Ligand Based Pharmacophore Modelling, Virtual Screening, Molecular Docking, and ADMETOX of Natural Compounds as Antibiotic Candidates against Urinary Tract Infections (UTI)

The use of antibiotic drugs requires close supervision that patients take antibiotics according to the rules. Irregular antibiotic use led to increased ADR cases (Antibiotic Drug-resistant). ADR is when an individual becomes resistant to an antibiotic drug that cannot kill bacteria. The high number of ADR cases prompted drug discovery to be implemented in analysis for Antibiotic candidates with good effectiveness through the Molecular Docking approach. The search for candidate test compounds as antibiotics were performed using the pharmacophore modelling method and molecular docking. And piperine, withaferin, has some of the same amino acids Ala101, Val103, Glu166, Trp165, and Leu102. Based on the prediction of the promising potential test ligand compound is Corosolic acid. In addition to assessing drug-likeness, pharmacokinetic and toxicity parameters, corosolic acid also has the lowest binding energy among other compounds. Through a textual bioinformatics approach, molecular docking simulations can be used as a first step in the search for new drug candidates in silico by considering various aspects, starting from the physicochemical properties of protein-ligand compounds and the environment. Analysis during the docking process to ADMETOX is an analysis to see the effectiveness and in silico compound safety. 

IN SILICO METHODS FOR DRUG DESIGN AND DISCOVERY

Computer-aided drug design (CADD) methodologies are playing an ever-increasing role in drug discovery that are critical in the cost-effective identification of promising drug candidates. These computational methods are relevant in limiting the use of animal models in pharmacological research, for aiding the rational design of novel and safe drug candidates, and for repositioning marketed drugs, supporting medicinal chemists and pharmacologists during the drug discovery trajectory.Within this field of research, we launched a Research Topic in Frontiers in Chemistry in March 2019 entitled “In silico Methods for Drug Design and Discovery,” which involved two sections of the journal: Medicinal and Pharmaceutical Chemistry and Theoretical and Computational Chemistry. For the reasons mentioned, this Research Topic attracted the attention of scientists and received a large number of submitted manuscripts. Among them 27 Original Research articles, five Review articles, and two Perspective articles have been published within the Research Topic. The Original Research articles cover most of the topics in CADD, reporting advanced in silico methods in drug discovery, while the Review articles offer a point of view of some computer-driven techniques applied to drug research. Finally, the Perspective articles provide a vision of specific computational approaches with an outlook in the modern era of CADD

Virtual Screening of Multi-Target Agents by Combinatorial Machine Learning Methods

Ph.DDOCTOR OF PHILOSOPH

Computational Approaches: Drug Discovery and Design in Medicinal Chemistry and Bioinformatics

This book is a collection of original research articles in the field of computer-aided drug design. It reports the use of current and validated computational approaches applied to drug discovery as well as the development of new computational tools to identify new and more potent drugs

Chemical Information Bulletin

Periodic supplement for "the regular journals of the American Chemical Society," containing annotated bibliographies of chemical documentation literature as well as information about meetings, conferences, awards, scholarships, and other news from the American Chemical Society (ACS) Division of Chemical Literature

DESIGN, SYNTHESIS AND BIOLOGICAL EVALUATION OF NOVEL SELECTIVE CANNABINOID RECEPTOR 2 (CB2) LIGANDS WITH THERAPEUTIC POTENTIALS

Cannabinoid receptors 1 and 2 (CB1 and CB2) belong to the rhodopsin-like family of the G-Protein Coupled Receptors (GPCRs). CB1 receptors are highly expressed in the central nervous system, while CB2 receptors are expressed mainly in the immune cells and the periphery. Targeting the CB2 receptors is believed to avoid the psychoactive side effects associated with CB1 receptors. CB2 receptors have been shown to be involved in several physiological functions as well as diseases, such as pain, multiple sclerosis, osteoporosis, and cancer demonstrating the importance of the CB2 receptors. In the present study, we employed chemistry design and discovery to identify novel CB2 ligands, carried out in-vitro functional studies, and evaluated the therapeutic potentials. Several chemical scaffolds were discovered and evaluated. The di-amide scaffold was discovered utilizing pharmacophore drug discovery and molecular docking studies. Several derivatives of the di-amide scaffold demonstrated potent and highly selective CB2 inverse agonists as well as potent anti-osteoclast formation capabilities. The di-amide derivatives suffered from weak anti-multiple myeloma (MM) properties and poor pharmacokinetic properties. A new scaffold was identified utilizing scaffold hopping and molecular docking studies. However, the 2-(sulfonylamino)-2-phenylacetamide scaffold demonstrated weak CB2 binding affinity. Due to the limitation of the two previous scaffolds, virtual high-throughput screening as well as structure-based drug design were utilized for scaffold hopping in order to identify new CB2 scaffolds. A new lead compound was identified and structure activity relationship (SAR) studies were conducted on the scaffold 4-(aminomethyl)-N,N-diethylaniline. Several novel compounds were discovered with high potency and selectivity. Functional experiments showed different functionality (agonist and inverse agonist) of these compounds. Nevertheless, therapeutic studies showed that inverse agonism is essential for the OCL inhibition effects while anti-MM experiments showed that CB2 agonists are more effective than inverse agonists