Mohamed El-Shazly ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
In Silico ◽  
Antioxidant Activities ◽  
In Silico Analysis ◽  
Antiplatelet Agents ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
In Silico Studies

Background: Several natural/synthetic molecules having structure similar to 1H-isochromen-1-ones have been reported to display promising antioxidants and platelet aggregation inhibitory activity. Isocoumarin (1H-2-benzopyran-1-one) skeleton, either whole or as a part of molecular framework, have been explored for their antioxidant or antiplatelet activities. Introduction: Based on literature, a new prototype i.e., 3-phenyl-1H-isochromen-1-ones based compounds have been rationalized to possess both antioxidant as well as antiplatelet activities. Consequently, no reports are available regarding its inhibition either by cyclooxygenase-1 (COX-1) enzyme or by arachidonic acid (AA)-induced platelet aggregation. This prompted us to investigate 3-phenyl-1H-isochromen-1-ones towards antioxidant and antiplatelet agents. Methods: The goal of this work to identify new 3-phenyl-1H-isochromen-1-ones based compounds via synthesis of a series of analogues and performing in vitro antioxidant as well as AA-induced antiplatelet activities and then, identification of potent compounds by SAR and molecular docking studies. Results: Out of all synthesized 3-phenyl-1H-isochromen-1-ones analogues, five compounds showed 7-folds to 16-folds highly potent antioxidant activities than ascorbic acid. Altogether, ten 3-phenyl-1H-isochromen-1-one analogues displayed antioxidant activities in 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Almost, all the 3-phenyl-1H-isochromen-1-one analogues exhibited potent AA-induced antiplatelet activity; few of them displayed 7-folds more activity as compared to aspirin. Further, in silico analysis validated the wet results. Conclusion: We disclose the first detailed study for the identification of 3-phenyl-1H-isochromen-1-one analogues as highly potent antioxidant as well as antiplatelet agents. The article describes the scaffold designing, synthesis, bioevaluation, structure-activity relationship and in silico studies of pharmaceutically privileged bioactive 3-phenyl-1H-isochromen-1-one class of heterocycles.

scholarly journals Triterpenic Acids as Non-Competitive α-Glucosidase Inhibitors from Boswellia elongata with Structure-Activity Relationship: In Vitro and In Silico Studies

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 751 ◽  
Author(s):  
Najeeb Ur Rehman ◽  
Sobia Ahsan Halim ◽  
Mohammed Al-Azri ◽  
Majid Khan ◽  
Ajmal Khan ◽  
...  
Keyword(s):  
In Silico ◽  
Dissociation Constants ◽  
Docking Study ◽  
Spectroscopic Techniques ◽  
Significant Activity ◽  
Active Compounds ◽  
In Silico Docking ◽  
In Silico Studies ◽  
First Time

Fourteen triterpene acids, viz., three tirucallane-type (1–3), eight ursane-type (4–11), two oleanane-type (12, 13) and one lupane type (21), along with boswellic aldehyde (14), α-amyrine (15), epi-amyrine (16), straight chain acid (17), sesquiterpene (19) and two cembrane-type diterpenes (18, 20) were isolated, first time, from the methanol extract of Boswellia elongata resin. Compound (1) was isolated for first time as a natural product, while the remaining compounds (2‒21) were reported for first time from B. elongata. The structures of all compounds were confirmed by advanced spectroscopic techniques including mass spectrometry and also by comparison with the reported literature. Eight compounds (1–5, 11, 19 and 20) were further screened for in vitro α-glucosidase inhibitory activity. Compounds 3–5 and 11 showed significant activity against α-glucosidase with IC50 values ranging from 9.9–56.8 μM. Compound 4 (IC50 = 9.9 ± 0.48 μM) demonstrated higher inhibition followed by 11 (IC50 = 14.9 ± 1.31 μM), 5 (IC50 = 20.9 ± 0.05 μM) and 3 (IC50 = 56.8 ± 1.30 μM), indicating that carboxylic acid play a key role in α-glucosidase inhibition. Kinetics studies on the active compounds 3–5 and 11 were carried out to investigate their mechanism (mode of inhibition and dissociation constants Ki). All compounds were found to be non-competitive inhibitors with Ki values in the range of 7.05 ± 0.17–51.15 ± 0.25 µM. Moreover, in silico docking was performed to search the allosteric hotspot for ligand binding which is targeted by our active compounds investigates the binding mode of active compounds and it was identified that compounds preferentially bind in the allosteric binding sites of α-glucosidase. The results obtained from docking study suggested that the carboxylic group is responsible for their biologic activities. Furthermore, the α-glucosidase inhibitory potential of the active compounds is reported here for the first time.

