scholarly journals ANTICANCER ACTIVITY OF Β-SITOSTEROL FROM PLECTRANTHUS AMBOINICUS (LOUR. SPRENG.) LEAVES: IN VITRO AND IN SILICO STUDIES

2017 ◽  
Vol 10 (5) ◽  
pp. 306
Author(s):  
Denny Satria ◽  
Poppy Anjelisa Zaitun Hasibuan ◽  
Panal Sitorus
Keyword(s):  
In Silico ◽  
Estrogen Receptor Alpha ◽  
In Vitro Study ◽  
Three Dimensions ◽  
Three Dimension ◽  
Docking Score ◽  
In Silico Docking ◽  
In Silico Studies ◽  
Her 2

Objective: β-sitosterol is the steroid compound which is an important nutrient in the diet meal, hydrophobic and soluble in organic solvents and considered as a good biomarker due to its biological activity.Methods: In vitro study was using 2,5-diphenyl tetrazolium bromide method towards T47D, MCF-7, HeLa, and WiDr cell lines. In silico docking using PLANTS program and visualized by Yasara program. The model of three dimension enzyme structures used in this research were epidermal growth factor receptor (EGFR), phosphatidylinositol-3-kinase (PI3K), estrogen receptor-alpha (ER-α), ER-beta (ER-β), and human EGFR 2 (HER-2). Two and three dimensions of β-sitosetrol, ZSTK474, and tamoxifen as the standard were generated using Marvin Sketch program.Results: β-sitosterol was found to have inhibitory concentration 50% of 0.55; 0.87; 0.76, and 0.99 mM. β-sitosterol and ZSTK474 were inhibited EGFR and PI3K with docking score −92.8195; −91.7920 and −91.7470; −94.7491 β-sitosterol and tamoxifen were inhibited ER-α, ER-β and HER-2 with docking score −78.5570; −89.535, −68.7717; −52.008 and −90.4908; −50.5576, respectively.Conclusion: Based on the results above that shows β-sitosterol provide effective as anticancer.Keywords: β-sitosterol, Inhibitor, Anticancer, In vitro, In silico.

scholarly journals MCF-7 Human Breast Adenocarcinoma Anticancer and Antimicrobial, in silico Docking and ADME Prediction Studies of Furan Moiety Containing Substituted 2-Aminopyrimidine Derivatives

2021 ◽  
Vol 33 (7) ◽  
pp. 1504-1512
Author(s):  
Manju Mathew ◽  
Muthuvel Ramanathan Ezhilarasi
Keyword(s):  
In Silico ◽  
Antimicrobial Activities ◽  
Docking Studies ◽  
Breast Adenocarcinoma ◽  
Bacterial Strains ◽  
In Silico Docking ◽  
In Silico Studies ◽  
Furan Moiety ◽  
Different Strains

A series of 4(5-(4-chlorophenyl)furan-2-yl)-6-phenylpyrimidin-2-amine derivatives (5a-h) were synthesized from 2-(4-chlorophenyl)-5-styrylfuran (3a-h) with guanidine nitrate in absolute ethanol under conventional method and evaluated for their in vitro anticancer, antimicrobial activities and in silico studies. The chemical structure of the furan moiety containing substituted amino pyrimidine derivatives (5a-h) were elucidated from spectroscopic analysis like infrared, 1H & 13C NMR spectral data and CHN analysis. in silico docking studies were predicted for the synthesized compounds (5a-h) using bacterial protein 1UAG and in silico ADME predictions were also carried for the synthesized compounds (5a-h). The in vitro anticancer study was carried the compound 5b by MMT assay. Compound 5b shows the LC50 value of 120.15 ± 0.003 μg/mL. in vitro Antimicrobial activities were screened for the compounds (5a-h) using different strains. Compound 5h has electron withdrawing group in benzene ring substituted in the para position showed good antimicrobial activity against all the bacterial strains and fungal strains. in silico studies, compound 5h shows excellent docking score (-9.7 kcal/mol) compared with ciprofloxacin (-7.8 kcal/mol).

scholarly journals IN SILICO DOCKING ROSELLE (HIBISCUS SABDARIFFA L.) CALYCES FLAVONOIDS AS ANTIMALARIAL AGAINST PLASMEPSIN 1 AND PLASMEPSIN 2

