Exploring biological efficacy of novel benzothiazole linked 2,5-disubstituted-1,3,4-oxadiazole hybrids as efficient α-amylase inhibitors: Synthesis, characterization, inhibition, molecular docking, molecular dynamics and Monte Carlo based QSAR studies

Background: Rapid evolution of drug resistance and side effects of currently used drugs develop more efficacious and newer antimicrobial agents. Further, for the management of Type II Diabetes, α-gulcosidase and α-amylase inhibitors play a very important role by inhibiting the postprandial hyperglycemia. Objectives: The objective of this study was to synthesize N-aryl/N,N-dimethyl sulphonamides, investigate their antihyperglycemic and antimicrobial potential, develop QSAR model for identifying molecular descriptors and predict their binding modes and in silico ADMET properties. Methods: Synthesized derivatives were subjected to in vitro studies for their antidiabetic activity against α-glucosidase and α-amylase enzymes and antimicrobial activity. Molecular docking studies were carried out to find out molecular binding interactions of the ligand molecules with their respective targets. QSAR studies were carried out to identify structural determinants responsible for antimicrobial activity. Results: Antidiabetic study demonstrated the potent activity of two compounds 2 and 6 as α- glucosidase and α-amylase inhibitors, as well as compound 1 and 2, exhibited potent antimicrobial activity against all the tested microbes. All the compounds have more antifungal potential against Candida albicans. QSAR studies confirmed the role of molecular connectivity indices (valence first order and second order) in controlling the antimicrobial activity. Molecular docking studies supported the observed in vitro biological activities of the synthesized compounds. Conclusion: The compounds with 2,3-dimethyl substitution were found to be antidiabetic agents and molecules having bromo and 2,3-dimethyl substituents on phenyl ring have established themselves as potent antimicrobial agents. The role of valence first and 2nd order molecular connectivity indices as molecular properties were identified for antimicrobial activity and various electrostatic, hydrogen bonding and hydrophobic interactions were found to be prominent in the binding of molecules at the target site.

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Molecular Docking and Molecular Dynamics Simulation Based Approach to Explore the Dual Inhibitor Against HIV-1 Reverse Transcriptase and Integrase

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207320666170615104703 ◽

2017 ◽

Vol 20 (8) ◽

Cited By ~ 11

Author(s):

Subhash Chander ◽

Rajan Kumar Pandey ◽

Ashok Penta ◽

Bhanwar Singh Choudhary ◽

Manish Sharma ◽

...

Keyword(s):

Molecular Dynamics ◽

Molecular Docking ◽

Molecular Dynamics Simulation ◽

Reverse Transcriptase ◽

Dynamics Simulation ◽

Dual Inhibitor ◽

Simulation Based ◽

Hiv 1

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The Application of the Combination of Monte Carlo Optimization Method based QSAR Modeling and Molecular Docking in Drug Design and Development

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557520666200212111428 ◽

2020 ◽

Vol 20 (14) ◽

pp. 1389-1402 ◽

Cited By ~ 1

Author(s):

Maja Zivkovic ◽

Marko Zlatanovic ◽

Nevena Zlatanovic ◽

Mladjan Golubović ◽

Aleksandar M. Veselinović

Keyword(s):

Monte Carlo ◽

Molecular Docking ◽

Computer Calculation ◽

Molecular Graph ◽

Optimization Method ◽

Docking Studies ◽

Optimization Approach ◽

Qsar Modeling ◽

Monte Carlo Optimization ◽

Molecular Docking Studies

In recent years, one of the promising approaches in the QSAR modeling Monte Carlo optimization approach as conformation independent method, has emerged. Monte Carlo optimization has proven to be a valuable tool in chemoinformatics, and this review presents its application in drug discovery and design. In this review, the basic principles and important features of these methods are discussed as well as the advantages of conformation independent optimal descriptors developed from the molecular graph and the Simplified Molecular Input Line Entry System (SMILES) notation compared to commonly used descriptors in QSAR modeling. This review presents the summary of obtained results from Monte Carlo optimization-based QSAR modeling with the further addition of molecular docking studies applied for various pharmacologically important endpoints. SMILES notation based optimal descriptors, defined as molecular fragments, identified as main contributors to the increase/ decrease of biological activity, which are used further to design compounds with targeted activity based on computer calculation, are presented. In this mini-review, research papers in which molecular docking was applied as an additional method to design molecules to validate their activity further, are summarized. These papers present a very good correlation among results obtained from Monte Carlo optimization modeling and molecular docking studies.

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Design of potential IKK-β inhibitors using molecular docking and molecular dynamics techniques for their anti-cancer potential

Current Computer - Aided Drug Design ◽

10.2174/1573409916666200102121505 ◽

2020 ◽

Vol 16 ◽

Author(s):

Salam Pradeep Singh ◽

Iftikar Hussain ◽

Bolin Kumar Konwar ◽

Ramesh Chandra Deka ◽

Chingakham Brajakishor Singh

Keyword(s):

Molecular Dynamics ◽

Molecular Docking ◽

Md Simulation ◽

Inflammatory Diseases ◽

Binding Free Energy ◽

Anti Cancer ◽

Dietary Phytochemicals ◽

Toxicity Analysis ◽

The Stability ◽

Stable Trajectory

Aim and Objective: To evaluate a set of seventy phytochemicals for their potential ability to bind the inhibitor of nuclear factor kappaB kinase beta (IKK-β) which is a prime target for cancer and inflammatory diseases. Materials and Methods: Seventy phytochemicals were screened against IKK-β enzyme using DFT-based molecular docking technique and the top docking hits were carried forward for molecular dynamics (MD) simulation protocols. The adme-toxicity analysis was also carried out for the top docking hits. Results: Sesamin, matairesinol and resveratrol were found to be the top docking hits with a total score of -413 kJ/mol, -398.11 kJ/mol and 266.73 kJ/mol respectively. Glu100 and Gly102 were found to be the most common interacting residues. The result from MD simulation observed a stable trajectory with a binding free energy of -107.62 kJ/mol for matairesinol, -120.37 kJ/mol for sesamin and -40.56 kJ/mol for resveratrol. The DFT calculation revealed the stability of the compounds. The ADME-Toxicity prediction observed that these compounds fall within the permissible area of Boiled-Egg and it does not violate any rule for pharmacological criteria, drug-likeness etc. Conclusion: The study interprets that dietary phytochemicals are potent inhibitors of IKK-β enzyme with favourable binding affinity and less toxic effects. In fact, there is a gradual rise in the use of plant-derived molecules because of its lesser side effects compared to chemotherapy. The study has also provided an insight by which the phytochemicals inhibited the IKK-β enzyme. The investigation would also provide in understanding the inhibitory mode of certain dietary phytochemicals in treating cancer.

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