Exploring the Molecular Mechanisms of 17β-HSD5-induced Carcinogenicity of Catha Edulis via Molecular Modeling Approach.

2020 ◽  
Vol 16 ◽  
Author(s):  
Maria Saeed ◽  
Sajda Ashraf ◽  
Rashad Alsanosi ◽  
Hassan A. Alhazmi ◽  
Mohammed AlBratty ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
In Silico ◽  
Molecular Mechanisms ◽  
Dynamics Simulation ◽  
Catha Edulis ◽  
Khat Chewing ◽  
First Time

Background: The tradition of khat chewing has been deep-rooted in the African and Arabian Peninsula for centuries. Due to its amphetamine-like psycho-stimulant or euphoric effect, Khat has been used by millions in Somalia, Ethiopia, Saudi Arabia and Yemen. The long-term use of Khat can induce tremendous health outcomes, which may be serious and irreversible. Objective: Prolong use of Khat constituents has been associated with different types of cancers such as prostatic, breast and ovarian cancer. However, it has been very difficult to identify the molecular targets involved in Khat carcinogenesis that interact with the Khat constituents by in vitro/in vivo experimental tools. Method: In silico tools to predict potential targets involved in the carcinogenesis of Khat. Pass on-line prediction server was used for the prediction of a potential molecular target for Khat constituents. Molecular Dynamics simulation and MMGBSA calculation of the predicted target. Results: Molecular Dynamics simulation and MM-GBSA calculation. Results revealed that among Khat constituents βSitosterol showed high binding affinity towards 17β-HSD5. On the other hand, this study highlights for the first time, some new interactions, which were observed in the case of cathine, cathinone and nerol during the simulation. Conclusion: In silico molecular dynamic simulation tools were used for the first time to investigate the molecular mechanism of widely used leaves of psychoactive Khat (Catha edulis) constituent, which is used extensively all over the world. The present study provides deep insight to understand the effect of Khat constituents involve in the impairment of reproductive system and its binding to 17β-HSD5. ADMET profiling also suggested that few Khat constituents do not fulfill the requirements of Lipinski rule of five i.e. poor absorption and blood-brain barrier impermeability.

scholarly journals Synthesis, Antimicrobial, Anticancer, PASS, Molecular Docking, Molecular Dynamic Simulations and Pharmacokinetic Predictions of Some Methyl β-d-Galactopyranoside Analogs

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 7016
Author(s):  
Md. Ruhul Amin ◽  
Farhana Yasmin ◽  
Mohammed Anowar Hosen ◽  
Sujan Dey ◽  
Shafi Mahmud ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Density Functional ◽  
Dynamics Simulation ◽  
Dynamic Simulations ◽  
Stable Conformation ◽  
Chemical Structures ◽  
In Silico Admet ◽  
In Silico Studies

A series of methyl β-D-galactopyranoside (MGP, 1) analogs were selectively acylated with cinnamoyl chloride in anhydrous N,N-dimethylformamide/triethylamine to yield 6-O-substitution products, which were subsequently converted into 2,3,4-tri-O-acyl analogs with different acyl halides. Analysis of the physicochemical, elemental, and spectroscopic data of these analogs revealed their chemical structures. In vitro antimicrobial testing against five bacteria and two fungi and the prediction of activity spectra for substances (PASS) showed promising antifungal functionality comparing to their antibacterial activities. Minimum inhibition concentration (MIC) and minimum bactericidal concentration (MBC) tests were conducted for four compounds (4, 5, 6, and 9) based on their activity. MTT assay showed low antiproliferative activity of compound 9 against Ehrlich’s ascites carcinoma (EAC) cells with an IC50 value of 2961.06 µg/mL. Density functional theory (DFT) was used to calculate the thermodynamic and physicochemical properties, whereas molecular docking identified potential inhibitors of the SARS-CoV-2 main protease (6Y84). A 150-ns molecular dynamics simulation study revealed the stable conformation and binding patterns in a stimulating environment. In silico ADMET study suggested all the designed molecules to be noncarcinogenic, with low aquatic and nonaquatic toxicity. In summary, all of these antimicrobial, anticancer and in silico studies revealed that newly synthesized MGP analogs possess promising antiviral activity, to serve as a therapeutic target for COVID-19.

