18^th International Conference on Medicinal Chemistry & Targeted Drug Delivery December 06-08, 2017 Dallas, USA

Plant research and its  technologies have improved dramatically over the last 5 years as a result of the revolutionary breakthroughs including new gene editing technologies and reduction in the cost of sequencing. Many plants have now been successfully sequenced and a wide range of biological data sets made available. As a result, plant scientists are now more than ever making use of state of the art technology platforms to help explain biological principals, advance research and therefore enable benefits such as crop improvement / breeding etc. The goals of agricultural plant science are to increase crop productivity, increase the quality of agricultural products, and maintain the environment. The success of transgenic crops has erased the last vestiges of doubt about the value of agricultural biotechnology and triggered large-scale investments in plant genomics. Genetic maps are also an important resource for plant gene isolation, as once the genetic position of any mutation. Since the invention of plant cell and tissue culture techniques more than half a century ago, scientists have been trying to understand the morphological, physiological, biochemical and molecular changes associated with tissue culture responses. Establishment of de novo developmental cell fate in vitro is governed by factors such as genetic make-up, stress and plant growth regulators.
 

Perhaps nothing epitomizes the fusion of traditional and biomedicine more than predictive, preventive and personalized and participatory medicine. The truth is that modern medicine is desperately short of new treatments. It takes years for a new drug to get through the research and development pipeline to manufacture and the cost is enormous. Estimates suggest up to 80 per cent of the population has tried a therapy such as acupuncture or homeopathy. and a survey conducted earlier this year found that 74 per cent of us medical students believe that western medicine would benefit by integrating traditional or alternative therapies and practices.  Example –artemisinin , which is extracted from artemisia annua or chinese sweet wormwood, is the basis for the most effective malaria drugs the world has ever seen. But making traditional medicine truly mainstream — incorporating its knowledge into modern healthcare and ensuring it meets modern safety and efficacy standards — is no easy task and is far from complete.
 

The term “nutraceutical” is used to describe these medicinally or nutritionally functional foods. Nutraceuticals, which have also been called medical foods, designer foods, phytochemicals, functional foods and nutritional supplements, include such everyday products as “bio” yoghurts and fortified breakfast cereals, as well as vitamins, herbal remedies and even genetically modified foods and supplements. Both can have a similar effect on the body but the long term affect is devastatingly different. The idea is that, “we can produce the same type of effect as drugs without all of the side effects”. Nutraceuticals, in contrast to pharmaceuticals, are substances, which usually have not patent protection. The straightforward application of pharmaceutical standards, especially across national borders, is likely to be a difficult challenge and could effectively paralyze the industry. We are all advocates for all natural nutrition, but due to the legal claim that only drugs can cure, prevent or mitigate. Nutraceuticals   cannot be recommended by doctors when someone is suffering from illness.
 

Chemistry is a stimulating field as it links many scientific disciplines and allows for collaboration with other scientists in researching and developing new drugs.

Chemists apply their chemistry training to the process of synthesizing new pharmaceuticals. They also improve the processes by which existing pharmaceuticals are made. Medicinal chemists are focused on drug discovery and development and are concerned with the isolation of medicinal agents found in plants, as well as the creation of new synthetic drug compounds. Most chemists work with a team of scientists from different disciplines, including biologists, toxicologists, pharmacologists, theoretical chemists, microbiologists, and biopharmacists. Together, this team uses sophisticated analytical techniques to synthesize and test new drug products and to develop the most cost-effective and environmentally friendly means of production.Human exposure to contemporary materials and products has increased dramatically in modern times. We are constantly confronted with manufactured materials, both at work and during leisure pursuits, indoors as well as outdoors, whilst undertaking sports activities, or in social or educational environments. It is urgent to develop new therapeutic methods, with higher efficiency and lower side effects. Antimicrobial peptides (AMPs) are found in the innate immune system of a wide range of organisms. Identified as the most promising alternative to conventional molecules used nowadays against infections, some of them have been shown to have dual activity, both as antimicrobial and anticancer peptides (ACPs). Cereals such as wheat, rice, barley, rye, and maize have been recently identified as new sources of bioactive peptides. High quality cereal proteins are an important source of bioactive peptides, which consist of distinctive amino acid sequences, and which, once they are released, could display diverse functionalities.

