Drug Targets for Plasmodium Falciparum: Historic to Future Perspectives

ISBN-13: 9789811944833 / Angielski / Twarda / 2024

Mohammed Tarique

Opis

This book discusses the current state of knowledge about potential drug targets against malaria. It reviews the current drug targets and focuses on the progress made on the latest scientific and technological advances in discovering and developing novel antimalarial agents. The initial chapter discusses the existing antimalarial agent, including quinoline derivatives, an antifolate, and artemisinin derivatives. It further explores the potential of Plasmodium kinases as drug targets for the treatment of malaria. Notable, the book examines the major metabolic pathways of the parasite that are explored as novel sites for drug design, including heme detoxification, fatty acid synthesis, nucleic acid synthesis, fatty acid synthesis, and oxidative stress. This volume also presents antineoplastic chemotherapy that targets DNA replication and other cancer agents against the malaria parasites with possible off-target action. Lastly, it discusses Plasmodium proteases, a suitable multistage target for designing novel drugs with new modes of action to combat malaria.​

Spis treści

Chapter 1_Existing antimalarial drugs. - Chapter 2_Novel Antimalarial Targets. - Chapter 2.1_Parasite Proteases. - Chapter 2.2_Protein kinases. - Chapter 2.3_Transporters as potential drug targets. - Chapter 2.3.1_Plasmodium Sugar Transporter. - Chapter 2.3.2_Lactate Transporter. - Chapter 2.3.3_P‑Type Na+ATPase. - Chapter 2.3.4_V‑Type H +–ATPase. - Chapter 2.3.5_Aquaporin-3. - Chapter 2.3.6_Choline Transport. - Chapter 2.3.7_Dihydroorotate Dehydrogenase. - Chapter 2.4_Isoprenoid Biosynthesis. - Chapter 2.4.1_Farnesyltransferase. - Chapter 2.5_DNA Targets. - Chapter 2.6_P. falciparum Translational Elongation Factor 2. - Chapter 2.7_Anti-Adhesive Polysaccharide. - Chapter 2.8_Metabolic enzymes as potential drug targets. - Chapter 2.9_Heast shock proteins as targets for novel antimalarial drugs.

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O autorze

Dr Pawan Malhotra’s group at ICGEB has been involved in understanding malaria parasite biology with an aim to identify new drug and vaccine targets. Recently the group has demonstrated Plasmodium Heme Detoxification Protein (HDP) protein as a target for new drug discovery (J. Med Chem. 2017). Earlier, the laboratory illustrated a hemoglobin degradation and Hemozoin (Hz) formation complex and showed the mode of action of two current anti-malarials; chloroquine and artimisinin. Presently they are working on the discovery new class of antimalarials that act on this pathway. A part of this work has been published in Proc Natl Acad Sci, USA, 2013. Dr Malhotra's group has illustrated “Methylene” of Plasmodium falciparum for the first time at asexual blood stages. The group has performed systematic studies to identify 27 novel secretory proteins with adhesive, immunomodulatory and signaling domains and characterized two of these proteins; PfDegP and PfCCp1 for their roles in combating oxidative/thermal stresses. (Mol. Cell. Prot, 2009; FEBS J, 2013 & Biochem J, 2018).  The group has also been involved in identifying novel receptor-ligand interactions with an aim to develop an efficacious malaria vaccine or drug that can block merozoite invasion of human RBCs. They identified ICAMs and Cyclophilin B as common receptors for the invasion of Mtb and malaria into their respective hosts (Nat Comm. 2015; 2017). In addition, they recently have shown a novel gliding complex in P. falciparum that can be targeted for new antimalarial discovery.

Dr. Mohammed Tarique is a Dr. D.S. Kothari Postdoctoral Fellow at the Center for Interdisciplinary Research in Basic Sciences (CIRBSc), Jamia Millia Islamia, India. Holding a Ph.D. in Plasmodium Biology from the International Centre for Genetic Engineering and Biotechnology, New Delhi, India, his research focuses on understanding the biology of plasmodium towards the development of novel drugs. He has published more than 20 research articles in leading peer-reviewed international journals. Currently serves on the editorial boards of numerous journals, including the International Research Journal of Engineering and Technology, American Journal of BioScience, and Cell & Cellular Life Sciences Journal.