In silico approaches in the study of traditional Chinese herbal medicine

Ph.DDOCTOR OF PHILOSOPH

Pharmacogenetic modeling of human cytochrome P450 2D6; On the force of variation in inducing toxicity

Understanding the way in which drugs are metabolized by CYP2D6 and hence the underlying mechanisms that define potential toxicity is crucial to avoid adverse reactions. The high occurrence of CYP2D6 polymorphs enhances the complexity of the toxicity assessment of a drug candidate and should be tackled from early drug discovery phase on. The research described in this PhD thesis has been performed to provide novel fundamental insights regarding the metabolic activity of CYP2D6 wild-type and several polymorphs using various state-of-the-art in silico techniques. The results of the CYP2D6-focused studies enhance our knowledge regarding the enzyme particularities, and can be used to accelerate the development of CYP2D6 modeling tools with more accurate and reliable predictions

In Silico Strategies for Prospective Drug Repositionings

The discovery of new drugs is one of pharmaceutical research's most exciting and challenging tasks. Unfortunately, the conventional drug discovery procedure is chronophagous and seldom successful; furthermore, new drugs are needed to address our clinical challenges (e.g., new antibiotics, new anticancer drugs, new antivirals).Within this framework, drug repositioning—finding new pharmacodynamic properties for already approved drugs—becomes a worthy drug discovery strategy.Recent drug discovery techniques combine traditional tools with in silico strategies to identify previously unaccounted properties for drugs already in use. Indeed, big data exploration techniques capitalize on the ever-growing knowledge of drugs' structural and physicochemical properties, drug–target and drug–drug interactions, advances in human biochemistry, and the latest molecular and cellular biology discoveries.Following this new and exciting trend, this book is a collection of papers introducing innovative computational methods to identify potential candidates for drug repositioning. Thus, the papers in the Special Issue In Silico Strategies for Prospective Drug Repositionings introduce a wide array of in silico strategies such as complex network analysis, big data, machine learning, molecular docking, molecular dynamics simulation, and QSAR; these strategies target diverse diseases and medical conditions: COVID-19 and post-COVID-19 pulmonary fibrosis, non-small lung cancer, multiple sclerosis, toxoplasmosis, psychiatric disorders, or skin conditions

Molecular Science for Drug Development and Biomedicine

With the avalanche of biological sequences generated in the postgenomic age, molecular science is facing an unprecedented challenge, i.e., how to timely utilize the huge amount of data to benefit human beings. Stimulated by such a challenge, a rapid development has taken place in molecular science, particularly in the areas associated with drug development and biomedicine, both experimental and theoretical. The current thematic issue was launched with the focus on the topic of “Molecular Science for Drug Development and Biomedicine”, in hopes to further stimulate more useful techniques and findings from various approaches of molecular science for drug development and biomedicine

Plant extracts and natural products - Predictive structural and biodiversity-based analyses of uses, bioactivity, and 'research and development' potential

The process of drug discovery and development over the last 30 years has been increasingly shaped by formulaic approaches and natural products – integral to the drug discovery process and widely recognized as the most successful class of drug leads – have significantly been deprioritized by a struggling worldwide pharmaceutical industry. Alkaloids - historically the most important superclass of medically important secondary metabolites - have been used worldwide as a source of remedies to treat a wide variety of illnesses yet, there exists a wide discrepancy between their historical and modern significances. To understand these trends from an insider’s perspective, 52 senior-stakeholders in industry and academia were engaged to provide insights on a series of qualitative and quantitative aspects related to developments in the process of drug discovery from natural products. Stakeholders highlighted the dissonance between the perceived high potential of natural products as drug leads and overall industry and company level strategies. Many industry contacts were highly critical to prevalent company and industry-wide drug discovery strategies indicating a high level of dissatisfaction within the industry. One promising strategy which respondents highlighted was virtual screening which, to a large extent has not been explored in natural products research strategies. Furthermore, the physicochemical features of 27,783 alkaloids from the Dictionary of Natural Products were cross-referenced to pharmacologically significant and other metrics from various databases including the European Bioinformatics Institute’s ChEMBL and Global Biodiversity Information Facility’s GBIF biodiversity data. The combined dataset revealed that a compound's likelihood of medicinal use can be linked to its host species’ abundance and was input into target-independent machine learning algorithms to predict likelihood of pharmaceutical use. The neural network model demonstrated an accuracy of >57% for all pharmaceutical alkaloids and 98% of all alkaloids. This study is the first to incorporate the biodiversity of host organisms in a machine learning scheme characterizing druglikeness and thus demonstrates the link between host species’ abundance and druglikeness. These findings yield new insights into cost-effective, real-world indicators of drug development potential across the diverse field of natural products

Brain-Targeted Drug Delivery

Brain diseases currently affect one in six people worldwide; they include a wide range of neurological diseases, from Alzheimer’s and Parkinson’s diseases to epilepsy, brain injuries, brain cancer, neuroinfections, and strokes. The treatment of these diseases is complex and limited due to the presence of the blood–brain barrier (BBB), which covers the entirety of the brain. The BBB not only has the function of protecting the brain from harmful substances; it is also a metabolic barrier and a transport regulator of nutrients/serum factors/neurotoxins. Knowing these characteristics when it comes to the treatment of brain diseases makes it easier to understand the lack of efficacy of therapeutic drugs, resulting from the innate resistance of the BBB to permeation. To overcome this limitation, drug delivery systems based on nanotechnology/microtechnology have been developed. Brain-targeted drug delivery enables targeted therapy with a higher therapeutic efficacy and fewer side effects because it targets moieties present in the drug delivery systems

Advances in Ginsenosides

This book collected recent innovative research and review articles on analytical techniques, production protocols, biotechnological tools, and new insights into bioactivities of ginsenosides including the effects on epithelial-mesenchymal transition, hippocampal neurogenesis and inflammation as well as on diseases such as ischemic stroke, autoimmune diseases, and allergic disorders. Additionally, the analysis through molecular docking and an overview of the Panax ginseng pharmacopuncture were also presented

Brain Injury

The present two volume book "Brain Injury" is distinctive in its presentation and includes a wealth of updated information on many aspects in the field of brain injury. The Book is devoted to the pathogenesis of brain injury, concepts in cerebral blood flow and metabolism, investigative approaches and monitoring of brain injured, different protective mechanisms and recovery and management approach to these individuals, functional and endocrine aspects of brain injuries, approaches to rehabilitation of brain injured and preventive aspects of traumatic brain injuries. The collective contribution from experts in brain injury research area would be successfully conveyed to the readers and readers will find this book to be a valuable guide to further develop their understanding about brain injury

RECENT ADVANCES IN MOLECULAR MEDICINE AND TRANSLATIONAL RESEARCH

ABSTRACT BOO

Database development and machine learning classification of medicinal chemicals and biomolecules

Ph.DDOCTOR OF PHILOSOPH