Cysteine proteases as potential targets for anti-trypanosomatid drug discovery
[Display omitted] Leishmaniasis and trypanosomiasis are endemic neglected disease in South America and Africa and considered a significant public health problem, mainly in poor communities. The limitations of the current available therapeutic options, including the lack of specificity, relatively hi...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry 2021-09, Vol.46, p.116365-116365, Article 116365 |
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| creator | Judice, Wagner A.S. Ferraz, Letícia Silva Lopes, Rayssa de Mello Vianna, Luan dos Santos Siqueira, Fábio da Silva Di Iorio, Juliana F. Dalzoto, Laura de Azevedo Maffeis Trujilho, Mariana Nascimento Romero Santos, Taiz dos Reis Machado, Maurício F.M. Rodrigues, Tiago |
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Leishmaniasis and trypanosomiasis are endemic neglected disease in South America and Africa and considered a significant public health problem, mainly in poor communities. The limitations of the current available therapeutic options, including the lack of specificity, relatively high toxicity, and the drug resistance acquiring, drive the constant search for new targets and therapeutic options. Advances in knowledge of parasite biology have revealed essential enzymes involved in the replication, survival, and pathogenicity of Leishmania and Trypanosoma species. In this scenario, cysteine proteases have drawn the attention of researchers and they are being proposed as promising targets for drug discovery of antiprotozoal drugs. In this systematic review, we will provide an update on drug discovery strategies targeting the cysteine proteases as potential targets for chemotherapy against protozoal neglected diseases. |
| doi_str_mv | 10.1016/j.bmc.2021.116365 |
| format | Article |
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Leishmaniasis and trypanosomiasis are endemic neglected disease in South America and Africa and considered a significant public health problem, mainly in poor communities. The limitations of the current available therapeutic options, including the lack of specificity, relatively high toxicity, and the drug resistance acquiring, drive the constant search for new targets and therapeutic options. Advances in knowledge of parasite biology have revealed essential enzymes involved in the replication, survival, and pathogenicity of Leishmania and Trypanosoma species. In this scenario, cysteine proteases have drawn the attention of researchers and they are being proposed as promising targets for drug discovery of antiprotozoal drugs. In this systematic review, we will provide an update on drug discovery strategies targeting the cysteine proteases as potential targets for chemotherapy against protozoal neglected diseases.</description><identifier>ISSN: 0968-0896</identifier><identifier>EISSN: 1464-3391</identifier><identifier>DOI: 10.1016/j.bmc.2021.116365</identifier><identifier>PMID: 34419821</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Chagas disease ; Chemotherapy ; Cysteine proteases ; Cysteine Proteases - metabolism ; Cysteine Proteinase Inhibitors - chemical synthesis ; Cysteine Proteinase Inhibitors - chemistry ; Cysteine Proteinase Inhibitors - pharmacology ; Drug Discovery ; Humans ; Leishmania - drug effects ; Leishmania - enzymology ; Leishmaniasis ; Leishmaniasis - drug therapy ; Molecular Structure ; Neglected diseases ; Parasitic Sensitivity Tests ; Trypanocidal Agents - chemical synthesis ; Trypanocidal Agents - chemistry ; Trypanocidal Agents - pharmacology ; Trypanosoma - drug effects ; Trypanosoma - enzymology ; Trypanosomiasis - drug therapy</subject><ispartof>Bioorganic & medicinal chemistry, 2021-09, Vol.46, p.116365-116365, Article 116365</ispartof><rights>2021 Elsevier Ltd</rights><rights>Copyright © 2021 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c396t-d4866cf764c1764a5c7839ad3d30f9acb19275a34c6d40eed1b65f4f23622a7c3</citedby><cites>FETCH-LOGICAL-c396t-d4866cf764c1764a5c7839ad3d30f9acb19275a34c6d40eed1b65f4f23622a7c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bmc.2021.116365$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34419821$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Judice, Wagner A.S.