chapter 1 - Bentham Science

More documents

Recommendations

Info

176 Chemoinformatics: Directions Toward Combating Neglected Diseases Taft et al. 1.10. Giardiasis Giardiasis infects over 2.5 million people annually. In humans, it is caused by the infection of the small intestine by a single-celled organism and occurs worldwide with a prevalence of 20-30% in developing countries. It has a wide range of human and other mammalian hosts making it very difficult to eliminate [46]. 1.11. Amebiasis Amebiasis is an intestinal illness that is typically transmitted when someone eats or drinks something contaminated with a microscopic parasite. In many cases, the parasite lives in a person's large intestine without causing any symptoms. But sometimes, it invades the lining of the large intestine, causing bloody diarrhea, stomachaches, cramping, nausea, loss of appetite, or fever. In rare cases, it can spread into other organs such as the liver, lungs, and brain [47]. 2. CAUSATIVE AGENTS 2.1. Trypanosoma cruzi The hemoflagellate protozoan T. cruzi is the causative agent of the Chagas`s disease, which is transmitted to humans either by blood-sucking reduviid bugs or directly by the transfusion of infected blood. After 10- 20 years, a chronic form of the disease often develops causing irreversible damage to colon, heart and esophagus, which can lead to death. In rural areas, the disease is transmitted by bugs such as Rhodnius prolixus and Triatoma infestans. T. cruzi multiplies within the insect gut as an epimastigote form and is spread as a non-dividing metacycle trypomastigote from the insect excrements by contamination of intact mucosa or wounds produced by the blood-sucking activity of the vector. In the mammalian host, it proliferates intracellularly in the amastigote form and releases into the blood stream as a non-dividing infective trypomastigote [11, 47]. 2.2. Trypanosoma brucei These parasites are the cause of human African trypanosomiasis, i.e., sleeping sickness, which is fatal if untreated. The causative agents are phenotypically and morphologically similar. T. brucei is characterized by the presence of a DNA-containing organelle in the mitochondrion. It also contains a cell membrane (complex grid of microfilaments and microtubules). The outer surface is covered with a single glycoprotein. The parasite has the capability to synthesize aminoacids, and polyamines, compounds essential for proliferation and differentiation of the bloodstream stages. The main thiol is trypanothione, whose metabolism plays an important role in trypanosomal survival. T. brucei is transmitted by species of tsetse flies. The insect vector takes a blood meal from mammals injecting metacyclic trypomastigotes, which transform into bloodstream trypomastigotes, transported to other sites and profilerating by binary fission to different body fluids such as blood, lymph and spinal fluid. The procyclic cell acts as a prototype for the basic architecture of T. brucei. Regulatory pathways controlling the eukaryotic cell cycle involve regulatory proteins such as cyclin dependent kinases and inhibitors possessing distinct roles in the different life cycle stages [4, 11, 47]. 2.3. Protozoan leishmania Leishmaniasis is caused by 20 species of Leishmania (order of Kinetoplastida, family Trypanosomatidae) and transmitted by 30 species of sand fly. Leishmania species are divided into species by geographic location of endemic species. The parasite is carried by the female phlebotamine sandfly of the genus phlebotamus or Lutzomyia. Only two Leishmania species can maintain anthroponotic human-human cycle, i.e., L. donovani, and L. tropica. In the mammalian host, the parasite proliferates as amastigotes intracelluarly within a phagolysosome compartment of macrophages. The extracellular flagellated promastigotes proliferates in the gut of their sand fly vectors, where they multiply and differentiate before emerging as an infectious species. The
Chemoinformatics: Directions Toward Combating Neglected Diseases, 2012, 197-199 197 INDEX A Acethylcolinesterase 58 African trypanosomiasis 4 American trypanosomiasis 7 Amebiasis 9 antitubercular drugs 74 B Balantidiasis 8 C Carbohydrate Biosynthesis 184 Cell Cycle 184 Chagas´ disease 146 Conjugate gradient 134 Cryptosporidiosis 192 Cyclin-Dependent Protein Kinases 183 D Docking study 162 E Erythocyte G protein 183 Electron Transfer Chain and Alternative Oxidase 184 ExPASy Molecular Biology Server 57 F Farnesyl Transferase 183 Fatty Acid Biosynthesis 184 G Glycogen Synthase Kinase 184 H Helicases 183 Histone Deacetylases 184 Homology modeling 49 I Isoprenoid Biosynthesis 184 J Japanese Encephalitis mosquito 59 K Kinetoplast DNA Replication Machinery 184 L Lysosomes 184 Leishmania 38 Leishmaniasis 14 Teodorico C. Ramalho, Matheus P. Freitas and Elaine F. F. da Cunha (Eds) All rights reserved - © 2012 <strong>Bentham</strong> <strong>Science</strong> Publishers
Page 2 and 3: Chemoinformatics: Directions Toward
Page 4 and 5: CONTENTS Foreword i Preface ii List
Page 6 and 7: ii PREFACE Low-income populations i
Page 10 and 11: New Approaches to the Development C
Page 12 and 13: 34 Chemoinformatics: Directions Tow
Page 16 and 17: Antimalarial Agents Chemoinformatic
Page 18 and 19: 70 Chemoinformatics: Directions Tow
Page 22 and 23: Antileishmaniasis Agents Chemoinfor
Page 24 and 25: 146 Chemoinformatics: Directions To
Page 30 and 31: Molecular Modeling of the Toxoplasm

chapter 1 - Bentham Science

Create successful ePaper yourself

Delete template?

Save as template?