Recent Progress in the Development of New Antimalarial Drugs with Novel Targets
Malaria is a major global health problem that causes significant mortality and morbidity annually. The therapeutic options are scarce and massively challenged by the emergence of resistant parasite strains, which causes a major obstacle to malaria control. To prevent a potential public health emerge...
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| description | Malaria is a major global health problem that causes significant mortality and morbidity annually. The therapeutic options are scarce and massively challenged by the emergence of resistant parasite strains, which causes a major obstacle to malaria control. To prevent a potential public health emergency, there is an urgent need for new antimalarial drugs, with single-dose cures, broad therapeutic potential, and novel mechanism of action. Antimalarial drug development can follow several approaches ranging from modifications of existing agents to the design of novel agents that act against novel targets. Modern advancement in the biology of the parasite and the availability of the different genomic techniques provide a wide range of novel targets in the development of new therapy. Several promising targets for drug intervention have been revealed in recent years. Therefore, this review focuses on the progress made on the latest scientific and technological advances in the discovery and development of novel antimalarial agents. Among the most interesting antimalarial target proteins currently studied are proteases, protein kinases, Plasmodium sugar transporter inhibitor, aquaporin-3 inhibitor, choline transport inhibitor, dihydroorotate dehydrogenase inhibitor, isoprenoid biosynthesis inhibitor, farnesyltransferase inhibitor and enzymes are involved in lipid metabolism and DNA replication. This review summarizes the novel molecular targets and their inhibitors for antimalarial drug development approaches. |
| doi_str_mv | 10.2147/DDDT.S265602 |
| format | Article |
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The therapeutic options are scarce and massively challenged by the emergence of resistant parasite strains, which causes a major obstacle to malaria control. To prevent a potential public health emergency, there is an urgent need for new antimalarial drugs, with single-dose cures, broad therapeutic potential, and novel mechanism of action. Antimalarial drug development can follow several approaches ranging from modifications of existing agents to the design of novel agents that act against novel targets. Modern advancement in the biology of the parasite and the availability of the different genomic techniques provide a wide range of novel targets in the development of new therapy. Several promising targets for drug intervention have been revealed in recent years. Therefore, this review focuses on the progress made on the latest scientific and technological advances in the discovery and development of novel antimalarial agents. Among the most interesting antimalarial target proteins currently studied are proteases, protein kinases, Plasmodium sugar transporter inhibitor, aquaporin-3 inhibitor, choline transport inhibitor, dihydroorotate dehydrogenase inhibitor, isoprenoid biosynthesis inhibitor, farnesyltransferase inhibitor and enzymes are involved in lipid metabolism and DNA replication. This review summarizes the novel molecular targets and their inhibitors for antimalarial drug development approaches.</description><identifier>ISSN: 1177-8881</identifier><identifier>EISSN: 1177-8881</identifier><identifier>DOI: 10.2147/DDDT.S265602</identifier><identifier>PMID: 33061294</identifier><language>eng</language><publisher>ALBANY: Dove Medical Press Ltd</publisher><subject>Animals ; Antimalarial agents ; Antimalarials - chemical synthesis ; Antimalarials - chemistry ; Antimalarials - pharmacology ; Artemisinin ; Asexuality ; Biosynthesis ; Blood ; Care and treatment ; Chemistry, Medicinal ; Choline ; Cures ; Cytochrome ; Design modifications ; Dihydrofolate reductase ; Dihydroorotate dehydrogenase ; DNA biosynthesis ; Drug Development ; Drug dosages ; Drug resistance ; Drugs ; Enzymes ; Erythrocytes ; Farnesyltransferase ; Health aspects ; Hemoglobin ; Humans ; Infections ; Kinases ; Life Sciences & Biomedicine ; Lipid metabolism ; Lipids ; Malaria ; Malaria - drug therapy ; Methylene blue ; mode of action ; Morbidity ; Mortality ; Natural products ; novel targets ; Parasite resistance ; Parasites ; Parasitic Sensitivity Tests ; Pharmacology & Pharmacy ; Physiological aspects ; plasmodium ; Plasmodium falciparum - drug effects ; Proteases ; Protein kinase ; Protein transport ; Proteins ; Public health ; Pyrimethamine ; Review ; Science & Technology ; Vector-borne diseases ; World War II</subject><ispartof>Drug design, development and therapy, 2020-01, Vol.14, p.3875-3889</ispartof><rights>2020 Belete.</rights><rights>COPYRIGHT 2020 Dove Medical Press Limited</rights><rights>2020. This work is licensed under https://creativecommons.org/licenses/by-nc/3.0/ (the “License”). 