Fast expansion in this area has been made possible by advances in software and hardware computational power and sophistication, identification of molecular targets, and an increasing database of publicly available target protein structures. CADD is being utilized to identify hits (active drug candidates), select leads (most likely candidates for further evaluation), and optimize leads i.e. transform biologically active compounds into suitable drugs by improving their physicochemical, pharmaceutical, ADMET /pk (pharmacokinetic) properties. Success of computer aided drug designing depends on the accuracy of modeled structure, accuracy of tools used for predicting binding site, performance of docking algorithms, correctness in mapping the pharmacophore, accuracy of energy minimization and simulation algorithms, reliability of adme and toxicity prediction tools as well as on synthetic feasibility of designed inhibitor or drug. QSAR and ADMET models, previous efforts made in drug discovery, success/failure, clinical trial data, efficacy and side-effects. Drug designing is an art, but the application of computer will play a major role in the attempts to make it more rational and successful in the future. Extensive use of computational approaches with higher accuracy could reduce the overall cost and failure of drug designing.We will address a number of pertinent topics including:

• The application of computational methods to the design of biologics
• Data analysis and visualization techniques to support multi-objective optimization
• The application of computational methods to drug discovery programs driven on data from phenotypic assays
• The impact of open source software and open data on drug design
• The impact of "big data" on drug discovery
• Computational methods applied to the optimization of binding kinetics

The basic premise of a TDDS is to concentrate the drug in the tissues of interest while reducing the relative concentration of medication in other remaining tissues. As a result, the drug is localized to a greater degree on the targeted site while leaving surrounding tissues unaffected. Platinum-based (pt-based) anticancer drugs have been recognized as one of the most effective drugs for clinical treatment of malignant tumors due to its unique mechanism of action and broad range of anticancer spectrum. TDDS has several advantages for the treatment of disease quantitatively. For instance, drug localization, decreased side effects, reduced dosage, modulated pharmacokinetics, controlled bio-distribution, and most importantly, improved patient's compliance. The main objective and basic principle behind the concept of targeting is that, the specific drug receptor is targeted to fit and improve their binding affinity, to the specific receptor that ultimately will trigger the pharmacological activity.
 

Medicinal chemistry is a stimulating field as it links many scientific disciplines and allows for collaboration with other scientists in researching and developing new drugs. . They also improve the processes by which existing pharmaceuticals are made. It deals with the facts of chemistry, pharmacoanalysis and the chemical analysis of compounds in the form of like small organic molecules such as insulin glargine, erythropoietin, and others. The four processes involved when a drug is taken are absorption, distribution, metabolism and elimination or excretion (ADME). Drugs interact and bind to the binding sites through intermolecular bonds (ionic, h-bonds, van der Waals, Dipole- Dipole hydrophobic). The process how drug distribute and reach its target (adme) and what will happen to the drug is pharmacokinetic. How the drugs interact with its target is known as pharmacodynamics.
 
 

The hyphenated technique is developed from the coupling of a separation technique and an on-line spectroscopic detection technology. Hyphenated techniques combine chromatographic and spectral methods to exploit the advantages of both. Chromatography produces pure or nearly pure fractions of chemical components in a mixture. Spectroscopy produces selective information for identification using standards or library spectra.  Hyphenated techniques have received ever-increasing attention as the principal means to solve complex analytical problems. Also called double hybrid e.g. –lc-pda-ms; lc-ms-ms; lc-nmr-ms instruments have become available and been applied to pharmaceutical problem solving. It gives faster and accurate analysis, high degree of automation, high sample throughput, separation and quantification achieved at the same time.  Applications include -quantitation of pollutants in drinking and waste water using official U.S. environmental protection agency methods. 2. Quantitation of drug in metabolites and urine is done for the pharmacological and forensic use. 3. Identification of unknown organic compounds in hazardous waste dumps and reaction products by synthetic organic chemistry. 4. Used for drug analysis, pesticide and herbicide detection.

Cancer is one of the most serious fatal diseases in today’s world that kills millions of people every year. It is one of the major health concerns of the 21st century which does not have any boundary and can affect any organ of people from any place. Nanoparticles are rapidly being developed and trialed to overcome several limitations of traditional drug delivery systems and are coming up as a distinct therapeutics for cancer treatment. It is a challenge to eradicate tumor cells while sparing normal cells. We used magneto electric nanoparticles (mens) to control drug delivery and release.  Current treatment strategies for cancer also include combination of radiation, chemotherapy and surgery. Important issues in this research include physical-chemical assembly of the nanocarriers, their surface interactions with biological media, cellular interactions, and controlled content release from the carriers. Several strategies have been used to address mdr, especially p-glycoprotein-mediated drug resistance in tumors.

 

Neurons are the building blocks of the nervous system which includes the brain and spinal cord. Neurons normally don’t reproduce or replace themselves, so when they become damaged or die they cannot be replaced by the body. Examples of neurodegenerative diseases include Parkinson’s, Alzheimer’s, and Huntington’s disease. Dementias are responsible for the greatest burden of neurodegenerative diseases, with Alzheimer’s representing approximately 60-70% of dementia cases. Many of these diseases are genetic. Sometimes the cause is a medical condition such as alcoholism, a tumor, or a stroke. Other causes may include toxins, chemicals, and viruses. Sometimes the cause is not known. Degenerative nerve diseases include Alzheimer’s disease, amyotrophic lateral sclerosis, fried Reich’s ataxia, Huntington’s disease, Parkinson’s disease, spinal muscular atrophy. Degenerative nerve diseases can be serious or life-threatening. It depends on the type. Most of them have no cure. Treatments may help improve symptoms, relieve pain, and increase mobility.