</creatorcontrib><creatorcontrib>Ferraz, Letícia Silva</creatorcontrib><creatorcontrib>Lopes, Rayssa de Mello</creatorcontrib><creatorcontrib>Vianna, Luan dos Santos</creatorcontrib><creatorcontrib>Siqueira, Fábio da Silva</creatorcontrib><creatorcontrib>Di Iorio, Juliana F.</creatorcontrib><creatorcontrib>Dalzoto, Laura de Azevedo Maffeis</creatorcontrib><creatorcontrib>Trujilho, Mariana Nascimento Romero</creatorcontrib><creatorcontrib>Santos, Taiz dos Reis</creatorcontrib><creatorcontrib>Machado, Maurício F.M.</creatorcontrib><creatorcontrib>Rodrigues, Tiago</creatorcontrib><title>Cysteine proteases as potential targets for anti-trypanosomatid drug discovery</title><title>Bioorganic & medicinal chemistry</title><addtitle>Bioorg Med Chem</addtitle><description>[Display omitted]
Leishmaniasis and trypanosomiasis are endemic neglected disease in South America and Africa and considered a significant public health problem, mainly in poor communities. The limitations of the current available therapeutic options, including the lack of specificity, relatively high toxicity, and the drug resistance acquiring, drive the constant search for new targets and therapeutic options. Advances in knowledge of parasite biology have revealed essential enzymes involved in the replication, survival, and pathogenicity of Leishmania and Trypanosoma species. In this scenario, cysteine proteases have drawn the attention of researchers and they are being proposed as promising targets for drug discovery of antiprotozoal drugs. In this systematic review, we will provide an update on drug discovery strategies targeting the cysteine proteases as potential targets for chemotherapy against protozoal neglected diseases.</description><subject>Chagas disease</subject><subject>Chemotherapy</subject><subject>Cysteine proteases</subject><subject>Cysteine Proteases - metabolism</subject><subject>Cysteine Proteinase Inhibitors - chemical synthesis</subject><subject>Cysteine Proteinase Inhibitors - chemistry</subject><subject>Cysteine Proteinase Inhibitors - pharmacology</subject><subject>Drug Discovery</subject><subject>Humans</subject><subject>Leishmania - drug effects</subject><subject>Leishmania - enzymology</subject><subject>Leishmaniasis</subject><subject>Leishmaniasis - drug therapy</subject><subject>Molecular Structure</subject><subject>Neglected diseases</subject><subject>Parasitic Sensitivity Tests</subject><subject>Trypanocidal Agents - chemical synthesis</subject><subject>Trypanocidal Agents - chemistry</subject><subject>Trypanocidal Agents - pharmacology</subject><subject>Trypanosoma - drug effects</subject><subject>Trypanosoma - enzymology</subject><subject>Trypanosomiasis - drug therapy</subject><issn>0968-0896</issn><issn>1464-3391</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1LAzEQhoMotlZ_gBfZo5et-drsBk9S_IKiFz2HNJktKbubmmSF_ntTWj16mRmGd17eeRC6JnhOMBF3m_mqN3OKKZkTIpioTtCUcMFLxiQ5RVMsRVPiRooJuohxgzGmXJJzNGGcE9lQMkVvi11M4AYotsEn0BFioWOxzfOQnO6KpMMaUixaHwqdV2UKu60efPS9Ts4WNozrwrpo_DeE3SU6a3UX4erYZ-jz6fFj8VIu359fFw_L0jApUml5I4Rpa8ENyUVXpm6Y1JZZhlupzYpIWleacSMsxwCWrETV8pYyQamuDZuh24NvTv01QkyqzxGg6_QAfoyKVhmHFKzhWUoOUhN8jAFatQ2u12GnCFZ7jGqjMka1x6gOGPPNzdF-XPVg_y5-uWXB_UEA-clvB0FF42AwYF0Ak5T17h_7H--Xg30</recordid><startdate>20210915</startdate><enddate>20210915</enddate><creator>Judice, Wagner A.S.</creator><creator>Ferraz, Letícia Silva</creator><creator>Lopes, Rayssa de Mello</creator><creator>Vianna, Luan dos Santos</creator><creator>Siqueira, Fábio da Silva</creator><creator>Di Iorio, Juliana F.</creator><creator>Dalzoto, Laura de Azevedo Maffeis</creator><creator>Trujilho, Mariana Nascimento Romero</creator><creator>Santos, Taiz dos Reis</creator><creator>Machado, Maurício F.M.</creator><creator>Rodrigues, Tiago</creator><general>Elsevier Ltd</general><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>7X8</scope></search><sort><creationdate>20210915</creationdate><title>Cysteine proteases as potential targets for anti-trypanosomatid drug discovery</title><author>Judice, Wagner A.S. ; Ferraz, Letícia Silva ; Lopes, Rayssa de Mello ; Vianna, Luan dos Santos ; Siqueira, Fábio da Silva ; Di Iorio, Juliana F. ; Dalzoto, Laura de Azevedo Maffeis ; Trujilho, Mariana Nascimento Romero ; Santos, Taiz dos Reis ; Machado, Maurício F.M. ; Rodrigues, Tiago</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c396t-d4866cf764c1764a5c7839ad3d30f9acb19275a34c6d40eed1b65f4f23622a7c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Chagas