scholarly journals In vitro Antioxidant and Anticholinesterase Activities of Ouratea fieldingiana (Gardner) Eng. Leaf Extract and Correlation with Its Phenolics Profile with an in silico Study in Relation to Alzheimer’s Disease

2022 ◽  
Author(s):  
Lucas Frota ◽  
Daniela Alves ◽  
Leonardo Freitas ◽  
Francisco Lopes ◽  
Marcia Marinho ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
In Silico ◽  
Antioxidant Activities ◽  
Biological Properties ◽  
Northeastern Brazil ◽  
Acetylcholinesterase Inhibition ◽  
In Silico Studies ◽  
Phenolic Constituents

Ouratea fieldingiana is a native medicinal plant from Northeastern Brazil and many biological properties are due to the phenolic constituents. The objective of this work was performing the characterization of O. fieldingiana leaf constituents to correlate with antioxidant and anticholinesterase activities by in vitro and in silico studies and thus contribute to find new agents against Alzheimer’s disease. The high-performance liquid chromatography revealed the presence of the flavonoids rutin, isoquercitrin, kaempferol-3-O-rutinoside, quercetin, apigenin and amentoflavone. The antioxidant activities by the (2,2-diphenyl-1-picrylhydrazyl) (DPPH) and 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) methodologies, showed good results with half maximal inhibitory concentration (IC50) values ranging from 5.63 to 11.47 μg mL-1 and 2.72 to 23.71 μg mL-1, respectively. Acetylcholinesterase inhibition assay pointed out the flavone apigenin with best activity. Computational studies evaluated the interaction of flavonoids with the enzyme acetylcholinesterase co-crystallized with the galantamine, used as standard. All flavonoids exhibited binding energy greater than that of galantamine, but only apigenin showed strong interaction with the active site of the enzyme and other bind probably to different allosteric centers. Then, O. fieldingiana extract and flavonoids with good anti-radical activity and presenting a broad-spectrum action against acetylcholinesterase (AChE) enzyme ought to be tested in clinical studies to discover new neuro-therapeutic candidates.

Recent In Vitro and In Silico Advances in the Understanding of Intranasal Drug Delivery

2020 ◽  
Vol 26 ◽  
Author(s):  
John Chen ◽  
Andrew Martin ◽  
Warren H. Finlay
Keyword(s):  
Drug Delivery ◽  
In Silico ◽  
Local Drug Delivery ◽  
In Vivo Studies ◽  
Intranasal Drug Delivery ◽  
Nasal Sprays ◽  
In Silico Studies ◽  
Drug Delivery Devices

Background: Many drugs are delivered intranasally for local or systemic effect, typically in the form of droplets or aerosols. Because of the high cost of in vivo studies, drug developers and researchers often turn to in vitro or in silico testing when first evaluating the behavior and properties of intranasal drug delivery devices and formulations. Recent advances in manufacturing and computer technologies have allowed for increasingly realistic and sophisticated in vitro and in silico reconstructions of the human nasal airways. Objective: To perform a summary of advances in understanding of intranasal drug delivery based on recent in vitro and in silico studies. Conclusion: The turbinates are a common target for local drug delivery applications, and while nasal sprays are able to reach this region, there is currently no broad consensus across the in vitro and in silico literature concerning optimal parameters for device design, formulation properties and patient technique which would maximize turbinate deposition. Nebulizers are able to more easily target the turbinates, but come with the disadvantage of significant lung deposition. Targeting of the olfactory region of the nasal cavity has been explored for potential treatment of central nervous system conditions. Conventional intranasal devices, such as nasal sprays and nebulizers, deliver very little dose to the olfactory region. Recent progress in our understanding of intranasal delivery will be useful in the development of the next generation of intranasal drug delivery devices.

