Materials for Biomedical Applications Edited by Mohammad A. Jafar Mazumder Amir Al-Ahmed Materials for Biomedical Applications Special topic volume with invited peer reviewed papers only. Edited by Mohammad A. Jafar Mazumder and Amir Al-Ahmed Copyright  2014 Trans Tech Publications Ltd, Switzerland All rights reserved. No part of the contents of this publication may be reproduced or transmitted in any form or by any means without the written permission of the publisher. Trans Tech Publications Ltd Churerstrasse 20 CH-8808 Pfaffikon Switzerland http://www.ttp.net Volume 995 of Advanced Materials Research ISSN print 1022-6680 ISSN cd 1022-6680 ISSN web 1662-8985 Full text available online at http://www.scientific.net Distributed worldwide by and in the Americas by Trans Tech Publications Ltd Trans Tech Publications Inc. Churerstrasse 20 PO Box 699, May Street CH-8808 Pfaffikon Enfield, NH 03748 Switzerland USA Phone: +1 (603) 632-7377 Fax: +41 (44) 922 10 33 Fax: +1 (603) 632-5611 e-mail: [email protected] e-mail: [email protected] Preface Biomedical applications of materials as a form of micro to macro molecules provides an outstanding demonstration of the multi- and interdisciplinary arena of materials. The aim of this book is to provide a critical insight on scientific, engineering and processing aspects of various materials, which can ultimately contribute towards the advancement of medical sciences. As the target audiences cover a wide interdisciplinary field, each peer-reviewed chapters written with detail background by a selected group of academic and clinical experts. This book entitled “Materials for Biomedical Applications” reflect the true inter-disciplinary nature of materials science, demonstrate the scientific background and interaction between the materials and biosystems, biocompatible or biodegradable polymers, materials for diagnostic, and the development of devices and enabling technologies for therapeutic applications. This book summarises the up-to-date status of the field, covers important scientific and technological developments by many distinguished experts, who came together to contribute their research work and comprehensive, in-depth and up to date articles. Written in a versatile and contemporary style, this book can be used as an invaluable reference source for graduate students, scientist, researcher working in chemistry, polymer chemistry, polymer engineering, chemical engineering and materials science. We are thankfully appreciate the tremendous efforts and co-operation of all contributing authors for their devotion, valuable time in preparing state- of-art chapters for this book. We would also like to express our gratitude to the publishers and all authors, and others for granting us the copyright permissions to use their illustrations. Although sincere efforts were made to obtain the copyright permissions from the respective owners to include the citation with the reproduced materials, we would like to offer our sincere apologies to any copyright holder if unknowingly their right is being infringed. For acknowledgment, among the editors, Dr. Mohammad A. Jafar Mazumder would like to take this opportunity to express his sincere thanks to Dr. Abdullah J. Al-Hamdan (Chairman, Department of Chemistry, KFUPM) and also to his colleagues at the King Fahd University of Petroleum & Minerals, Saudi Arabia for their endless support and co-operation. Dr. Amir Al-Ahmed, would like to take this opportunity to express his sincere thanks to Dr. Haitham M. Ba-Haidarah (Director CORE-RE, KFUPM) and also to his colleagues at the King Fahd University of Petroleum & Minerals, Saudi Arabia for their never-ending support and co- operation. Without their continuous encouragement, this book would have not been brought into its final form. We would also like to acknowledge the sincere efforts of Mr. Thomas Wohlbier of TTP publishing Authority, in evolving this book into its final shape. Editors Mohammad A. Jafar Mazumder Department of Chemistry King Fahd University of Petroleum & Minerals, Saudi Arabia. Amir Al-Ahmed Center of Research Excellence in Renewable Energy (CORE-RE) King Fahd University of Petroleum & Minerals, Saudi Arabia. Table of Contents Preface Pentose Phosphate Pathway in Disease and Therapy M. Rahman and M.R. Hasan 1 Advanced Materials for Gene Delivery M.A.J. Mazumder, M.H. Zahir and S.F. Zaman 29 Weeds as Alternative