3D-QSAR, molecular docking and in silico ADMET studies of propiophenone derivatives with anti-HIV-1 protease activity

2021 ◽  
Author(s):  
Milan Jovanović ◽  
Nemanja Turković ◽  
Branka Ivković ◽  
Zorica Vujić ◽  
Katarina Nikolić ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Protease Activity ◽  
3D Qsar ◽  
In Silico Admet ◽  
Anti Hiv ◽  
Hiv 1

Molecular Docking, Synthesis and anti-HIV-1 Protease Activity of Novel Chalcones

2020 ◽  
Vol 26 (8) ◽  
pp. 802-814 ◽  
Author(s):  
Nemanja Turkovic ◽  
Branka Ivkovic ◽  
Jelena Kotur-Stevuljevic ◽  
Milica Tasic ◽  
Bojan Marković ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Molecular Docking ◽  
Chemical Synthesis ◽  
Protease Activity ◽  
Molecular Mechanisms ◽  
Replication Cycle ◽  
Low Molecular Weight ◽  
Chalcone Derivatives ◽  
Anti Hiv ◽  
Hiv 1

Background: Since the beginning of the HIV/AIDS epidemic, 75 million people have been infected with the HIV and about 32 million people have died of AIDS. Investigation of the molecular mechanisms critical to the HIV replication cycle led to the identification of potential drug targets for AIDS therapy. One of the most important discoveries is HIV-1 protease, an enzyme that plays an essential role in the replication cycle of HIV. Objective: The aim of the present study is to synthesize and investigate anti-HIV-1 protease activity of some chalcone derivatives with the hope of discovering new lead structure devoid drug resistance. Methods: 20 structurally similar chalcone derivatives were synthesized and their physico-chemical characterization was performed. Binding of chalcones to HIV-1 protease was investigated by fluorimetric assay. Molecular docking studies were conducted to understand the interactions. Results: The obtained results revealed that all compounds showed anti-HIV-1 protease activity. Compound C1 showed the highest inhibitory activity with an IC50 value of 0.001 μM, which is comparable with commercial product Darunavir. Conclusion: It is difficult to provide general principles of inhibitor design. Structural properties of the compounds are not the only consideration; ease of chemical synthesis, low molecular weight, bioavailability, and stability are also of crucial importance. Compared to commercial products the main advantage of compound C1 is the ease of chemical synthesis and low molecular weight. Furthermore, compound C1 has a structure that is different to peptidomimetics, which could contribute to its stability and bioavailability.

Molecular Modeling Studies on 2,4-Disubstituted Imidazopyridines as Anti-Malarials: Atom-Based 3D-QSAR, Molecular Docking, Virtual Screening, In-Silico ADMET and Theoretical Analysis

2021 ◽  
pp. 2150012
Author(s):  
Suraj N. Mali ◽  
Anima Pandey
Keyword(s):  
Molecular Docking ◽  
Molecular Modeling ◽  
Virtual Screening ◽  
In Silico ◽  
Energy Gap ◽  
3D Qsar ◽  
Modeling Studies ◽  
In Vitro Investigation ◽  
In Silico Admet ◽  
Molecular Modeling Studies

Malarial parasites have been reported for moderate-high resistance towards classical antimalarial agents and henceforth development of newer novel chemical entities targeting multiple targets rather than targeting single target will be a highly promising strategy in antimalarial drug discovery. Herein, we carried out molecular modeling studies on 2,4-disubstituted imidazopyridines as anti-hemozoin formation inhibitors by using Schrödinger’s molecular modeling package (2020_4). We have developed statistically robust atom-based 3D-QSAR model (training set, [Formula: see text]; test set, [Formula: see text]; [Formula: see text] [Formula: see text]; root-mean-square error, [Formula: see text]; standard deviation, [Formula: see text]). Our molecular docking, in-silico ADMET analysis showed that dataset molecule 37, has highly promising results. Our ligand-based virtual screening resulted in top five ZINC hits, among them ZINC73737443 hit was observed with lesser energy gap, i.e. 7.85[Formula: see text]eV, higher softness value (0.127[Formula: see text]eV), and comparatively good docking score of [Formula: see text]10.2[Formula: see text]kcal/mol. Our in-silico analysis for a proposed hit, ZINC73737443 showed that this molecule has good ADMET, in-silico nonames toxic as well as noncarcinogenic profile. We believe that further experimental as well as the in-vitro investigation will throw more lights on the identification of ZINC73737443 as a potential antimalarial agent.

