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 Synthesis, Biological Assessment, and Structure Activity Relationship Studies of New Flavanones Embodying Chromene Moieties

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 544 ◽  
Author(s):  
Eman Assirey ◽  
Azhaar Alsaggaf ◽  
Arshi Naqvi ◽  
Ziad Moussa ◽  
Rawda M. Okasha ◽  
...  
Keyword(s):  
In Silico ◽  
Biological Assessment ◽  
Diffusion Method ◽  
Breast Adenocarcinoma ◽  
Cytotoxic Activities ◽  
Human Pathogens ◽  
Bacterial Strains ◽  
Human Carcinoma ◽  
In Silico Studies

Novel flavanones that incorporate chromene motifs are synthesized via a one-step multicomponent reaction. The structures of the new chromenes are elucidated by using IR, 1H-NMR, 13C-NMR, 1H-1H COSY, HSQC, HMBC, and elemental analysis. The new compounds are screened for their in vitro antimicrobial and cytotoxic activities. The antimicrobial properties are investigated and established against seven human pathogens, employing the agar well diffusion method and the minimum inhibitory concentrations. A majority of the assessed derivatives are found to exhibit significant antimicrobial activities against most bacterial strains, in comparison to standard reference drugs. Moreover, their cytotoxicity is appraised against four different human carcinoma cell lines: human colon carcinoma (HCT-116), human hepatocellular carcinoma (HepG-2), human breast adenocarcinoma (MCF-7), and adenocarcinoma human alveolar basal epithelial cell (A-549). All the desired compounds are subjected to in-silico studies, forecasting their drug likeness, bioactivity, and the absorption, distribution, metabolism, and excretion (ADME) properties prior to their synthetic assembly. The in-silico molecular docking evaluation of all the targeted derivatives is undertaken on gyrase B and the cyclin-dependent kinase. The in-silico predicted outcomes were endorsed by the in vitro studies.

Synthesis, Antimicrobial Evaluation and In silico Studies of Novel 2,4- disubstituted-1,3-thiazole Derivatives

2018 ◽  
Vol 16 (2) ◽  
pp. 160-173 ◽  
Author(s):  
Mir Mohammad Masood ◽  
Mohammad Irfan ◽  
Shadab Alam ◽  
Phool Hasan ◽  
Aarfa Queen ◽  
...  
Keyword(s):  
In Silico ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Docking Studies ◽  
Bacterial Strains ◽  
Thiazole Derivatives ◽  
Standard Drug ◽  
Hek 293 ◽  
In Silico Studies

Background: 2,4-disubstituted-1,3-thiazole derivatives (2a–j), (3a–f) and (4a–f) were synthesized, characterized and screened for their potential as antimicrobial agents. In the preliminary screening against a panel of bacterial strains, nine compounds showed moderate to potent antibacterial activity (IC50 = 13.7-90.8 μg/ml). </P><P> Methods: In the antifungal screening, compound (4c) displayed potent antifungal activity (IC50 = 26.5 &#181;g/ml) against Candida tropicalis comparable to the standard drug, fluconazole (IC50 = 10.5 &#181;g/ml). Based on in vitro antimicrobial results, compounds 2f, 4c and 4e were selected for further pharmacological investigations. Hemolytic activity using human red blood cells (hRBCs) and cytotoxicity by MTT assay on human embryonic kidney (HEK-293) cells revealed non-toxic nature of the selected compounds (2f, 4c and 4e). To ascertain their possible mode of action, docking studies with the lead inhibitors (2f, 4c and 4e) were performed using crystal structure coordinates of bacterial methionine aminopeptidases (MetAPs), an enzyme involved in bacterial protein synthesis and maturation. Results: The results of in vitro and in silico studies provide a rationale for selected compounds (2f, 4c and 4e) to be carried forward for further structural modifications and structure-activity relationship (SAR) studies against these bacterial infections. Conclusion: The study suggested binding with one or more key amino acid residues in the active site of Streptococcus pneumoniae MetAP (SpMetAP) and Escherichia coli MetAP (EcMetAP). In silico physicochemical properties using QikProp confirmed their drug likeliness.

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.