2017 ◽  
Vol 10 (10) ◽  
pp. 183 ◽  
Author(s):  
Nerdy Nerdy
Keyword(s):  
Partition Coefficient ◽  
In Silico ◽  
Two Dimensions ◽  
Three Dimensions ◽  
Protein Data Bank Code ◽  
Hibiscus Sabdariffa ◽  
Ant System ◽  
Operation System ◽  
Docking Score ◽  
In Silico Docking

  Objective: Study the in silico plasmepsin 1 and plasmepsin 2 inhibition antimalarial effects of roselle (Hibiscus sabdariffa L.) calyces flavonoids compared to artemisinin as astandard compound for antimalarial to inhibit plasmepsin 1 and plasmepsin 2.Methods: Partition coefficient was predicted by the ChemDraw Ultra. In silico molecular docking was done by Protein-Ligand ANT System. Visualization was done by Yet Another Scientific Artificial Reality Application. Connector for Windows operation system to Linux operation system was done by Co Pendrive Linux. Three dimensions enzyme structure models used in this research were plasmepsin 1 and plasmepsin 2 with the protein data bank code 3QS1 and 1LEE obtained through the website http://www.rcsb.org/pdb. Two dimensions and three dimensions conformation model of compounds were generated by Marvin Sketch.Results: Partition coefficient of roselle calyces flavonoids quercetin, gossypetin, hibiscetin, and artemisinin, respectively, were 0.58, –0.44, –0.43, and 3.17. Higher partition coefficient means easier to penetrate into the cell. Docking score of roselle calyces flavonoids quercetin, gossypetin, hibiscetin, and artemisinin to plasmepsin 1, respectively, were –70.1989, –70.9454, –70.5870, and –61.7685 to plasmepsin 2, respectively, were –73.8620, –76,0086, –78.8930, and –61.7437. Lower docking score means a better potential activity to protein enzyme.Conclusion: Roselle calyces flavonoids (quercetin, gossypetin, and hibiscetin) show the stronger activity than artemisinin to inhibit plasmepsin 1 and plasmepsin 2. 

scholarly journals Dual BACE1 and Cholinesterase Inhibitory Effects of Phlorotannins from Ecklonia cava—An In Vitro and in Silico Study

Marine Drugs ◽  
2019 ◽  
Vol 17 (2) ◽  
pp. 91 ◽  
Author(s):  
Jinhyuk Lee ◽  
Mira Jun
Keyword(s):  
In Silico ◽  
In Vitro Study ◽  
Kinetic Studies ◽  
Binding Energies ◽  
Ecklonia Cava ◽  
Hydroxyl Groups ◽  
Inhibitory Effects ◽  
In Silico Docking ◽  
Ache Inhibitors

Alzheimer′s disease (AD) is one of the most common neurodegenerative diseases with a multifactorial nature. β-Secretase (BACE1) and acetylcholinesterase (AChE), which are required for the production of neurotoxic β-amyloid (Aβ) and the promotion of Aβ fibril formation, respectively, are considered as prime therapeutic targets for AD. In our efforts towards the development of potent multi-target, directed agents for AD treatment, major phlorotannins such as eckol, dieckol, and 8,8′-bieckol from Ecklonia cava (E. cava) were evaluated. Based on the in vitro study, all tested compounds showed potent inhibitory effects on BACE1 and AChE. In particular, 8,8′-bieckol demonstrated the best inhibitory effect against BACE1 and AChE, with IC50 values of 1.62 ± 0.14 and 4.59 ± 0.32 µM, respectively. Overall, kinetic studies demonstrated that all the tested compounds acted as dual BACE1 and AChE inhibitors in a non-competitive or competitive fashion, respectively. In silico docking analysis exhibited that the lowest binding energies of all compounds were negative, and specifically different residues of each target enzyme interacted with hydroxyl groups of phlorotannins. The present study suggested that major phlorotannins derived from E. cava possess significant potential as drug candidates for therapeutic agents against AD.

scholarly journals Facile One-Pot Multicomponent Synthesis of Pyrazolo-Thiazole Substituted Pyridines with Potential Anti-Proliferative Activity: Synthesis, In Vitro and In Silico Studies