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The therapeutic options are scarce and massively challenged by the emergence of resistant parasite strains, which causes a major obstacle to malaria control. To prevent a potential public health emergency, there is an urgent need for new antimalarial drugs, with single-dose cures, broad therapeutic potential, and novel mechanism of action. Antimalarial drug development can follow several approaches ranging from modifications of existing agents to the design of novel agents that act against novel targets. Modern advancement in the biology of the parasite and the availability of the different genomic techniques provide a wide range of novel targets in the development of new therapy. Several promising targets for drug intervention have been revealed in recent years. Therefore, this review focuses on the progress made on the latest scientific and technological advances in the discovery and development of novel antimalarial agents. Among the most interesting antimalarial target proteins currently studied are proteases, protein kinases, Plasmodium sugar transporter inhibitor, aquaporin-3 inhibitor, choline transport inhibitor, dihydroorotate dehydrogenase inhibitor, isoprenoid biosynthesis inhibitor, farnesyltransferase inhibitor and enzymes are involved in lipid metabolism and DNA replication. This review summarizes the novel molecular targets and their inhibitors for antimalarial drug development approaches.</description><subject>Animals</subject><subject>Antimalarial agents</subject><subject>Antimalarials - chemical synthesis</subject><subject>Antimalarials - chemistry</subject><subject>Antimalarials - pharmacology</subject><subject>Artemisinin</subject><subject>Asexuality</subject><subject>Biosynthesis</subject><subject>Blood</subject><subject>Care and treatment</subject><subject>Chemistry, Medicinal</subject><subject>Choline</subject><subject>Cures</subject><subject>Cytochrome</subject><subject>Design modifications</subject><subject>Dihydrofolate reductase</subject><subject>Dihydroorotate dehydrogenase</subject><subject>DNA biosynthesis</subject><subject>Drug Development</subject><subject>Drug dosages</subject><subject>Drug resistance</subject><subject>Drugs</subject><subject>Enzymes</subject><subject>Erythrocytes</subject><subject>Farnesyltransferase</subject><subject>Health aspects</subject><subject>Hemoglobin</subject><subject>Humans</subject><subject>Infections</subject><subject>Kinases</subject><subject>Life Sciences & Biomedicine</subject><subject>Lipid metabolism</subject><subject>Lipids</subject><subject>Malaria</subject><subject>Malaria - drug therapy</subject><subject>Methylene blue</subject><subject>mode of action</subject><subject>Morbidity</subject><subject>Mortality</subject><subject>Natural products</subject><subject>novel targets</subject><subject>Parasite resistance</subject><subject>Parasites</subject><subject>Parasitic Sensitivity Tests</subject><subject>Pharmacology & Pharmacy</subject><subject>Physiological aspects</subject><subject>plasmodium</subject><subject>Plasmodium falciparum - drug effects</subject><subject>Proteases</subject><subject>Protein kinase</subject><subject>Protein transport</subject><subject>Proteins</subject><subject>Public health</subject><subject>Pyrimethamine</subject><subject>Review</subject><subject>Science & Technology</subject><subject>Vector-borne diseases</subject><subject>World War II</subject><issn>1177-8881</issn><issn>1177-8881</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>AOWDO</sourceid><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><sourceid>DOA</sourceid><recordid>eNqNkt-LEzEQxxdRvPP0zWdZEETQ1mSz-bEvQmn9cXDcidbnkM1Otjm2m16SveJ_b_ZaSys-mDwkzHzmO5PJZNlLjKYFLvmHxWKxnP4oGGWoeJSdY8z5RAiBHx_dz7JnIdwixAgr0NPsjBDEcFGV59nNd9DQx_ybd62HEHLb53EF-QLuoXOb9ehzJr-GbT7ro12rTnmrunzhhzbkWxtX-bVLaL5UvoUYnmdPjOoCvNifF9nPz5-W86-Tq5svl_PZ1URTzuKk4bwSuqaqVrjBDW9EVTdYlboqlCkYQ3XNhSk1xwhRgjmqBBGFUGAIoJoicpFd7nQbp27lxqfK_C_plJUPBudbqXy0ugMJijXUlDUtOZQaaC14QQzXKqXghKuk9XGntRnqNTRjP7zqTkRPPb1dydbdS05xJdhYzNu9gHd3A4Qo1zZo6DrVgxuCLEqKEyeqMqGv_0Jv3eD71KoHijLOUnUHqlXpAbY3LuXVo6icMSJEyRgf007_QaXdwNpq14OxyX4S8OYoYAWqi6vguiFa14dT8P0O1N6F4MEcmoGRHKdOjlMn91OX8FfHDTzAf8YsAe92wBZqZ4K20Gs4YCj9MSeCpr9OCyda_D89t1GN9c_d0EfyG7it8GM</recordid><startdate>20200101</startdate><enddate>20200101</enddate><creator>Belete, Tafere Mulaw</creator><general>Dove Medical Press Ltd</general><general>Dove Medical Press Limited</general><general>Taylor & Francis Ltd</general><general>Dove</general><general>Dove Medical Press</general><scope>AOWDO</scope><scope>BLEPL</scope><scope>DTL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QO</scope><scope>7RV</scope><scope>7XB</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>KB0</scope><scope>M2O</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-6634-5971</orcidid></search><sort><creationdate>20200101</creationdate><title>Recent Progress in the Development of New Antimalarial Drugs with Novel Targets</title><author>Belete, Tafere Mulaw</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c576t-d7798cb5aba1d1d7d89bd1a4c92af2660bb78f4c710053170983828aef3e0b503</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Antimalarial agents</topic><topic>Antimalarials - chemical synthesis</topic><topic>Antimalarials - chemistry</topic><topic>Antimalarials - pharmacology</topic><topic>Artemisinin</topic><topic>Asexuality</topic><topic>Biosynthesis</topic><topic>Blood</topic><topic>Care and treatment</topic><topic>Chemistry, Medicinal</topic><topic>Choline</topic><topic>Cures</topic><topic>Cytochrome</topic><topic>Design modifications</topic><topic>Dihydrofolate reductase</topic><topic>Dihydroorotate dehydrogenase</topic><topic>DNA biosynthesis</topic><topic>Drug Development</topic><topic>Drug dosages</topic><topic>Drug resistance</topic><topic>Drugs</topic><topic>Enzymes</topic><topic>Erythrocytes</topic><topic>Farnesyltransferase</topic><topic>Health aspects</topic><topic>Hemoglobin</topic><topic>Humans</topic><topic>Infections</topic><topic>Kinases</topic><topic>Life Sciences & Biomedicine</topic><topic>Lipid metabolism</topic><topic>Lipids</topic><topic>Malaria</topic><topic>Malaria - drug therapy</topic><topic>Methylene blue</topic><topic>mode of action</topic><topic>Morbidity</topic><topic>Mortality</topic><topic>Natural products</topic><topic>novel targets</topic><topic>Parasite resistance</topic><topic>Parasites</topic><topic>Parasitic Sensitivity Tests</topic><topic>Pharmacology & Pharmacy</topic><topic>Physiological aspects</topic><topic>plasmodium</topic><topic>Plasmodium falciparum - drug effects</topic><topic>Proteases</topic><topic>Protein kinase</topic><topic>Protein transport</topic><topic>Proteins</topic><topic>Public health</topic><topic>Pyrimethamine</topic><topic>Review</topic><topic>Science & Technology</topic><topic>Vector-borne diseases</topic><topic>World War II</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Belete, Tafere Mulaw</creatorcontrib><collection>Web of Science - Science Citation Index Expanded - 2020</collection><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Drug design, development and therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Belete, Tafere Mulaw</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Recent Progress in the Development of New Antimalarial Drugs with Novel Targets</atitle><jtitle>Drug design, development and therapy</jtitle><stitle>DRUG DES DEV THER</stitle><addtitle>Drug Des Devel Ther</addtitle><date>2020-01-01</date><risdate>2020</risdate><volume>14</volume><spage>3875</spage><epage>3889</epage><pages>3875-3889</pages><issn>1177-8881</issn><eissn>1177-8881</eissn><abstract>Malaria is a major global health problem that causes significant mortality and morbidity annually. The therapeutic options are scarce and massively challenged by the emergence of resistant parasite strains, which causes a major obstacle to malaria control. To prevent a potential public health emergency, there is an urgent need for new antimalarial drugs, with single-dose cures, broad therapeutic potential, and novel mechanism of action. Antimalarial drug development can follow several approaches ranging from modifications of existing agents to the design of novel agents that act against novel targets. Modern advancement in the biology of the parasite and the availability of the different genomic techniques provide a wide range of novel targets in the development of new therapy. Several promising targets for drug intervention have been revealed in recent years. Therefore, this review focuses on the progress made on the latest scientific and technological advances in the discovery and development of novel antimalarial agents. Among the most interesting antimalarial target proteins currently studied are proteases, protein kinases, Plasmodium sugar transporter inhibitor, aquaporin-3 inhibitor, choline transport inhibitor, dihydroorotate dehydrogenase inhibitor, isoprenoid biosynthesis inhibitor, farnesyltransferase inhibitor and enzymes are involved in lipid metabolism and DNA replication. This review summarizes the novel molecular targets and their inhibitors for antimalarial drug development approaches.</abstract><cop>ALBANY</cop><pub>Dove Medical Press Ltd</pub><pmid>33061294</pmid><doi>10.2147/DDDT.S265602</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0002-6634-5971</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antimalarial agents Antimalarials - chemical synthesis Antimalarials - chemistry Antimalarials - pharmacology Artemisinin Asexuality Biosynthesis Blood Care and treatment Chemistry, Medicinal Choline Cures Cytochrome Design modifications Dihydrofolate reductase Dihydroorotate dehydrogenase DNA biosynthesis Drug Development Drug dosages Drug resistance Drugs Enzymes Erythrocytes Farnesyltransferase Health aspects Hemoglobin Humans Infections Kinases Life Sciences & Biomedicine Lipid metabolism Lipids Malaria Malaria - drug therapy Methylene blue mode of action Morbidity Mortality Natural products novel targets Parasite resistance Parasites Parasitic Sensitivity Tests Pharmacology & Pharmacy Physiological aspects plasmodium Plasmodium falciparum - drug effects Proteases Protein kinase Protein transport Proteins Public health Pyrimethamine Review Science & Technology Vector-borne diseases World War II |
| title | Recent Progress in the Development of New Antimalarial Drugs with Novel Targets |
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