Useful Medicinal Source: Mimosa pudica Linn. on Diabetes Mellitus and its Complications T.S. Tunna, Q.U. Ahmed, A.B.M.H. Uddin and M.Z.I. Sarker 49 Substituted Quinoline Derivatives as Potent Biological Agents B. Garudachari and A.M. Isloor 61 Congenital Heart Diseases and Biotechnology: Connecting by Connexin N. Sultana, N. Nakamura, S. Hirose, K. Kutsuzawa, T. Akaike and K. Nag 85 NanoTiO -Enriched Biocompatible Polymeric Powder Coatings: Adhesion, Thermal and 2 Biological Characterizations M.S. Mozumder, A.I. Mourad, H. Perinpanayagam and J. Zhu 113 Nanomaterials in Electrochemical Biosensor M.A. Aziz and M. Oyama 125 Advanced Materials Research Vol. 995 (2014) pp 1-27 © (2014) Trans Tech Publications, Switzerland doi:10.4028/www.scientific.net/AMR.995.1 Pentose Phosphate Pathway in Disease and Therapy Mahbuba Rahman*1 and Mohammad Rubayet Hasan2 1Department of Medicine and 2Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada *Address for correspondence: Room 2K9, 4500 Oak St., Vancouver, BC V6H 2N9, Canada, Email: [email protected] (corresponding author), [email protected] Keywords: Pentose phosphate pathway, glucose-6-phosphate dehydrogenase, transketolase, NADPH, nucleotide biosynthesis, glutathione, metabolic diseases, non-metabolic diseases, cancer, epilepsy, Alzheimer’s disease, chemotherapy, gene therapy, chemoresistance, metabolomics, metabolic flux analysis, novel drug discovery and development. Abstract. Pentose phosphate (PP) pathway, which is ubiquitously present in all living organisms, is one of the major metabolic pathways associated with glucose metabolism. The most important functions of this pathway includes the generation of reducing equivalents in the form of NADPH for reductive biosynthesis, and production of ribose sugars for the biosynthesis of nucleotides, amino acids, and other macromolecules required by all living cells. Under normal conditions of growth, PP pathway is important for cell cycle progression, myelin formation, and the maintenance of the structure and function of brain, liver, cortex and other organs. Under diseased conditions, such as in cases of many metabolic, neurological or malignant diseases, pathological mechanisms augment due to defects in the PP pathway genes. Adoption of alternative metabolic pathways by cells that are metabolically abnormal, or malignant cells that are resistant to chemotherapeutic drugs often plays important roles in disease progression and severity. Accordingly, the PP pathway has been suggested to play critical roles in protecting cancer or abnormal cells by providing reduced environment, to protect cells from oxidative damage and generating structural components for nucleic acids biosynthesis. Novel drugs that targets one or more components of the PP pathway could potentially serve to overcome challenges associated with currently available therapeutic options for many metabolic and non-metabolic diseases. However, careful designing of drugs is critical that takes into the accounts of cell’s broader genomic, proteomic and metabolic contexts under consideration, in order to avoid undesirable side-effects. In this review, we discuss the role of PP pathway under normal and abnormal physiological conditions and the potential of the PP pathway as a target for new drug development to treat metabolic and non-metabolic diseases. Introduction Every living organism, whether it is an unicellular prokaryote or a multicellular eukaryote, possess metabolic pathways to break-down large organic molecules into small intermediary compounds, to generate energy for cellular synthesis [1]. While thousands of enzymes, substrates and co-factors are involved in these reactions, anomalies of the metabolic pathway often affect the life-style of the most complex and multicellular organism on earth, i.e., human. Human being combats much different type of diseases throughout their lifetime. Human disease is defined by impairment of normal functioning because of disordered or abnormal conditions of an organ or the whole body, which may results from the effects of genetic or developmental errors, infection, nutritional deficiency, toxicity, or other unfavourable environmental factors [2]. The cause and effect of disease are multifaceted. Many diseases are caused by pathogenic microorganisms (e.g., virus-influenza, fever, bacteria-tuberculosis, 2 Materials for Biomedical Applications