In-silico Studies of Isolated Phytoalkaloid Against Lipoxygenase: Study Based on Possible Correlation

2018 ◽  
Vol 21 (3) ◽  
pp. 215-221
Author(s):  
Haroon Khan ◽  
Muhammad Zafar ◽  
Helena Den-Haan ◽  
Horacio Perez-Sanchez ◽  
Mohammad Amjad Kamal
Keyword(s):  
In Silico ◽  
Docking Studies ◽  
In Vivo Studies ◽  
In Vitro Assays ◽  
Chronic Obstructive ◽  
Lipoxygenase Inhibitors ◽  
Lipoxygenase Inhibition ◽  
In Silico Studies

Aim and Objective: Lipoxygenase (LOX) enzymes play an important role in the pathophysiology of several inflammatory and allergic diseases including bronchial asthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, rheumatoid arthritis and chronic obstructive pulmonary disease. Inhibitors of the LOX are believed to be an ideal approach in the treatment of diseases caused by its over-expression. In this regard, several synthetic and natural agents are under investigation worldwide. Alkaloids are the most thoroughly investigated class of natural compounds with outstanding past in clinically useful drugs. In this article, we have discussed various alkaloids of plant origin that have already shown lipoxygenase inhibition in-vitro with possible correlation in in silico studies. Materials and Methods: Molecular docking studies were performed using MOE (Molecular Operating Environment) software. Among the ten reported LOX alkaloids inhibitors, derived from plant, compounds 4, 2, 3 and 1 showed excellent docking scores and receptor sensitivity. Result and Conclusion: These compounds already exhibited in vitro lipoxygenase inhibition and the MOE results strongly correlated with the experimental results. On the basis of these in vitro assays and computer aided results, we suggest that these compounds need further detail in vivo studies and clinical trial for the discovery of new more effective and safe lipoxygenase inhibitors. In conclusion, these results might be useful in the design of new and potential lipoxygenase (LOX) inhibitors.

In Vitro, In Silico and Ex Vivo Studies of Dihydroartemisinin Derivatives as Antitubercular Agents

2019 ◽  
Vol 19 (8) ◽  
pp. 633-644 ◽  
Author(s):  
Komal Kalani ◽  
Sarfaraz Alam ◽  
Vinita Chaturvedi ◽  
Shyam Singh ◽  
Feroz Khan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
In Silico ◽  
Ex Vivo ◽  
Virulent Strain ◽  
Infection Model ◽  
Mouse Bone Marrow ◽  
Significant Activity ◽  
Macrophage Infection ◽  
In Silico Studies

Introduction: As a part of our drug discovery program for anti-tubercular agents, dihydroartemisinin (DHA-1) was screened against Mtb H37Rv, which showed moderate anti-tubercular activity (>25.0 µg/mL). These results prompted us to carry out the chemical transformation of DHA-1 into various derivatives and study their antitubercular potential. Materials and Methods: DHA-1 was semi-synthetically converted into four new acyl derivatives (DHA-1A – DHA-1D) and in-vitro evaluated for their anti-tubercular potential against Mycobacterium tuberculosis H37Rv virulent strain. The derivatives, DHA-1C (12-O-(4-nitro) benzoyl; MIC 12.5 µg/mL) and DHA-1D (12-O-chloro acetyl; MIC 3.12µg/mL) showed significant activity against the pathogen. Results: In silico studies of the most active derivative (DHA-1D) showed interaction with ARG448 inhibiting the mycobacterium enzymes. Additionally, it showed no cytotoxicity towards the Vero C1008 cells and Mouse bone marrow derived macrophages. Conclusion: DHA-1D killed 62% intracellular M. tuberculosis in Mouse bone marrow macrophage infection model. To the best of our knowledge, this is the first-ever report on the antitubercular potential of dihydroartemisinin and its derivatives. Since dihydroartemisinin is widely used as an antimalarial drug; these results may be of great help in anti-tubercular drug development from a very common, inexpensive, and non-toxic natural product.

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