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.

Novel Spiro/non-Spiro Pyranopyrazoles: Eco-Friendly Synthesis, In-vitro Anticancer Activity, DNA Binding, and In-silico Docking Studies

2019 ◽  
Vol 15 (2) ◽  
pp. 257-267 ◽  
Author(s):  
Paritosh Shukla ◽  
Ashok Sharma ◽  
Leena Fageria ◽  
Rajdeep Chowdhury
Keyword(s):  
Anticancer Activity ◽  
Anticancer Agents ◽  
In Silico ◽  
Antimicrobial Agents ◽  
Docking Studies ◽  
Bioactive Molecules ◽  
Microwave Assisted Synthesis ◽  
Binding Affinities ◽  
In Silico Docking

Background: Cancer being a deadly disease, many reports of new chemical entities are available. Pyranopyrazole (PPZ) compounds have also been disclosed as bioactive molecules but mainly as antimicrobial agents. Based on one previous report and our interest in anticancer drug design, we decided to explore PPZs as anticancer agents. To the best of our knowledge, we found that a comprehensive study, involving synthesis, in-vitro biological activity determination, exploration of the mechanism of inhibition and finally in-silico docking studies, was missing in earlier reports. This is what the present study intends to accomplish. Methods: Ten spiro and eleven non-spiro PPZ molecules were synthesized by environment-friendly multicomponent reaction (MCR) strategy. After subjecting each of the newly synthesized molecules to Hep3b hepatocellular carcinoma cell lines assay, we selectively measured the Optical Density (OD) of the most active ones. Then, the compound exhibiting the best activity was docked against human CHK- 1 protein to get an insight into the binding affinities and a quick structure activity relationship (SAR) of the PPZs. Results: The two series of spiro and non-spiro PPZs were easily synthesized in high yields using microwave assisted synthesis and other methods. Among the synthesized compounds, most compounds showed moderate to good anticancer activity against the MTT assay. After performing the absorbance studies we found that the non-spiro molecules showed better apoptosis results and appeared to bind to DNA causing disruption in their structures. Finally, the docking results of compound 5h (having N,Ndimethylamino substituted moiety) clearly showed good binding affinities as predicted by our experimental findings. Conclusion: The paper describes a comprehensive synthesis, in-vitro and docking studies done on new PPZs. The newly synthesized series of spiro and non-spiro PPZs were found to possess antineoplasmic activity as evinced by the studies on hep3b cells. Also, the UV visible absorbance study gave clues to the possible binding of these molecules to the DNA. Docking studies corroborated well with the experimental results. Thus, these new molecules appear to be potential anticancer agents, but further studies are required to substantiate and elaborate on these findings.

scholarly journals Oleuropein modulates over-proliferation of keratinocytes in mice with imiquimodmediated psoriasis and inhibits differentiation of TH17 cells through the JAK3/STAT3 axis

2020 ◽  
Author(s):  
Quan Shi ◽  
Qi He ◽  
Weiming Chen ◽  
Jianwen Long ◽  
Bo Zhang
Keyword(s):  
T Cells ◽  
In Silico ◽  
Th17 Cells ◽  
Skin Lesions ◽  
Docking Studies ◽  
Inflammatory Disorder ◽  
T Helper 17 ◽  
In Silico Docking

IntroductionOleuropein (OLP) is polyphenol obtained from olive oil; it is proved in Chinese traditional medicine for its use in disorders including autoimmune and inflammatory disorders. Psoriasis (PSR) is an autoimmune and inflammatory disorder triggered by T-helper-17 (Th17) cells.Material and methodsWe developed an imiquimod (IMQ)-mediated PSR model in mice to study the anti-inflammatory role of OLP in psoriasis. The mice were given 50 mg/kg and 100 mg/kg dose of OLP. Histology was done to assess the inflammation of lesions. Western blot analysis was done for JAK3/STAT3 in isolated T cells, expression of RORgt was done by RT-PCR. The In silico molecular docking studies were done for interaction of OLP with target protein STAT3 and JAK3.ResultsTreatment of OLP attenuated proliferation in IMQ-mediated keratinocytes, improved infiltration of CD3+ cells in the skin lesions and in CD4+ and CD8+ T cells and also ameliorated the levels of cytokines. In in vitro studies in isolated T cells, OLP blocked the differentiation of Th17 cells and also the levels of IL-17 and the JAK3/STAT3 pathway. The in silico docking showed that OLP had potential binding affinity with JAK3 and STAT3 which was parallel to in vivo and in vitro findings.ConclusionsOLP ameliorates psoriasis skin lesions by blocking Th17-mediated inflammation. OLP may be an interesting molecule for treating autoimmunity in psoriasis.

