Parasitic Disease
Chapters
Antiparasitic Chemotherapy: Tinkering with the Purine Salvage Pathway
Alok Kumar Datta, Rupak Datta and Banibrata Sen
Distinguishable differences between infecting organisms and their respective hosts with respect to metabolism and macromolecular structure provide scopes for detailed characterization of target proteins and/or macromolecules as the focus for the development of selective inhibitors. In order to devel...
Arsenite Resistance in Leishmania and Possible Drug Targets
Gaganmeet Singh, K.G. Jayanarayan and Chinmoy Sankar Dey
Parasitic infections are of enormous public health importance. Leishmaniasis is currently regarded as the second-most dreaded parasitic disease after malaria (WHO). Visceral leishmaniasis or kala-azar, caused by Leishmania donovani, is the most fatal form of leishmaniasis afflicting millions of peop...
DNA Topoisomerases of Leishmania: The Potential Targets for Anti-Leishmanial Therapy
Benu Brata Das, Agneyo Ganguly and Hemanta K. Majumder
Protozoan parasites of the genus Leishmania cause severe diseases that threaten human beings, both for the high mortality rates involved and the economic loss resulting from morbidity, primarily in the tropical and subtropical areas. This ancient eukaryote shows variable genetic diversity in their l...
Drugs and Transporters in Kinetoplastid Protozoa
Scott M. Landfear
Kinetoplastid protozoa express hundreds of membrane transport proteins that allow them to take up nutrients, establish ion gradients, efflux metabolites, translocate compounds from one intracellular compartment to another, and take up or export drugs. The combination of molecular cloning, genetic ap...
Fishing for Anti-Leishmania Drugs: Principles and Problems
Emanuela Handman, Lukasz Kedzierski, Alessandro D. Uboldi and James W. Goding
To date, there are no vaccines against any of the major parasitic diseases including leishmaniasis, and chemotherapy is the main weapon in our arsenal. Current drugs are toxic and expensive, and are losing their effectiveness due to parasite resistance. The availability of the genome sequence of two...
Histone Deacetylases
David Horn
Deacetylation of histones is required for gene regulation and cell cycle progression and the mediators, the histone deacetylases, are being vigorously pursued as drug targets for cancer chemotherapy. The deacetylases are also potential drug targets against infectious diseases and genome sequencing r...
Purine and Pyrimidine Metabolism in Leishmania
Nicola S. Carter, Phillip Yates, Cassandra S. Arendt, Jan M. Boitz and Buddy Ullman
Purines and pyrimidines are indispensable to all life, performing many vital functions for cells: ATP serves as the universal currency of cellular energy, cAMP and cGMP are key second messenger molecules, purine and pyrimidine nucleotides are precursors for activated forms of both carbohydrates and ...
Searching the Tritryp Genomes for Drug Targets
Peter J. Myler
The recent publication of the complete genome sequences of Leishmania major, Trypanosoma brucei and Trypanosoma cruzi revealed that each genome contains 8300-12,000 protein-coding genes, of which ~6500 are common to all three genomes, and ushers in a new, post-genomic, era for trypanosomatid drug di...
Selective Lead Compounds Against Kinetoplastid Tubulin
R.E. Morgan and K.A. Werbovetz
Kinetoplastid parasites are responsible for the potentially fatal diseases leishmaniasis, African sleeping sickness and Chagas disease. The current treatments for these diseases are far from ideal and new compounds are needed as antiparasitic drug candidates. Tubulin is the accepted target for treat...
Sterol 14-Demethylase Inhibitors for Trypanosoma cruzi Infections
Frederick S. Buckner
Chagas disease is caused by infection with the protozoan pathogen, Trypanosoma cruzi. The only approved therapeutics for treating Chagas disease are two nitroheterocyclic compounds (benznidazole and nifurtimox) that are suboptimal due to poor curative activity for chronic Chagas disease and high rat...
Targeting Glycoproteins or Glycolipids and Their Metabolic Pathways for Anti-Parasite Therapy
Sumi Mukhopadhyay nee Bandyopadhyay and Chitra Mandal
Carbohydrate-based therapy, known as glycotherapeutics, is a new and emerging field that promises to be the future hope for combating kinetoplastid infections more efficiently and effectively. Targeting novel glycoproteins/lipids, which are important disease determinants of kinetoplastid diseases, h...
Unique Characteristics of the Kinetoplast DNA Replication Machinery Provide Potential Drug Targets in Trypanosomatids
Dotan Sela, Neta Milman, Irit Kapeller, Aviad Zick, Rachel Bezalel, Nurit Yaffe and Joseph Shlomai
Kinetoplast DNA (kDNA) is a remarkable DNA structure found in the single mitochondrion of flagellated protozoa of the order Kinetoplastida. In various parasitic species of the family Trypanosomatidae, it consists of 5,000-10,000 duplex DNA minicircles (0.5-10 kb) and 25-50 maxicircles (20-40 kb), wh...