diarrhoea; parasites-malaria, dengue), while others are due to mutation in the genetic element (e.g., autoimmune disease-Systemic lupus erythematosus) or both (e.g., cancer). The effect of the disease can be either acute or chronic. However, the severity of the disease can be life threatening, if it remains undetected or untreated. During the early 20th century, invention of the antimicrobial drug Penicillin, saved lives of thousands of soldiers and civilians from syphilis, staphylococcal and streptococcal infections [3]. New drugs, vaccines, diagnostics and surveillance systems against epidemic diseases like malaria, cholera, pneumococcal infection, tuberculosis, sexually transmitted diseases (STDs) and severe acute respiratory syndrome (SARS) saved thousands of lives worldwide. Insulin and chemotherapy drugs save or increase the longevity of thousands of lives that are suffering from non-infectious diseases such as diabetes or cancer. Malaria and cholera caused by parasites and bacteria, respectively, used to appear in epidemic forms in many developing countries of South-East Asia [4–8]. On the other hand, diabetes, cancer, Alzheimer’s disease, etc., that are associated with genetic factors or other stimuli are now global problem as these have turned into an epidemic form in many developed countries [9-11]. Whatever the cause of the disease is, treatment of diseases certainly impose socio- economic burden for the affected countries. Unfortunately, in recent years, an additional cost has been added to the existing costs associated with the management of human diseases is drug resistance. Not only pathogenic bacteria, but even cancer cells are showing drug resistance properties, causing relapses at later stages of treatment. As a result, it has become highly important to develop new drugs or modify existing treatment strategies. Design and development of novel drugs require knowledge on the metabolic pathways of the infected cells as well as disease causing organisms, whenever applicable [12]. Researchers already identified that many pathogens or even cancer cells adopt alternative pathways for nucleotide synthesis and cell metabolism under diseased conditions. Traditional therapies or new targeted therapies mend abnormal functions of single genes and proteins, as well as affect a narrow range of metabolic downstream reactions. However, metabolic networks inherently possess wide functional flexibility due to the presence of multiple alternate macromolecule synthetic pathways. As a result, targeted drugs may fail to control a pathologic phenotype that eventually develops drug resistance. To overcome these problems, detailed information on the metabolic pathways could pave a solution to the problem of ‘drug resistance’ for the drug developing companies. Use of next generation sequencing technology and proteomics has advanced our understanding of the metabolomics under pathological conditions. Although these data are highly informative, additional information on the cell’s energy state or co-factors might provide useful information under pathological conditions. In this context, metabolic flux analysis (MFA) is a robust technique to understand the biological reactions. MFA applies tracers (e.g., 13C labelled glucose or acetate or 14N labelled glutamine) to detect and calculate the metabolic state of cells [12-14]. In the field of metabolic engineering, this has been applied vastly for strain improvement of biotechnologically important prokaryotic or simple eukaryotic organisms to understand the effect of genetic alterations, changes of external conditions and different nutritional status. Since, mammalian cells exert heterogeneous nature under diseased condition, several tracers are applied to obtain information on diverse metabolites and these data are integrated to the transcriptomic and proteomic data to unravel the correct pathway under pathological condition. Perhaps a similar approach can be applied to narrow down metabolic pathways associated with drug resistance, as well. This review is focussed to discuss the attributes of one of the most important metabolic pathways known as the pentose phosphate (PP) pathway, and human diseases and therapy associated with this pathway. This is the only pathway for nucleotide biosynthesis in both prokaryotes and eukaryotes. There are now ample evidences from in vitro studies that suggest that cancer cells or drug resistant