scholarly journals Probing the Anti-Cancer Potency of Sulfated Galactans on Cholangiocarcinoma Cells Using Synchrotron FTIR Microspectroscopy, Molecular Docking, and In Vitro Studies

Marine Drugs ◽  
2021 ◽  
Vol 19 (5) ◽  
pp. 258
Author(s):  
Boonyakorn Boonsri ◽  
Kiattawee Choowongkomon ◽  
Buabarn Kuaprasert ◽  
Thanvarin Thitiphatphuvanon ◽  
Kittiya Supradit ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Drug Treatment ◽  
Combined Treatment ◽  
Dimerization Domain ◽  
Molecular Docking Study ◽  
Ftir Microspectroscopy ◽  
Sulfated Galactans ◽  
Biological Studies ◽  
Anti Cancer

Sulfated galactans (SG) isolated from red alga Gracilaria fisheri have been reported to inhibit the growth of cholangiocarcinoma (CCA) cells, which was similar to the epidermal growth factor receptor (EGFR)-targeted drug, cetuximab. Herein, we studied the anti-cancer potency of SG compared to cetuximab. Biological studies demonstrated SG and cetuximab had similar inhibition mechanisms in CCA cells by down-regulating EGFR/ERK pathway, and the combined treatment induced a greater inhibition effect. The molecular docking study revealed that SG binds to the dimerization domain of EGFR, and this was confirmed by dimerization assay, which showed that SG inhibited ligand-induced EGFR dimer formation. Synchrotron FTIR microspectroscopy was employed to examine alterations in cellular macromolecules after drug treatment. The SR-FTIR-MS elicited similar spectral signatures of SG and cetuximab, pointing towards the bands of RNA/DNA, lipids, and amide I vibrations, which were inconsistent with the changes of signaling proteins in CCA cells after drug treatment. Thus, this study demonstrates the underlined anti-cancer mechanism of SG by interfering with EGFR dimerization. In addition, we reveal that FTIR signature spectra offer a useful tool for screening anti-cancer drugs’ effect.

Structure-Based Design, Synthesis, Biological Evaluation and Molecular Docking Study of 4-Hydroxy-N'-methylenebenzohydrazide Derivatives Acting as Tyrosinase Inhibitors with Potentiate Anti-Melanogenesis Activities

2020 ◽  
Vol 16 (7) ◽  
pp. 892-902 ◽  
Author(s):  
Aida Iraji ◽  
Mahsima Khoshneviszadeh ◽  
Pegah Bakhshizadeh ◽  
Najmeh Edraki ◽  
Mehdi Khoshneviszadeh
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
Competitive Inhibition ◽  
Docking Study ◽  
Biological Evaluation ◽  
Primary Response ◽  
Ratio Method ◽  
Molecular Docking Study ◽  
Metal Chelating

Background: Melanogenesis is a process of melanin synthesis, which is a primary response for the pigmentation of human skin. Tyrosinase is a key enzyme, which catalyzes a ratelimiting step of the melanin formation. Natural products have shown potent inhibitors, but some of these possess toxicity. Numerous synthetic inhibitors have been developed in recent years may lead to the potent anti– tyrosinase agents. Objective: A number of 4-hydroxy-N'-methylenebenzohydrazide analogues with related structure to chalcone and tyrosine were constructed with various substituents at the benzyl ring of the molecule and evaluate as a tyrosinase inhibitor. In addition, computational analysis and metal chelating potential have been evaluated. Methods: Design and synthesized compounds were evaluated for activity against mushroom tyrosinase. The metal chelating capacity of the potent compound was examined using the mole ratio method. Molecular docking of the synthesized compounds was carried out into the tyrosine active site. Results: Novel 4-hydroxy-N'-methylenebenzohydrazide derivatives were synthesized. The two compounds 4c and 4g showed an IC50 near the positive control, led to a drastic inhibition of tyrosinase. Confirming in vitro results were performed via the molecular docking analysis demonstrating hydrogen bound interactions of potent compounds with histatidine-Cu+2 residues with in the active site. Kinetic study of compound 4g showed competitive inhibition towards tyrosinase. Metal chelating assay indicates the mole fraction of 1:2 stoichiometry of the 4g-Cu2+ complex. Conclusion: The findings in the present study demonstrate that 4-Hydroxy-N'- methylenebenzohydrazide scaffold could be regarded as a bioactive core inhibitor of tyrosinase and can be used as an inspiration for further studies in this area.

