Explore chapters and articles related to this topic
Approaches for Identification and Validation of Antimicrobial Compounds of Plant Origin: A Long Way from the Field to the Market
Published in Mahendra Rai, Chistiane M. Feitosa, Eco-Friendly Biobased Products Used in Microbial Diseases, 2022
Lívia Maria Batista Vilela, Carlos André dos Santos-Silva, Ricardo Salas Roldan-Filho, Pollyanna Michelle da Silva, Marx de Oliveira Lima, José Rafael da Silva Araújo, Wilson Dias de Oliveira, Suyane de Deus e Melo, Madson Allan de Luna Aragão, Thiago Henrique Napoleão, Patrícia Maria Guedes Paiva, Ana Christina Brasileiro-Vidal, Ana Maria Benko-Iseppon
To obtain a new drug or vaccine, several parameters must be analyzed. The screening of antiviral molecules has been one of the first steps in searching for molecules against SARS-CoV2. For this purpose, bioinformatics provides essential tools to speed up the identification of new molecules. Also, other in silico analysis work as parameters to determine the choice between the candidates. Some techniques are essential in this search, such as virtual screening, used in the search for candidates available in databases (mining), characterization of the primary structure through the prediction of physicochemical properties, antimicrobial activity, toxicological, allergenic and immunogenic potential. The evaluation of the tertiary structure performed through molecular modeling, refinement of the model obtained and the evaluation of its quality are essential steps to obtain the most representative model for the next stages of molecular simulation (Odhar et al. 2020; Santos-Silva et al. 2020).
Triterpenoids from Gymnema Sylvestre R.Br. (Periploca of the Woods): Biological Significance in the Treatment of Diabetes
Published in Megh R. Goyal, Preeti Birwal, Santosh K. Mishra, Phytochemicals and Medicinal Plants in Food Design, 2022
The use of bioinformatics resources namely databases information on diabetes, molecular modeling approaches, QSAR and softwares, have contributed in identification of novel “drug-like” molecules and the analysis of their pharmacokinetic properties (absorption, distribution, metabolism, excretion, and toxicity) [63, 64]. The study discussed the prediction of anti-diabetic activity of phytomolecules by QSAR model, a statistical approach in prediction of “drug-like” molecules. Molecular docking and ADMET analysis showed active Gymnemic acid analogs. However, poor bioavailability of molecules requires further optimization. The in silico screening methods provide an important tool to gain insights on the potential of natural “lead molecules” for drug designing in diabetes.
Granulation of Poorly Water-Soluble Drugs
Published in Dilip M. Parikh, Handbook of Pharmaceutical Granulation Technology, 2021
Albert W. Brzeczko, Firas El Saleh, Hibreniguss Terefe
Over the past several decades, advances in drug discovery techniques have been significant in identifying new and novel therapeutics agents in the pharmaceutical industry. Receptor mapping and molecular modeling coupled with high-throughput screening have revealed a plethora of drug candidates for numerous disease states. Because of the nature and the location of many of these receptors in a lipophilic membrane, drug candidates having the best molecular configuration and fitting into these receptors may, by design, be poorly water-soluble. It is estimated that 90% of new chemical entities in drug development are characterized as poorly water-soluble with a potential market impact projected at $145 billion [1]. Crestor® (rosuvastatin calcium), Nexium® (esomeprazole magnesium), and Sovaldi® (sofosbuvir) are drugs with significant therapeutic impact, which are classified as poorly water-soluble. This rise of more poorly water-soluble drug candidates in development presents a challenge to formulators of pharmaceutical oral solid dosage forms to improve the drug’s bioavailability while maintaining product stability, both physically and chemically, as well as providing a robust commercial process.
Molecular docking studies, anti-Alzheimer’s disease, antidiabetic, and anti-acute myeloid leukemia potentials of narcissoside
Published in Archives of Physiology and Biochemistry, 2023
Tingting Liu, Lixia Cao, Tingting Zhang, Huan Fu
Firstly, it was used from Gaussian software program (Frisch et al.2009) to obtain optimised structures of molecules, which created files with *.sdf extension using these structures. Using these files, all calculations were made with Maestro Molecular modelling platform (version 12.2) by Schrödinger, LLC (2019a). Maestro Molecular modelling platform (version 12.2) by Schrödinger comes together from many modules. In the first module used, the protein preparation module (Friesner et al.2006, Schrödinger 2019b) was used for the preparation of proteins. There are many small proteins in the enzymes studied. The crystal structures of these proteins have been downloaded from the protein data bank site. These enzymes were initially minimised and the water molecules in the structure were removed. In the next step, the active sites of the enzymes were determined, in which the proteins in this active zone were given freedom of movement. Therefore, these proteins were enabled to interact with molecules more easily. In the next step, the molecule was prepared for calculations, the LigPrep module (Sastry et al.2013, Schrödinger 2019c) was used for this process.
Design and synthesis of novel quinazolinone-based derivatives as EGFR inhibitors with antitumor activity
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Amr Sonousi, Rasha A. Hassan, Eman O. Osman, Amr M. Abdou, Soha H. Emam
The crystallographic structure of EGFR protein (PDB: 1M17) was obtained from the protein data bank website, (http://www.pdb.org) with resolution of 2.60 Å. All the molecular modelling studies were carried out using Molecular Operating Environment (MOE 2020.09; Chemical Computing Group, Canada) as the computational software. The hydrogen atoms were added, the protonation states of the amino acid residues were assigned, and the partial charges of atoms were added using Protonate 3D algorithm. Compounds were modelled using MOE builder, and the structure was energy minimised using the MMFF94x force field. Using the MOE induced-fit Dock tool, docking studies of the synthesised compound into the active site was done and the final docked complexes of ligand–enzyme was selected according to the criteria of binding energy score combined with geometrical matching quality.
Formulation of amorphous ternary solid dispersions of dapagliflozin using PEG 6000 and Poloxamer 188: solid-state characterization, ex vivo study, and molecular simulation assessment
Published in Drug Development and Industrial Pharmacy, 2020
Nabil K. Alruwaili, Ameeduzzafar Zafar, Syed Sarim Imam, Khalid Saad Alharbi, Sultan Alshehri, Tilal Elsaman, Fadhel Ahmed Alomar, Sultan Akhtar, Usama A. Fahmy, Nabil A. Alhakamy, Mohammed Salem Alshammari
Molecular modeling has been used extensively to assist in understanding experimental data and to predict the atomic and molecular properties that can provide guidance for experiment design. In the current study, the computation of binding strength between the drug and carrier was carried out with molecular modeling approach. The drug–polymer interaction patterns were identified by placing the drug molecule within the proximity of the dimer and then energy optimized to a local energy minimum [32,33]. The chemical structures of the DFG were in silico generated using ACD/Chem Sketch freeware (2D and 3D) and then saved in PDB format for docking studies. The 2D structures of the polymers (PEG and PLX) were drawn, conformationally optimized using ACD/Chem Sketch Freeware and converted to PDB format using Open Babel module. It was energetically minimized by Spdbv (4.1.0.) [34]. Auto-Dock 4.2 was used to convert the pdb file format to pdbqt, and a grid box size of 80 × 80 × 80 points in x, y, and z directions with points was separated by 0.375 Å. The Lamarckian genetic algorithm methodology was used for docking simulations by Auto Dock 4.2. Auto Dock Tools 1.5.6 [35]. The docking results were analyzed and visualized for hydrogen bonding and calculation was done using the Discovery studio visualizer (Accelrys Software Inc., 2007 Accelrys Discovery Studio Visualiser v 2.5.5, Accelrys Software Inc., San Diego, CA).