In silico study on indole derivatives as anti HIV-1 agents: a combined docking, molecular dynamics and 3D-QSAR study

2013 ◽  
Vol 37 (8) ◽  
pp. 1001-1015 ◽  
Author(s):  
Anand Balupuri ◽  
Changdev G. Gadhe ◽  
Pavithra K. Balasubramanian ◽  
Gugan Kothandan ◽  
Seung Joo Cho
Keyword(s):  
Molecular Dynamics ◽  
In Silico ◽  
3D Qsar ◽  
Indole Derivatives ◽  
Qsar Study ◽  
In Silico Study ◽  
Anti Hiv ◽  
Hiv 1

scholarly journals Thermochemical, PASS, Molecular Docking, Drug-Likeness and In Silico ADMET Prediction of Cytidine Derivatives against HIV-1 Reverse Transcriptase

2021 ◽  
Vol 72 (3) ◽  
pp. 159-178
Author(s):  
Sarkar Mohammad Abe Kawsar ◽  
Mohammed Anowar Hosen ◽  
Tasneem Sultana Chowdhury ◽  
Kazi Masud Rana ◽  
Yuki Fujii ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Molecular Docking ◽  
Reverse Transcriptase ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
In Silico ◽  
In Silico Admet ◽  
Immunodeficiency Virus ◽  
Hiv 1

In recent, millions of people are living with the human immunodeficiency virus type 1 (HIV-1), which causes acquired immunodeficiency syndrome. HIV-1 reverse transcriptase (RT) is one of the main viral targets for HIV-1 inhibition. Pyrimidine nucleoside derivative, 3′-azido-3′-deoxythymidine (AZT) is a highly active nucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). In this work, hydroxyl (-OH) groups of cytidine structure were modified with different aliphatic and aromatic groups to get 5´-O-acyl- and 2´,3´-di-O-acyl derivatives and then employed for molecular modeling, molecular docking, biological prediction, and pharmacological studies. Herein, we relate the optimization of cytidine and its acylated analogues applying density functional theory (DFT) with B3LYP/3-21G level theory to explore their thermochemical and molecular electrostatic potential (MEP) properties. Prediction of activity spectra for substances (PASS) indicated promising antiviral, anti-carcinogenic, and antifungal functionality of these cytidine esters compared to the antibacterial activities. To support this observation, their cytotoxic prediction and molecular docking studies have been performed against HIV-1 reverse transcriptase (RT) (PDB: 3V4I). Most of the molecules studied out here could bind near the crucial catalytic binding site, Tyr181, Ile94, Ile382, Lys374, Val381, Val90, and Tyr34 of the HIV-1 reverse transcriptase (RT), and the molecules were surrounded by other active site residues like Gln332, Trp406, Asn265, Gly93, His96, Pro95, and Thr165. Finally, these novel molecules were analyzed for their pharmacokinetic properties which expressed that the combination of in silico ADMET prediction, toxicity prediction, and drug-likeness had shown a promising result. The study discusses the performance of molecular docking to suggest the novel molecules active against resistance mutants of RT and/or recombinant strains of HIV-1.

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.

2,4-Dichloro-5-[(N-aryl/alkyl)sulfamoyl]benzoic Acid Derivatives: In Vitro Antidiabetic Activity, Molecular Modeling and In silico ADMET Screening

2019 ◽  
Vol 15 (2) ◽  
pp. 186-195 ◽  
Author(s):  
Samridhi Thakral ◽  
Vikramjeet Singh
Keyword(s):  
Molecular Docking ◽  
Benzoic Acid ◽  
Inhibitory Activity ◽  
In Silico ◽  
Computational Study ◽  
Antidiabetic Activity ◽  
Standard Drug ◽  
Benzoic Acid Derivatives ◽  
In Silico Admet ◽  
Inhibitory Potential

Background: Postprandial hyperglycemia can be reduced by inhibiting major carbohydrate hydrolyzing enzymes, such as α-glucosidase and α-amylase which is an effective approach in both preventing and treating diabetes. Objective: The aim of this study was to synthesize a series of 2,4-dichloro-5-[(N-aryl/alkyl)sulfamoyl] benzoic acid derivatives and evaluate α-glucosidase and α-amylase inhibitory activity along with molecular docking and in silico ADMET property analysis. Method: Chlorosulfonation of 2,4-dichloro benzoic acid followed by reaction with corresponding anilines/amines yielded 2,4-dichloro-5-[(N-aryl/alkyl)sulfamoyl]benzoic acid derivatives. For evaluating their antidiabetic potential α-glucosidase and α-amylase inhibitory assays were carried out. In silico molecular docking studies of these compounds were performed with respect to these enzymes and a computational study was also carried out to predict the drug-likeness and ADMET properties of the title compounds. Results: Compound 3c (2,4-dichloro-5-[(2-nitrophenyl)sulfamoyl]benzoic acid) was found to be highly active having 3 fold inhibitory potential against α-amylase and 5 times inhibitory activity against α-glucosidase in comparison to standard drug acarbose. Conclusion: Most of the synthesized compounds were highly potent or equipotent to standard drug acarbose for inhibitory potential against α-glucosidase and α-amylase enzyme and hence this may indicate their antidiabetic activity. The docking study revealed that these compounds interact with active site of enzyme through hydrogen bonding and different pi interactions.

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