disease</topic><topic>Chemotherapy</topic><topic>Cysteine proteases</topic><topic>Cysteine Proteases - metabolism</topic><topic>Cysteine Proteinase Inhibitors - chemical synthesis</topic><topic>Cysteine Proteinase Inhibitors - chemistry</topic><topic>Cysteine Proteinase Inhibitors - pharmacology</topic><topic>Drug Discovery</topic><topic>Humans</topic><topic>Leishmania - drug effects</topic><topic>Leishmania - enzymology</topic><topic>Leishmaniasis</topic><topic>Leishmaniasis - drug therapy</topic><topic>Molecular Structure</topic><topic>Neglected diseases</topic><topic>Parasitic Sensitivity Tests</topic><topic>Trypanocidal Agents - chemical synthesis</topic><topic>Trypanocidal Agents - chemistry</topic><topic>Trypanocidal Agents - pharmacology</topic><topic>Trypanosoma - drug effects</topic><topic>Trypanosoma - enzymology</topic><topic>Trypanosomiasis - drug therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Judice, Wagner A.S.</creatorcontrib><creatorcontrib>Ferraz, Letícia Silva</creatorcontrib><creatorcontrib>Lopes, Rayssa de Mello</creatorcontrib><creatorcontrib>Vianna, Luan dos Santos</creatorcontrib><creatorcontrib>Siqueira, Fábio da Silva</creatorcontrib><creatorcontrib>Di Iorio, Juliana F.</creatorcontrib><creatorcontrib>Dalzoto, Laura de Azevedo Maffeis</creatorcontrib><creatorcontrib>Trujilho, Mariana Nascimento Romero</creatorcontrib><creatorcontrib>Santos, Taiz dos Reis</creatorcontrib><creatorcontrib>Machado, Maurício F.M.</creatorcontrib><creatorcontrib>Rodrigues, Tiago</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Bioorganic & medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Judice, Wagner A.S.</au><au>Ferraz, Letícia Silva</au><au>Lopes, Rayssa de Mello</au><au>Vianna, Luan dos Santos</au><au>Siqueira, Fábio da Silva</au><au>Di Iorio, Juliana F.</au><au>Dalzoto, Laura de Azevedo Maffeis</au><au>Trujilho, Mariana Nascimento Romero</au><au>Santos, Taiz dos Reis</au><au>Machado, Maurício F.M.</au><au>Rodrigues, Tiago</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cysteine proteases as potential targets for anti-trypanosomatid drug discovery</atitle><jtitle>Bioorganic & medicinal chemistry</jtitle><addtitle>Bioorg Med Chem</addtitle><date>2021-09-15</date><risdate>2021</risdate><volume>46</volume><spage>116365</spage><epage>116365</epage><pages>116365-116365</pages><artnum>116365</artnum><issn>0968-0896</issn><eissn>1464-3391</eissn><abstract>[Display omitted]
Leishmaniasis and trypanosomiasis are endemic neglected disease in South America and Africa and considered a significant public health problem, mainly in poor communities. The limitations of the current available therapeutic options, including the lack of specificity, relatively high toxicity, and the drug resistance acquiring, drive the constant search for new targets and therapeutic options. Advances in knowledge of parasite biology have revealed essential enzymes involved in the replication, survival, and pathogenicity of Leishmania and Trypanosoma species. In this scenario, cysteine proteases have drawn the attention of researchers and they are being proposed as promising targets for drug discovery of antiprotozoal drugs. In this systematic review, we will provide an update on drug discovery strategies targeting the cysteine proteases as potential targets for chemotherapy against protozoal neglected diseases.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>34419821</pmid><doi>10.1016/j.bmc.2021.116365</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Chagas disease Chemotherapy Cysteine proteases Cysteine Proteases - metabolism Cysteine Proteinase Inhibitors - chemical synthesis Cysteine Proteinase Inhibitors - chemistry Cysteine Proteinase Inhibitors - pharmacology Drug Discovery Humans Leishmania - drug effects Leishmania - enzymology Leishmaniasis Leishmaniasis - drug therapy Molecular Structure Neglected diseases Parasitic Sensitivity Tests Trypanocidal Agents - chemical synthesis Trypanocidal Agents - chemistry Trypanocidal Agents - pharmacology Trypanosoma - drug effects Trypanosoma - enzymology Trypanosomiasis - drug therapy |
| title | Cysteine proteases as potential targets for anti-trypanosomatid drug discovery |
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