A worldwide increase in the rate of autism diagnoses—likely driven by broadened diagnostic criteria and increased awareness—has fueled concerns that an environmental exposure like vaccines might cause autism. Substantial data demonstrate immune abnormality in many autistic children consistent with impaired resistance to infection, activation of inflammatory response, and autoimmunity. T lymphocytes (t cells) are abnormal in many autistic children. Cytokines from t cells regulate the full spectrum of antibody and cell-mediated response, the latter being particularly important in resistance to viral infections. In autism, there is clear-cut evidence of activation of the immune response system, which may be due to innate, toxic, or infectious influences - or some combination of these factors.  Changes in certain genes increase the risk that a child will develop autism. If a parent carries one or more of these gene changes, they may get passed to a child (even if the parent does not have autism). Certain environmental influences may further increase – or reduce – autism risk in people who are genetically predisposed to the disorder.
 

These diseases include new infections, previously unrecognized infections and old infections reappearing due to antimicrobial resistance and public health issues due to unhygienic conditions. Infectious diseases are new and re-emerging infectious diseases that were once unknown or thought to be waning, along with recognition that drug resistance, hygiene, economic and environmental factors have promoted both reemergence and increased mortality. The global infectious diseases include AIDS, TB, malaria, influenza, and cholera. For an emerging disease to become established at least two events have to occur – (1) The infectious agent has to be introduced into a vulnerable population and (2) the agent has to have the ability to spread readily from person-to-person and cause disease. Influenza (or flu) is an example of an emerging disease that is due to both natural and human factors.  Zika virus in America which is associated with a birth defect known as microcephaly.   The Ebola virus epidemic that emerged in 2014 in West Africa illustrates how a virus that previously affected only small groups of people, perhaps a few hundred, can sweep rapidly through an area to affect tens of thousands, and become extremely difficult to contain.

 

Antibiotics are powerful medicines that fight bacterial infections. Most antibiotics fall into their individual antibiotic classes. An antibiotic class is a grouping of different drugs that have similar chemical and pharmacologic properties. Penicillins, tetracycline, cephalosporin, quinolones, lincomycins, macrolides, sulfonamides, aminoglycosides, carbapenems are few classes of antibiotics. Some antibiotics work by killing germs (bacteria or the parasite). This is often done by interfering with the structure of the cell wall of the bacterium or parasite. Some work by stopping bacteria or the parasite from multiplying. Most side-effects of antibiotics are not serious. Common side-effects include soft stools (faeces), diarrhoea, or mild stomach upset such as feeling sick (nausea). The overuse of antibiotics in recent years means they're becoming   less effective and has led to the emergence of "superbugs". These are strains of bacteria that have developed resistance to many different types of antibiotics

Personalized medicine (pm) has the potential to tailor therapy with the best response and highest safety margin to ensure better patient care. Sequencing of the human genome at the turn of the 21st century set in motion the transformation of personalized medicine from an idea to a practice. Pharmacogenomics” (pgx) – the study of variations of DNA and RNA characteristics as related to drug response – is a critically important area of personalized medicine where significant progress has recently been made. Personalized medicine’s greatest strides have been in cancer.  a targeted treatment targets a cancer’s specific genes and proteins that allow the cancer cells to grow and survive FDA determines that products are safe and effective before marketing through a careful evaluation of benefits and risks that considers the available scientific data in the context of the underlying condition or disease.
 

Microbes produce a wide range of molecules that can modulate eukaryotic immune responses. These agents interfere with the growth and reproduction of causative organisms like bacteria, fungi, parasites, virus etc. The journal of antimicrobial agents stocks up information about antibacterial, antifungal, antiviral, anti protozoal, anti-algal agents and their methods of detection, different therapies and advanced treatments to overcome diseases. These include factors that subvert protective mechanisms in order to facilitate pathogen colonization and persistence. Viral, bacterial and parasite-derived molecules have been identified that can inhibit inflammatory responses.  The indiscriminate use of conventional antibiotics has generated high rates of microbial resistance. Antimicrobial peptides (amps) constitute a promising alternative as therapeutic agents against various pathogenic microbes. These therapeutic agents can be isolated from different organisms, being widespread in nature and synthesized by microorganisms, plants and animals (both invertebrates and vertebrates). 