scholarly journals Inhibition of Phosphodiesterase 5 Enzyme by Pterine- 6 Carboxylic Acid from Baphia nitida –Related to Erectile Dysfunction: Computational Kinetic

2020 ◽  
pp. 49-55
Author(s):  
Wopara, Iheanyichukwu ◽  
S. K. Mobisson ◽  
Egelege Aziemeola Pius ◽  
A. A. Uwakwe ◽  
M. O. Wegwu
Keyword(s):  
Erectile Dysfunction ◽  
Carboxylic Acid ◽  
Active Site ◽  
In Silico ◽  
Binding Pocket ◽  
Docking Studies ◽  
Drug Candidate ◽  
In Silico Docking ◽  
In Silico Studies ◽  
Phosphodiesterase 5

Treatment of erectile dysfunction is associated with inhibition of Phosphodiesterase 5 enzyme. This study deals with the evaluation of Pterin-6-carboxylic acid inhibitory activity on phosphodiesterase 5 (PDB ID: 4OEW) using in silico docking studies. Pterin-6-carboxylic acid from Baphia nitida was isolated using GC-MS and docked into PDE5 active site. The docking result showed that pterin-6-carboxylic acid bind to the active site of phosphodiesterase 5 with the binding energy value of -7.1 and 2.05A° - 2.23A° when compared with other compound found in the plant. Moreso, docking analysis with the ligand identified specific residues such as: Ile 778, Phe 820, Gln 817, Ser 815 and Gln 775 within the binding pocket which played an important role in the ligand binding affinity to the protein. Result from our In silico studies hypothesized that pterin-6-carboxylic acid can be an inhibitory agent for PDE5 protein which could be a potential drug candidate for the treatment of erectile dysfunction.

scholarly journals Synthesis and Characterization of Cobalt(III) and Copper(II) Complexes of 2-((E)-(6-Fluorobenzo[d]thiazol-2-ylimino) methyl)-4-chlorophenol: DNA Binding and Nuclease Studies—SOD and Antimicrobial Activities

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
K. Savithri ◽  
B. C. Vasantha Kumar ◽  
H. K. Vivek ◽  
H. D. Revanasiddappa
Keyword(s):  
Metal Complexes ◽  
Antimicrobial Activities ◽  
Spectroscopic Studies ◽  
Docking Studies ◽  
Bacterial Strains ◽  
Spectral Techniques ◽  
Light Reduction ◽  
Drug Candidates ◽  
Ft Ir

A bidentate (N- and O-) imine-based ligand (L1) and its metal complexes of types [CuII(L1)2] (C1), [CuII(L1)(Phen)] (C2), [CoIII(L1)2] (C3), and [CoIII(L1)(Phen)] (C4) (L1 = 2-((E)-(6-fluorobenzo[d]thiazol-2-ylimino)methyl)-4-chlorophenol and phen = 1,10-phenanthroline) were synthesized as potential chemotherapeutic drug candidates. The prepared complexes were structurally characterized by spectral techniques (NMR, FT-IR, LC-MS, EPR, and electronic absorption), thermogravimetric analysis (TGA/DTA), magnetic moment, and CHNO elemental analysis. Spectroscopic studies suggested the distorted octahedral structure for all complexes. In vitro bioassay studies include binding and nuclease activities of the ligand and its complexes with target calf thymus- (CT-) DNA were carried out by employing UV-Vis, fluorescence spectroscopy, viscosity, and gel electrophoresis techniques. The extent of binding propensity was determined quantitatively by Kb and Ksv values which revealed a higher binding affinity for C2 and C4 as compared to C1 and C3. In addition, the scavenging superoxide anion free radical (O∙-2) activity of metal complexes was determined by nitroblue tetrazolium (NBT) light reduction assay. Molecular docking studies with DNA and SOD enzyme were also carried out on these compounds. The antimicrobial study has shown that all the compounds are potential antibacterial agents against Gram-negative bacterial strains and better antifungal agents with respect to standard drugs used.

