Virtual Screening, Molecular Docking and QSAR Studies in Drug Discovery and Development Programme

Structure-based drug design (SBDD) and ligand-based drug design (LBDD) are the two basic approaches of computer-aided drug design (CADD) used in modern drug discovery and development programme. Virtual screening (or in silico screening) has been used in drug discovery program as a complementary tool to high throughput screening (HTS) to identify bioactive compounds. It is a preliminary tool of CADD that has gained considerable interest in the pharmaceutical research as a productive and cost-effective technology in search for novel molecules of medicinal interest. Docking is also used for virtual screening of new ligands on the basis of biological structures for identification of hits and generation of leads or optimization (potency/ property) of leads in drug discovery program. Hence, docking is approach of SBDD which plays an important role in rational designing of new drug molecules. Quantitative structure-activity relationship (QSAR) is an important chemometric tool in computational drug design. It is a common practice of LBDD. The study of QSAR gives information related to structural features and/or physicochemical properties of structurally similar molecules to their biological activity. In this paper, a comprehensive review on several computational tools of SBDD and LBDD such as virtual screening, molecular docking and QSAR methods of and their applications in the drug discovery and development programme have been summarized. Keywords: Virtual screening, Molecular docking, QSAR, Drug discovery, Lead molecul

Echinoderms Metabolites: Structure, Functions and Biomedical Perspectives

The materials published in the Special Issue reflect the real diversity of echinoderm metabolites and cover most of their specific classes and biomedical potential as antioxidant, antiviral, anticancer, and even anticoagulant preparations. The metabolites include sea urchin naphtoquinoid pigments and their semi-synthetic derivatives, sea cucumber triterpene glycosides, esters of polyhydroxysteroids from starfish, sea urchins free sterols, and sea cucumber fucosylated chondroitin sulfates. This Special Issue, “Echinoderm Metabolites: Structure, Functions, and Biomedical Perspectives”, is a collection of articles about different scientific aspects concerning low molecular weight and biopolymer metabolites from echinoderms, including their isolation and chemical structures, biological activities, biosynthesis and evolution, biological functions, and obtaining of semi-synthetic derivatives of biologically active natural products. This Special Issue includes materials about sea urchin naphtoquinoid pigments and their semi-synthetic derivatives, sea cucumber triterpene glycosides, esters of polyhydroxysteroids from starfish, sea urchin free sterols, and sea cucumber fucosylated chondroitin sulfates

pdCSM-cancer: Using Graph-Based Signatures to Identify Small Molecules with Anticancer Properties.

The development of new, effective, and safe drugs to treat cancer remains a challenging and time-consuming task due to limited hit rates, restraining subsequent development efforts. Despite the impressive progress of quantitative structure-activity relationship and machine learning-based models that have been developed to predict molecule pharmacodynamics and bioactivity, they have had mixed success at identifying compounds with anticancer properties against multiple cell lines. Here, we have developed a novel predictive tool, pdCSM-cancer, which uses a graph-based signature representation of the chemical structure of a small molecule in order to accurately predict molecules likely to be active against one or multiple cancer cell lines. pdCSM-cancer represents the most comprehensive anticancer bioactivity prediction platform developed till date, comprising trained and validated models on experimental data of the growth inhibition concentration (GI50%) effects, including over 18,000 compounds, on 9 tumor types and 74 distinct cancer cell lines. Across 10-fold cross-validation, it achieved Pearson's correlation coefficients of up to 0.74 and comparable performance of up to 0.67 across independent, non-redundant blind tests. Leveraging the insights from these cell line-specific models, we developed a generic predictive model to identify molecules active in at least 60 cell lines. Our final model achieved an area under the receiver operating characteristic curve (AUC) of up to 0.94 on 10-fold cross-validation and up to 0.94 on independent non-redundant blind tests, outperforming alternative approaches. We believe that our predictive tool will provide a valuable resource to optimizing and enriching screening libraries for the identification of effective and safe anticancer molecules. To provide a simple and integrated platform to rapidly screen for potential biologically active molecules with favorable anticancer properties, we made pdCSM-cancer freely available online at http://biosig.unimelb.edu.au/pdcsm_cancer

Bioinformatics Analysis and Modelling of Therapeutically Relevant Molecules

Ph.DDOCTOR OF PHILOSOPH

Heterocyclic Compounds from Marine Organisms

Marine drugs have drawn considerable attention due to their significant biological and pharmacological properties, such as antimicrobial or antibacterial activities and antitumor effects, among others. The frequent occurrence of heterocyclic motifs in the structure of many of these targets has revealed the key role of these units as promising pharmacophores. In this Special Issue we have gathered several original papers which highlight the isolation, structural elucidation and biological essays of newly isolated heterocyclic marine drugs, as well as reviews which give an overview of the isolation, synthesis and pharmacological activities of different classes of marine heterocycles

Anticancer Agents

This book is a printed edition of the Special Issue entitled “Anticancer Agents: Design, Synthesis and Evaluation” that was published in Molecules. Two review articles and thirty research papers are included in the Special Issue. Three second-generation androgen receptor antagonists that have been approved by the U.S. FDA for the treatment of prostate cancer have been reviewed. Identification of mimics of protein partners as protein-protein interaction inhibitors via virtual screening has been summarized and discussed. Anticancer agents targeting various protein targets, including IGF-1R, Src, protein kinase, aromatase, HDAC, PARP, Toll-Like receptor, c-Met, PI3Kdelta, topoisomerase II, p53, and indoleamine 2,3-dioxygenase, have been explored. The analogs of three well-known tubulin-interacting natural products, paclitaxel, zampanolide, and colchicine, have been designed, synthesized, and evaluated. Several anticancer agents representing diverse chemical scaffolds were assessed in different kinds of cancer cell models. The capability of some anticancer agents to overcome the resistance to currently available drugs was also studied. In addition to looking into the in vitro ability of the anticancer agents to inhibit cancer cell proliferation, apoptosis, and cell cycle, in vivo antitumor efficacy in animal models and DFT were also investigated in some papers