Synthesis and Anticancer Activity of 9-O-Pyrazole Alkyl Substituted Berberine Derivatives

2019 ◽  
Vol 18 (11) ◽  
pp. 1639-1648 ◽  
Author(s):  
Daipeng Xiao ◽  
Fen He ◽  
Dongming Peng ◽  
Min Zou ◽  
Junying Peng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Docking ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Human Lung Cancer ◽  
Drug Candidate ◽  
Molecular Docking Study ◽  
Protective Function ◽  
Anti Cancer ◽  
Cancer Activity

Background: Berberine (BBR), an isoquinoline plant alkaloid isolated from plants such as Coptis chinensis and Hydrastis canadensis, own multiple pharmacological activities. Objective: In this study, seven BBR derivatives were synthesized and their anticancer activity against HeLa cervical and A549 human lung cancer cell lines were evaluated in vitro. Methods: The anti-cancer activity was measured by MTT assay, and apoptosis was demonstrated by the annexin V-FITC/PI staining assay. The intracellular oxidative stress was investigated through DCFH-DA assay. The molecular docking study was carried out in molecular operating environment (MOE). Results: Compound B3 and B5 showed enhanced anti-cancer activity compared with BBR, the IC50 for compound B3 and B5 were significantly lower than BBR, and compound B3 at the concentration of 64 or 128 µM induced apoptosis in HeLa and A549 cell lines. The reactive oxygen species (ROS) was generated in both cell lines when treated with 100 µM of all the compounds, and compound B3 and B5 induced higher activity in the generation of ROS, while compound B3 exhibited the highest activity, these results are in accordance with the cytotoxicity results, indicating the cytotoxicity were mostly generated from the oxidative stress. In addition, molecular docking analysis showed that compound B3 had the greatest affinity with Hsp90. Upon binding, the protective function of Hsp90 was lost, which might explain its higher cytotoxicity from molecular interaction aspect. Conclusion: All the results demonstrated that compound B3 and B5 showed significantly higher anti-cancer ability than BBR, and compound B3 is a promising anticancer drug candidate.

scholarly journals Design, synthesis, molecular docking, and in vitro α-glucosidase inhibitory activities of novel 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines against yeast and rat α-glucosidase

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fariba Peytam ◽  
Ghazaleh Takalloobanafshi ◽  
Toktam Saadattalab ◽  
Maryam Norouzbahari ◽  
Zahra Emamgholipour ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Study ◽  
Rat Small Intestine ◽  
Molecular Docking Study ◽  
Design Synthesis ◽  
Mild Conditions ◽  
Glucosidase Inhibitors ◽  
Inhibitory Activities

AbstractIn an attempt to find novel, potent α-glucosidase inhibitors, a library of poly-substituted 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines 3a–ag have been synthesized through heating a mixture of 2-aminobenzimidazoles 1 and α-azidochalcone 2 under the mild conditions. This efficient, facile protocol has been resulted into the desirable compounds with a wide substrate scope in good to excellent yields. Afterwards, their inhibitory activities against yeast α-glucosidase enzyme were investigated. Showing IC50 values ranging from 16.4 ± 0.36 µM to 297.0 ± 1.2 µM confirmed their excellent potency to inhibit α-glucosidase which encouraged us to perform further studies on α-glucosidase enzymes obtained from rat as a mammal source. Among various synthesized 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines, compound 3k exhibited the highest potency against both Saccharomyces cerevisiae α-glucosidase (IC50 = 16.4 ± 0.36 μM) and rat small intestine α-glucosidase (IC50 = 45.0 ± 8.2 μM). Moreover, the role of amine moiety on the observed activity was studied through substituting with chlorine and hydrogen resulted into a considerable deterioration on the inhibitory activity. Kinetic study and molecular docking study have confirmed the in-vitro results.

