SYNTHESIS, In-vitro ANTIMICROBIAL, In-silico ADMET ANALYSIS AND DNA INTERACTION OF N-(8- HYDROXYQUINOLIN-5-YL)-4- METHYLBENZENESULFONAMIDE AND ITS METAL COMPLEXES: A COMBINED SPECTROSCOPY AND MOLECULAR DOCKING STUDIES

2021 ◽  
Vol 14 (01) ◽  
pp. 493-509
Author(s):  
Ruby Kharwar ◽  
Ritu B. Dixit
Keyword(s):  
Molecular Docking ◽  
Metal Complexes ◽  
In Silico ◽  
Dna Interaction ◽  
Docking Studies ◽  
Molecular Docking Studies ◽  
In Silico Admet

Synthesis, Biological Evaluation and Molecular Docking Studies of Novel Di-hydropyridine Analogs as Potent Antioxidants

2019 ◽  
Vol 19 (29) ◽  
pp. 2676-2686 ◽  
Author(s):  
Saddala Madhu Sudhana ◽  
Pradeepkiran Jangampalli Adi
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Binding Energies ◽  
Molecular Docking Studies ◽  
Metal Chelating ◽  
In Silico Admet ◽  
Dpph Method

Aims: The aim of this study is to synthesize, characterize and biological evaluation of 3-ethyl 5- methyl2-(2-aminoethoxy)-4-(2-chlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylate derivatives. Background: An efficient synthesis of two series of novel carbamate and sulfonamide derivatives of amlodipine, 3-ethyl 5-methyl 2-(2-aminoethoxy)-4-(2-chlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylate (amlodipine) 1 were chemical synthesized process. Materials & Methods: In this process, various chloroformates 2(a-e) and sulfonyl chlorides 4(a-e) on reaction with 1 in the presence of N,N–dimethylpiperazine as a base in THF at 50-550 oC, the corresponding title compounds 3(a-e) and 5(a-e) in high yields. Furthermore, the compounds 3(a-e) and 5(a-e) were evaluated for antioxidant activity (DPPH method), metal chelating activity, hemolytic activity, antioxidant assay (ABTS method), cytotoxicity, molecular docking and in silico ADMET properties. Result: Results revealed that 5a, 5e, 3d, 3a and 5c exhibited high antioxidant, metal chelating activities, but 5a, 5e and 3d exhibited low activity. The molecular docking studies and ADMET of suggested ligands showed the best binding energies and non-toxic properties. Conclusion: The present in silico and in vitro evaluations suggested that these dihydropyridine derivatives act as potent antioxidants and chelating agents which may be useful in treating metals induced oxidative stress associated diseases.

Computational Studies of bis-2-Oxoindoline Succinohydrazides and their In Vitro Cytotoxicity

2020 ◽  
Vol 16 (3) ◽  
pp. 270-280 ◽  
Author(s):  
Ravi Jarapula ◽  
Vishnu N. Badavath ◽  
Shriram Rekulapally ◽  
Sarangapani Manda
Keyword(s):  
Molecular Docking ◽  
Linear Regression ◽  
Cytotoxic Activity ◽  
In Silico ◽  
3D Qsar ◽  
Docking Studies ◽  
Egfr Inhibitors ◽  
Molecular Docking Studies ◽  
In Silico Admet