organisms utilize PP pathway for abnormal proliferation or biomass accumulation [15-17]. Defects in the enzymes or genes of this pathway have already been known to be associated with inborn error, heritable or non-heritable diseases, and even with colon cancer, breast cancer etc. Therefore, PP pathway could be a target for new drug development or for modification of existing drug therapies. Therapeutic approaches to correct the mutation of a particular gene or several genes using gene Advanced Materials Research Vol. 995 3 therapy or introduction of small molecule inhibitors or combinations could be promising agents to treat the drug resistance properties of cancer cells. Overview of the Pentose Phosphate Pathway Pentose phosphate pathway is present in every living organism. The history of the metabolic role of this pathway dates back to 1926. Patients treated with the malarial drug primaquine led to the first medical description of a drug- induced hemolytic anemia that correlated with an intrinsic defect of red blood cell metabolism. In 1948, glucose-6P-dehydrogenase, the first rate limiting enzyme of the PP pathway was discovered. In 1960, this pathway was conceived as part of glucose metabolism, based on studies on enzymatic activities and metabolites in yeast [18]. Now it is well established that once glucose enters the cell, it can be used in three major pathways: glycogen synthesis, glycolysis and the PP pathway. While glycogen is used for glucose storage, glycolysis is considered as the key metabolic pathway for glucose metabolism and requires oxygen to generate energy in the form of ATP, NADH and pyruvate. On the other hand, only a very small fraction of glucose (5-30%) is metabolised through the PP pathway. The interplay between the glycolytic pathway and the pentose phosphate pathway are highly dependent on the metabolic state and growth rate of the organism. In human being, PP pathway is most active in liver, mammary glands and adrenal cortex of the brain [19]. Branches of the PP Pathway Cytoplasm or cytosol is the site where pentose phosphates are synthesized from hexose sugars through a series of biochemical reactions. Biochemically, the pentose phosphate pathway is divided into two branches: oxidative branch and the non-oxidative branch. The oxidative branch is operated by three enzymes: glucose 6-phosphate dehydrogenase (G6PDH), 6-phospho gluconolactonase (6PGL) and 6- phosphogluconate dehydrogenase (6PGDH). The substrate of the oxidative branch, glucose-6-phosphate (G6P), is generated from the glycolytic pathway and is oxidized into 6- phosphogluconolactone by G6PDH with the production of NADPH. The unstable lactone ring is then opened by lactonase into 6-phosphogluconic acid and undergoes oxidative decarboxylation by the 6PGDH enzyme, which irreversibly produces ribulose-5-phosphate and a second NADPH and CO . The resulting ribulose-5-phosphate can be further converted into ribose-5-phosphate and used 2 for the synthesis of nucleotides or can be converted into xylulose-5-phosphate and fed into the non- oxidative branch of the pentose phosphphate pathway [20] (Fig. 1). The non-oxidative branch of the pentose phosphate pathway is operated by 4 different enzymes synthesizing 3-7 carbon containing molecules. Unlike the oxidative branch, enzymes of the non- oxidative branch take part in reversible reactions and this occurs mainly during the inter-conversion of ribulose-5-phosphate into ribose-5-phosphate or ribulose-5-phosphate into xylulose-5-phsophate. Enzymes of the non-oxidative branch are ribose-5-phosphate isomerase (R5PI), ribose-5-phosphate epimerase (R5PE), transketolase (TK) and transaldolase (TA). R5PI and R5PE convert ribulose-5- phosphate, synthesized at the oxidative branch, into ribose-5-phosphate and xylulose-5-phosphate, respectively. Ribose-5-phosphate and xylulose-5-phosphate are then catalyzed by TKs into glyceraldehyde-3-phosphate (3- carbon) and sedoheptulose-7-phosphate (7-carbon). These two intermediates are further catalyzed by TAs into fructose-6-phosphate and erythrose-4-phosphate. Erythrose-4-phosphate then reacts with a second xylulose-5-phosphate mediated by the TKs, into the final products fructose-6-phosphate and glyceraldehyde-3-phosphate. These final products are either recycled into the glycolytic pathway for energy production or reintroduced into the PP pathway for biosynthetic reactions [20] (Fig. 1).