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3103
Author(s):  
Islam H. El El Azab ◽  
Rania B. Bakr ◽  
Nadia A. A. Elkanzi
Keyword(s):  
Cell Lines ◽  
In Silico ◽  
Topoisomerase Ii ◽  
Human Cancer ◽  
Docking Simulation ◽  
Cytotoxic Potential ◽  
One Pot ◽  
In Silico Docking ◽  
In Silico Studies

Pyrazolothiazole-substituted pyridine conjugates are an important class of heterocyclic compounds with an extensive variety of potential applications in the medicinal and pharmacological arenas. Therefore, herein, we describe an efficient and facile approach for the synthesis of novel pyrazolo-thiazolo-pyridine conjugate 4, via multicomponent condensation. The latter compound was utilized as a base for the synthesis of two series of 15 novel pyrazolothiazole-based pyridine conjugates (5–16). The newly synthesized compounds were fully characterized using several spectroscopic methods (IR, NMR and MS) and elemental analyses. The anti-proliferative impact of the new synthesized compounds 5–13 and 16 was in vitro appraised towards three human cancer cell lines: human cervix (HeLa), human lung (NCI-H460) and human prostate (PC-3). Our outcomes regarding the anti-proliferative activities disclosed that all the tested compounds exhibited cytotoxic potential towards all the tested cell lines with IC50 = 17.50–61.05 µM, especially the naphthyridine derivative 7, which exhibited the most cytotoxic potential towards the tested cell lines (IC50 = 14.62–17.50 µM) compared with the etoposide (IC50 = 13.34–17.15 µM). Moreover, an in silico docking simulation study was performed on the newly prepared compounds within topoisomerase II (3QX3), to suggest the binding mode of these compounds as anticancer candidates. The in silico docking results indicate that compound 7 was a promising lead anticancer compound which possesses high binding affinity toward topoisomerase II (3QX3) protein.

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.

scholarly journals Scaffold Repurposing of In-House Small Molecule Candidates Leads to Discovery of First-in-Class CDK-1/HER-2 Dual Inhibitors: In Vitro and In Silico Screening

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5324
Author(s):  
Ahmed Elkamhawy ◽  
Usama M. Ammar ◽  
Sora Paik ◽  
Magda H. Abdellattif ◽  
Mohamed H. Elsherbeny ◽  
...  
Keyword(s):  
In Silico ◽  
Docking Study ◽  
In Vitro Cytotoxicity ◽  
Cyclin B ◽  
Binding Modes ◽  
Molecular Docking Study ◽  
In Silico Studies ◽  
Her 2 ◽  
Inhibitory Activities

Recently, multitargeted drugs are considered a potential approach in treating cancer. In this study, twelve in-house indole-based derivatives were preliminary evaluated for their inhibitory activities over VEGFR-2, CDK-1/cyclin B and HER-2. Compound 15l showed the most inhibitory activities among the tested derivatives over CDK-1/cyclin B and HER-2. Compound 15l was tested for its selectivity in a small kinase panel. It showed dual selectivity for CDK-1/cyclin B and HER-2. Moreover, in vitro cytotoxicity assay was assessed for the selected series against nine NCI cell lines. Compound 15l showed the most potent inhibitory activities among the tested compounds. A deep in silico molecular docking study was conducted for compound 15l to identify the possible binding modes into CDK-1/cyclin B and HER-2. The docking results revealed that compound 15l displayed interesting binding modes with the key amino acids in the binding sites of both kinases. In vitro and in silico studies demonstrate the indole-based derivative 15l as a selective dual CDK-1 and HER-2 inhibitor. This emphasizes a new challenge in drug development strategies and signals a significant milestone for further structural and molecular optimization of these indole-based derivatives in order to achieve a drug-like property.