scholarly journals Characterization of Possible α-Glucosidase Inhibitors from Trigonella stellata Extract Using LC–MS and In Silico Molecular Docking

Plants ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 208
Author(s):  
Ahlam Elwekeel ◽  
Dalia El Amir ◽  
Enas I. A. Mohamed ◽  
Elham Amin ◽  
Marwa H. A. Hassan ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Study ◽  
Docking Studies ◽  
Antidiabetic Activity ◽  
Flavonoid Glycosides ◽  
Total Phenolic ◽  
Cytotoxic Activities ◽  
Alcoholic Extract ◽  
Molecular Docking Study

The current study accentuates the significance of performing the multiplex approach of LC-HRESIMS, biological activity, and docking studies in drug discovery, taking into consideration a review of the literature. In this regard, the investigation of antioxidant and cytotoxic activities of Trigonella stellata collected from the Egyptian desert revealed a significant antioxidant capacity using DPPH with IC50 = 656.9 µg/mL and a moderate cytotoxicity against HepG2, MCF7, and CACO2, with IC50 values of 53.3, 48.3, and 55.8 µg/mL, respectively. The evaluation of total phenolic and flavonoid contents resulted in 32.8 mg GAE/g calculated as gallic acid equivalent and 5.6 mg RE/g calculated as rutin equivalent, respectively. Chemical profiling of T. stellata extract, using LC-HRESIMS analysis, revealed the presence of 15 metabolites, among which eleven compounds were detected for the first time in this species. Interestingly, in vitro testing of the antidiabetic activity of the alcoholic extract noted an α-glucosidase enzyme inhibitory activity (IC50 = 559.4 µg/mL) better than that of the standard Acarbose (IC50 = 799.9 µg/mL), in addition to a moderate inhibition of the α-amylase enzyme (IC50 = 0.77 µg/mL) compared to Acarbose (IC50 = 0.21 µg/mL). α-Glucosidase inhibition was also virtualized by binding interactions through the molecular docking study, presenting a high binding activity of six flavonoid glycosides, as well as the diterpenoid compound graecumoside A and the alkaloid fenugreekine. Taken together, the conglomeration of LC-HRESIMS, antidiabetic activity, and molecular docking studies shed light on T. stellata as a promising antidiabetic herb.

scholarly journals Synthesis, Characterization, in vitro Antimicrobial Evaluation and in silico Molecular Docking and ADME Prediction of 4-Chlorophenyl Furfuran Derivatives bearing Pyrazole Moieties

2020 ◽  
Vol 32 (6) ◽  
pp. 1482-1490
Author(s):  
Manju Mathew ◽  
Raja Chinnamanayakar ◽  
Ezhilarasi Muthuvel Ramanathan
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Docking Study ◽  
Docking Studies ◽  
Moderate Activity ◽  
Molecular Docking Study ◽  
Adme Prediction ◽  
Antimicrobial Studies ◽  
In Silico Molecular Docking

A series of 1-(5-(5-(4-chlorophenyl)furan-2-yl)-4,5-dihyropyrazol-1-yl ethanone (5a-h) was synthesized through E-(3-(5-(4-chloro-phenyl)furan-2-yl)-1-phenylprop-2-en-1-one (3a-h) with hydrazine monohydrate and sodium acetate. Totally, eight compounds were synthesized and their structures were elucidated by infrared, 1H & 13C NMR, elemental analysis, antimicrobial studies, in silico molecular docking studies and also in silico ADME prediction. Antimicrobial studies of the synthesized compounds showed good to moderate activity against the all the stains compared with standard drugs. in silico Molecular docking study was carried out using bacterial protein and BC protein. Synthesized compounds (5a-h) showed good docking score compared with ciprofloxacin. Antimicrobial study was carried out for 4-chlorophenyl furfuran pyrazole derivatives (5a-h). The results of assessment of toxicities, drug likeness and drug score profiles of compounds (5a-j) are promising

scholarly journals Functionalization of 3-chloroformylcoumarin to coumarin Schiff bases using reusable catalyst: an approach to molecular docking and biological studies