scholarly journals SYNTHESIS AND CHARACTERIZATION OF CYCLOHEXANE-1,3-DIONE DERIVATIVES AND THEIR IN SILICO AND IN VITRO STUDIES ON ANTIMICROBIAL AND BREAST CANCER ACTIVITY

2019 ◽  
pp. 311-320 ◽  
Author(s):  
RAJA CHINNAMANAYAKAR ◽  
EZHILARASI MR ◽  
PRABHA B ◽  
KULANDHAIVEL M
Keyword(s):  
Breast Cancer ◽  
Antimicrobial Activity ◽  
Anticancer Activity ◽  
Mtt Assay ◽  
In Silico ◽  
Biologically Active ◽  
Diffusion Method ◽  
Breast Adenocarcinoma ◽  
In Silico Docking

Objective: The objective of this study was to evaluate in silico and in vitro anticancer activity for synthesized cyclohexane-1,3-dione derivatives. Methods: The new series of cyclohexane-1,3-dione derivatives were synthesized based on the Michael addition reaction. Further, the structures of the synthesized compounds were confirmed by Fourier-transform infrared spectroscopy, 1H nuclear magnetic resonance (NMR), and 13C NMR spectral data. Then, the in silico molecular docking studies were carried out using AutoDock tool version 1.5.6 and AutoDock version 4.2.5.1 docking program. The antimicrobial activity was carried out using the agar disk diffusion method, and the in vitro anticancer activity was performed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for the synthesized compound. Results: In silico docking study, compound 5c showed good binding score and binding interactions with selected bacterial proteins and breast cancer protein. Further, compound (5a-5h) was tested for their antimicrobial activity and compound 5c was only tested for anticancer activity (human breast adenocarcinoma 3,4-methylenedioxyamphetamine-MB-231 cell line). Compound 5c was found to be the most active one of all the tested compounds. In the MTT assay compound, 5c showed the LC50 value of 10.31±0.003 μg/ml. In antimicrobial activity, the minimum inhibitory concentration of compound 5c is 2.5 mg/ml. Conclusion: An efficient synthesis of biologically active cyclohexane-1, 3-dione derivatives has been developed.

scholarly journals Synthesis, in vitro Antimicrobial Evaluation, Molecular Docking Studies and ADME Prediction of Furan-2-yl-Morpholinophenylpyrimidine Derivatives

2021 ◽  
Vol 33 (5) ◽  
pp. 1090-1098
Author(s):  
M.R. Ezhilarasi ◽  
A.B. Senthieel Khumar ◽  
P. Elavarasan
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Docking Studies ◽  
In Silico Docking ◽  
E Coli ◽  
Biological Studies ◽  
Antimicrobial Evaluation ◽  
Microbial Strains ◽  
In Silico Molecular Docking

A new series of novel 4-(furan-2-yl)-6-(4-morpholinophenyl)pyrimidine-amines (4a-c) were synthesized and characterized by elemental analysis and spectral analysis like IR, 1D 1H & 13C NMR. The synthesized compounds 4a-c were evaluated for their biological studies. The zone of inhibitions were examined for synthesized compounds 4a-c besides the identical set of microbial strains, especially that compound 4a against S. aureus, S. pyogenes, E. coli, compound 4b against P. aeruginosa has excellent antibacterial activity. Compound 4c shows good inhibition against C. albicans. Also in silico molecular docking and ADME predictions were carried for all the compounds. The docking studies were examined by two different proteins like 1UAG protein and 1OQA protein. in silico docking provides of the compounds have good docking score compared with the standard. In the ADME predictions all the compounds were met criteria. The synthesized compounds all of them obeyed the drug-likeness properties.

Sign in / Sign up

Export Citation Format

Share Document