The Morelloflavone as Potential Anticancer Agent against MCF-7 Breast Cancer Cell Lines: In vitro and In silico Studies

2021 ◽  
Vol 18 ◽  
Author(s):  
Darwati ◽  
Nurlelasari ◽  
Tri Mayanti ◽  
Nurul Ambardhani ◽  
Dikdik Kurnia
Keyword(s):  
Cancer Cell ◽  
Active Compound ◽  
In Silico ◽  
Caspase 9 ◽  
Cancer Cell Growth ◽  
Tnf Α ◽  
In Silico Studies ◽  
Her 2 ◽  
Mcf 7

Background: Breast cancer is a leading cause of death among people. Nowadays, the development of cancer treatment is focused on investigating anticancer drugs from natural compounds. Various methods, including in vitro, in vivo, and in silico ways, are used to assess potential. Exploring bioactive compounds from medicinal plant origin lies in their affordability and convenience to improve efficacy and minimize side effects. The Garcinia genus contains bioactive compounds such as xanthones, benzophenones, triterpenes, biflavonoids, and benzoquinones. Purpose: Investigate an active compound that can inhibit cancer cell growth and proteins that contribute to cancer cell growth, such as Caspase-9, TNF-α, ER-α, and HER-2. Methods: This study is divided into three steps. The first step is the isolation of the active compound from G. cymosa. The second step is an assessment of cytotoxic activity against MCF-7 cell by MTT assay, and the last one is an investigation of the molecular mechanism of an active compound against Caspase-9, TNF-α, ER-α, and HER-2 by in silico studies using various programs such as PyRx 0.8, PYMOL, and discovery studio programs. Results: Morelloflavone from G. cymosa stem barks has anticancer activity (55.84 µg/mL) eight times lower than doxorubicin (6.99 µg/mL), but it can block the activity of Caspase-9, TNF-α, ER-α, and HER-2. The binding affinity of morelloflavone is the strongest of all ligands. Conclusion: The natural flavonoid morelloflavone potencies as a new lead compound candidate for anticancer agent inhibit mode action mechanism of Caspase-9, TNF-α, ER-α, and HER-2, respectively.

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.

scholarly journals Combining In Silico and In Vitro Studies to Evaluate the Acetylcholinesterase Inhibitory Profile of Different Accessions and the Biomarker Triterpenes of Centella asiatica

Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3353
Author(s):  
Nor Atiqah Jusril ◽  
Ain Nur Najihah Muhamad Juhari ◽  
Syahrul Imran Abu Bakar ◽  
Wan Mazlina Md Saad ◽  
Mohd Ilham Adenan
Keyword(s):  
Inhibitory Activity ◽  
In Silico ◽  
Active Sites ◽  
In Vitro Study ◽  
Centella Asiatica ◽  
Ache Inhibitor ◽  
Asiatic Acid ◽  
In Silico Docking ◽  
Ache Inhibitory Activity

Alzheimer’s disease (AD) is a neurodegenerative disease and the most cause of dementia in elderly adults. Acetylcholinesterase (AChE) is an important beneficial target for AD to control cholinergic signaling deficit. Centella asiatica (CA) has proven to be rich with active ingredients for memory enhancement. In the present study, the chemical profiling of three accession extracts of CA namely SECA-K017, SECA-K018, and, SECA-K019 were performed using high-performance liquid chromatography (HPLC). Four biomarker triterpene compounds were detected in all CA accessions. Quantitative analysis reveals that madecassoside was the highest triterpene in all the CA accessions. The biomarker compounds and the ethanolic extracts of three accessions were investigated for their acetylcholinesterase (AChE) inhibitory activity using Ellman’s spectrophotometer method. The inhibitory activity of the triterpenes and accession extracts was compared with the standard AChE inhibitor eserine. The results from the in vitro study showed that the triterpene compounds exhibited an AChE inhibitory activity with the half-maximal inhibitory concentration (IC50) values between 15.05 ± 0.05 and 59.13 ± 0.18 µg/mL. Asiatic acid was found to possess strong AChE inhibitory activity followed by madecassic acid. Among the CA accession extracts, SECA-K017 and SECA-K018 demonstrated a moderate AChE inhibitory activity with an IC50 value of 481.5 ± 0.13 and 763.5 ± 0.16 µg/mL, respectively from the in silico docking studies, it is observed that asiatic acid and madecassic acid showed very good interactions with the active sites and fulfilled docking parameters against AChE. The present study suggested that asiatic acid and madecassic acid in the CA accessions could be responsible for the AChE inhibitory action and could be used as markers to guide further studies on CA as potential natural products for the treatment of AD.

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.

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