2018 ◽  
Vol 5 (5) ◽  
pp. 172416 ◽  
Author(s):  
Suresh S. Kumbar ◽  
Kallappa M. Hosamani ◽  
Gangadhar C. Gouripur ◽  
Shrinivas D. Joshi
Keyword(s):  
Molecular Docking ◽  
Heterogeneous Catalysts ◽  
Vero Cells ◽  
Reusable Catalyst ◽  
Subsequent Investigation ◽  
Antimicrobial Studies ◽  
Cytotoxicity Studies ◽  
Biological Studies ◽  
Simplified Procedure

Recently, heterogeneous catalysts have been explored eximiously in the synthesis of heterocyclic compounds. Therefore, here we used solid-supported heterogeneous silica sulfuric acid as a catalyst for the synthesis of Schiff's base of 3-chloroformylcoumarin in view of simplified procedure, reusability and acceptable efficiency, which are required in organic synthesis. An efficient and facile methodology is preferred for synthesis of a class of chromeno-3-substituted derivatives ( 1a–1l ) with good yields. The molecular docking results showed excellent binding interactions with the Mycobacterium tuberculosis InhA-D148G mutant (PDB: 4DQU). The same biomolecules were screened for their in vitro anti-tubercular activity against the M.tb H37Rv strain and antimicrobial studies. Physico-chemistry, toxicity prediction with IC50 value and bioactivity score were also calculated for title compounds. Most active compounds were further tested for cytotoxicity studies and exhibited low-level cytotoxicity against Vero cells. The suggested conjugates are promising lead compounds for the subsequent investigation in search of new anti-tubercular agents. All the conjugates were obtained within the range and followed the Lipinski rule of 5, indicating more ‘drug-like’ nature.

Design, Synthesis, Molecular Docking and Biological Studies of New Heterocyclic Compounds Derived from -Diketonesas Novel EGFR and Pim-1 Inhibitors Endowed with Antitumor Activity

2022 ◽  
Vol 22 ◽  
Author(s):  
Rafat Milad Mohareb ◽  
Noha M. Asaad Bagato ◽  
Ibrahim Taha Radwan
Keyword(s):  
Molecular Docking ◽  
Antitumor Activity ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Diethyl Malonate ◽  
Binding Mode ◽  
Binding Modes ◽  
Binding Interactions ◽  
Biological Studies

Background: Cancer is a disease illustrated by a shift in the controlled mechanisms that control both cell proliferation and differentiation. It is regarded as a prime health problem worldwide, leading cause of human death-rate exceeded only by cardiovascular diseases. Many reported work was concerned with the discovery of new antitumor compounds this encourage us to synthesis new anticancer agents. Objective: In this work, we are aiming to synthesize target molecules from 1,3-dicarbonyl compounds through many heterocyclization reactions. Method: The reaction of either 4-methylaniline (1a) or 1-naphthylamine (1b) with diethyl malonate (2) gave the anilide derivatives 3a and 3b, respectively. The latter products underwent a series of heterocyclization reactions to give the pyridine, pyran andthiazole derivatives which confirmed with the required spectral data. Results: Thein-vitro antitumor evaluations of the newly synthesized products against four cancer cell lines MCF-7, NCI-H460, SF-268 and WI 38 as normal cell line were screened and the data revealed that compounds 11a, 18b, 18c and 20d showed high antitumor activity and 20dindividualize with potential antitumor activity towards cell lines with lowest cytotoxicity effect. Both EGFR and PIM-1 enzyme inhibition were investigated for the compound 20d and his inhibition effect was promising for each enzyme showing IC50=45.67 ng and 553.3 ng for EGFR and PIM-1, respectively. Conclusion: Molecular docking results of compound 20d showed a strong binding interactions on both enzymes, where, good binding modes obtained on case of EGFR, which closely similar to the binding mode of standard Erlotinib. While, 20d showed complete superimposition binding interactions with VRV-cocrystallized ligand of PIM-1 that may expounds the in-vitro antitumor activity.

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