Background: The discovery of clinically relevant EGFR inhibitors for cancer therapy has proven to be a challenging task. To identify novel and potent EGFR inhibitors, the quantitative structure-activity relationship (QSAR) and molecular docking approach became a very useful and largely widespread technique for drug design. Methods: We performed the in vitro cytotoxic activity on HEPG-2 cell line and earlier on MCF-7 and A 549 by using MTT assay method. The development of 3D QSAR model of N1,N4-bis(2-oxoindolin-3- ylidene) succinohydrazides using the stepwise-backward variable methods to generate Multiple Linear Regression method elucidates the structural properties required for EGFR inhibitory activity and also perform the Molecular Docking studies on EGFR (PDB ID:1M17). Further, we analysed for Lipinski’s rule of five to evaluate the drug-likeness and established in silico ADMET properties. Results: The resulting cytotoxicity (IC50) values ranged from 9.34 to 100 μM and compared with cisplatin as a standard. Among the series of compounds, 6j showed good cytotoxic activity on HEPG-2 cell line with 9.34 μM, IC50 value. Most of the evaluated compounds showed good antitumor activity on HEPG-2 than MCF-7and A549. The developed 3D QSAR Multiple Linear Regression models are statistically significant with non-cross-validated correlation coefficient r2 = 0.9977, cross-validated correlation coefficient q2 = 0.902 and predicted_r2 = 0.9205. Molecular docking studies on EGFR (PDB ID: 1M17) results, compounds 6d, 6j and 6l showed good dock/PLP scores i.e. -81.28, -73.98 and -75.37, respectively, by interacting with Leu-694, Val-702 and Gly-772 amino acids via hydrophobic and hydrogen bonds with Asn818 and Met- 769. Further, we analysed drug-likeness and established in silico ADMET properties. Conclusion: The results of 3D QSAR studies suggest that the electrostatic and steric descriptors influence the cytotoxic activity of succinohydrazides. From the molecular docking studies, it is evident that hydrophobic, hydrogen and Van Der Waal’s interactions determine binding affinities. In addition to this, druglikeness and ADMET properties were analysed. It is evident that there is a correlation between the QSAR and docking results. Compound 6j was found to be too lipophilic due to its dihalo substitution on isatin nucleus, and can act as a lead molecule for further and useful future development of new EGFR Inhibitors.

scholarly journals Quinazolin-4-one derivatives lacking toxicity-producing attributes as glucokinase activators: design, synthesis, molecular docking, and in-silico ADMET prediction

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Saurabh C. Khadse ◽  
Nikhil D. Amnerkar ◽  
Manasi U. Dave ◽  
Deepak K. Lokwani ◽  
Ravindra R. Patil ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Enzyme Assay ◽  
Binding Free Energy ◽  
Docking Studies ◽  
Oral Glucose ◽  
Substitution Pattern ◽  
Glucokinase Activators ◽  
In Silico Admet

Abstract Background A small library of quinazolin-4-one clubbed thiazole acetates/acetamides lacking toxicity-producing functionalities was designed, synthesized, and evaluated for antidiabetic potential as glucokinase activators (GKA). Molecular docking studies were done in the allosteric site of the human glucokinase (PDB ID: 1V4S) enzyme to assess the binding mode and interactions of synthesized hits for best-fit conformations. All the compounds were evaluated by in vitro enzymatic assay for GK activation. Results Data showed that compounds 3 (EC50 = 632 nM) and 4 (EC50 = 516 nM) showed maximum GK activation compared to the standards RO-281675 and piragliatin. Based on the results of the in vitro enzyme assay, docking studies, and substitution pattern, selected compounds were tested for their glucose-lowering effect in vivo by oral glucose tolerance test (OGTT) in normal rats. Compounds 3 (133 mg/dL) and 4 (135 mg/dL) exhibited prominent activity by lowering the glucose level to almost normal, eliciting the results in parallel to enzyme assay and docking studies. Binding free energy, hydrogen bonding, and π–π interactions of most active quinazolin-4-one derivatives 3 and 4 with key amino acid residues of the 1V4S enzyme were studied precisely. Preliminary in-silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction was carried out using SwissADME and PreADMET online software which revealed that all the compounds have the potential to become orally active antidiabetic agents as they obeyed Lipinski's rule of five. Conclusion The results revealed that the designed lead could be significant for the strategic design of safe, effective, and orally bioavailable quinazolinone derivatives as glucokinase activators.

scholarly journals Synthesis, Characterization, Biological Screening, ADME and Molecular Docking Studies of 2-Phenyl Quinoline-4-Carboxamide Derivatives