 

Zika virus (zikv) is an arbovirus belonging to the flaviviridae family. Vector-mediated transmission of zikv is initiated when a blood-feeding female aedes mosquito injects the virus into the skin of its mammalian host, followed by infection of permissive cells via specific receptors. Zikv contains a positive, single-stranded genomic RNA encoding a polyprotein that is processed into three structural proteins, i.e., the capsid (c), the precursor of membrane (prm), and the envelope (e), and seven nonstructural proteins, i.e., ns1 to ns5. Most individuals infected with zika virus experience mild or no symptoms. about 25% of infected people develop symptoms 2-10 days after infection, including rash, fever, joint pain, red eyes, and headache. There are currently no antiviral drugs or vaccines that can be used to treat or prevent infection with zika virus. We do have a safe and effective vaccine against another flavivirus, yellow fever virus. Mosquito control is the only option for restricting zika virus infection. Measures such as wearing clothes that cover much of the body, sleeping under a bed net, and making sure that breeding sites for mosquitoes (standing water in pots and used tires) are eliminated are examples.

 

Aurora kinases control multiple events during cell cycle progression and are essential for mitotic and meiotic bipolar spindle assembly and function. There are three aurora kinases in mammals, some of which have oncogenic properties and all of which are overexpressed in multiple cancers 2.The kinetics of drug binding to gpcrs are complex and depend on several factors, including charge distribution on the receptor surface, ligand–receptor interactions in the binding channel and the binding site, or solvation. Previously, drugs were developed focusing on target affinity and selectivity. However, it is becoming evident that the drug–target residence time, related to the off-rate, is an important parameter for successful drug development. The residence time influences both the on-rate and overall effectiveness of drugs. Due to recent efforts in the development of fast computers, md simulations and related techniques allow calculation of the binding pathways of ligands and estimation of rate constants 3. Protease-activated receptors (pars) are a ubiquitously expressed class of g-protein-coupled receptors (gpcrs) that enable cells to respond to proteases in the extracellular environment in a nuanced and dynamic manner. Two agents targeting par1, recombinant activated protein c and vorapaxar, are US FDA approved. However, their use has been limited by questions of efficacy and safety, respectively.
 

The method by which a drug is delivered can have a significant effect on its efficacy. To minimize drug degradation and loss, to prevent harmful side-effects and to increase drug bioavailability and the fraction of the drug accumulated in the required zone, various drug delivery and drug targeting systems are currently under development. Attempts are being made to develop therapeutic proteins for cancer, hepatitis, and autoimmune conditions, but their clinical applications are limited, except in the cases of drugs based on erythropoietin, granulocyte colony-stimulating factor, interferon-alpha, and antibodies, owing to problems with fundamental technologies for protein drug discovery. Technologies profiled include those used for biomarker and target discovery such as high throughput screening, signal transduction, micro array, RNAi, metabolomics, toxicogenomics, biosensors and nanotechnology. Colloidal drug carrier systems such as micellar solutions, vesicle and liquid crystal dispersions, as well as nanoparticle dispersions consisting of small particles of 10–400 nm diameter show great promise as drug delivery systems
 

Chemical biology is the study of the chemicals and chemical reactions involved in biological processes, incorporating the disciplines of bioorganic chemistry, biochemistry, cell biology and pharmacology. Chemicals – including natural small molecules, such as lipids, carbohydrates and metals, or non-natural probe or drug molecules – are used to gain insight into biological problems at a mechanistic level. There are some biological problems demand molecular and quantitative answers that can only be supplied by tools and approaches derived from chemistry — such as single-molecule measurements, single-cell imaging, and the use of exogenous molecules to modulate the activity of cellular components. While yeast metabolic engineering has focused on assembling pathways in the cell cytosol, there is growing interest in embracing subcellular compartmentalization. Beyond harnessing distinct organelle properties, physical separation of organelles from the cytosol has the potential to eliminate metabolic crosstalk and enhance compartmentalized pathway efficiency.

In Current Opinion in Chemical Biology, we help the reader by providing in a systematic manner:

1. The views of experts on current advances in chemical biology in a clear and readable form.

2. Evaluations of the most interesting papers, annotated by experts, from the great wealth of original publications.

 It is important to set clear go/no-go criteria for the progression of hit and lead compounds. A high throughput screening (hts) hit, was optimized and evaluated for the enzymatic inhibition of plk-1 kinase. Molecular modeling suggested the importance of adding a hydrophobic aromatic amine side chain in order to improve the potency by a classic kinase h-donor-acceptor binding mode.  A target is a broad term which can be applied to a range of biological entities which may include for example proteins, genes and RNA. A good target needs to be efficacious, safe, meet clinical and commercial needs and, above all, be ‘druggable’.g-protein-coupled receptors (gpcrs), whereas antibodies are good at blocking protein/protein interactions. Once identified, the target then needs to be fully prosecuted. Validation techniques range from in vitro tools through the use of whole animal models, to modulation of a desired target in disease patients.