2020 ◽  
Vol 32 (5) ◽  
pp. 1151-1157 ◽  
Author(s):  
P. Raghurama Shetty ◽  
G. Shivaraja ◽  
G. Krishnaswamy ◽  
K. Pruthviraj ◽  
Vivek Chandra Mohan ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Molecular Docking ◽  
Anticancer Activity ◽  
In Silico ◽  
Active Sites ◽  
Docking Studies ◽  
Spectrometric Analysis ◽  
Molecular Docking Studies ◽  
In Vitro Investigation

In this work, some 2-phenyl quinoline-4-carboxamide derivatives (5a-j) were synthesized via base catalyzed Pfitzinger reaction of isatin and acetophenone followed by C-N coupling reaction using POCl3 and assessed them for their in vitro antimicrobial and anticancer activity. The structure of newly synthesized compound were established by FT-IR, 1H & 13C NMR and Mass spectrometric analysis. The synthesized carboxamides were subjected to preliminary in vitro antibacterial activity as well as for antifungal activity. Results of antibacterial activity were compared with standard antibacterial (ciprofloxocin) and antifungal (fluconozole). Among the tested compounds, 5d, 5f and 5h exhibited promising activity with zone of inhibition ranging from 10 to 25 mm. Further, the anticancer activity determined using MTT assay against two cancer cell lines. Compounds 5b, 5d, 5f and 5h showed good anticancer activity among all the other derivatives. In order to correlate the in vitro results, in silico ADME and Molecular docking studies were carried out for (5a-j). ADME properties results showed that all the compounds obey rule of Five rule except 5a, 5e and 5g compound. Molecular docking studies of the synthesized compounds showed good binding affinity through hydrogen bond interactions with key residues on active sites as well as neighboring residues within the active site of chosen target proteins viz. antibacterial, antifungal and anticancer. Comparison of both results of in silico as well as in vitro investigation suggests that the synthesized compounds may act as potential antimicrobial as well as anticancer agents.

Design, Synthesis, In Silico and In Vitro Evaluation of Novel Pyrimidine Derivatives as EGFR Inhibitors

2020 ◽  
Vol 20 ◽  
Author(s):  
Gurubasavaraja S.P. Matada ◽  
Nahid Abbas ◽  
Prasad S. Dhiwar ◽  
Rajdeep Basu ◽  
Giles Devasahayam
Keyword(s):  
Breast Cancer ◽  
Molecular Docking ◽  
Anticancer Activity ◽  
In Silico ◽  
Docking Studies ◽  
Breast Cancer Cell Lines ◽  
Pyrimidine Derivatives ◽  
Molecular Docking Studies ◽  
Mcf 7

Background: The abnormal signaling from tyrosine kinase causes many types of cancers namely breast cancer, non-small cell lung cancer, and chronic myeloid leukemia. This research reports the in-silico, synthesis, and in-vitro study of novel pyrimidine derivatives as EGFR inhibitors. Objective: The objective of the research study is to discover more promising lead compounds using drug discovery process, in which the rational drug design is achieved by the molecular docking and virtual pharmacokinetic studies. Methods: The molecular docking studies were carried out using discovery studio 3.5-version software. The molecules with good docking and binding energy score were synthesized as well as their structures were confirmed by FT-IR, NMR, Mass and elemental analysis. Subsequently molecules were evaluated for their anticancer activity using MDA-MB-231, MCF-7 and A431 breast cancer cell lines by MTT and tyrosine kinase assay methodology. Results: Pyrimidine derivatives displayed anticancer activity. Particularly, compound R8 shows significant cytotoxicity against MDA-MB-231 with an IC50 18.5 ± 0.6 µM. Molecular docking studies proved that the compound R8 has good binding fitting by forming hydrogen bonds with amino acid residues at ATP binding sites of EGFR. Conclusion: Eight pyrimidine derivatives were designed, synthesized and evaluated against breast cancer cell lines. Compound R8 significantly inhibited the growth of MDA-MB-231 and MCF-7. Molecular docking studies reveled that compound R8 has good fitting by forming different Hydrogen bonding interactions with amino acids at ATP binding site of epidermal growth factor receptor target. Compound R8 was a promising lead molecule that showed better results as compared to other compounds in in-vitro studies.

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