{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T03:08:34Z","timestamp":1767236914372,"version":"3.37.3"},"reference-count":0,"publisher":"Bentham Science Publishers Ltd.","issue":"28","funder":[{"DOI":"10.13039\/501100001871","name":"Applied Molecular Biosciences Unit \u2013 UCIBIO financed by national funds from FCT","doi-asserted-by":"publisher","award":["UIBD\/04378\/2020"],"award-info":[{"award-number":["UIBD\/04378\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["eurekaselect.com"],"crossmark-restriction":true},"short-container-title":["CMC"],"published-print":{"date-parts":[[2021,9,9]]},"abstract":"<jats:sec>\n<jats:title\/>\n<jats:p>In spite of the medical and technological developments of the last centuries,\nTuberculosis (TB) has remained a challenging disease, with a limited number of therapeutic\noptions, particularly in light of the increase in drug-resistant cases. The search for new\nmolecules continues, with several candidates currently in clinical testing and ongoing efforts\nto identify novel targets. This work summarizes recent developments on anti-TB\ntherapy, starting by discussing the current epidemiologic status and presenting an\noverview of the history of anti-tuberculosis drug discovery. Special attention is dedicated\nto five multifunctional enzymes that are regarded as promising targets for new anti-TB\ndrugs: 5-aminoimidazole-4-carboxamide ribonucleotide transformylase\/IMP cyclohydrolase\n(ATIC); 3,4-dihydroxy-2-butanone 4-phosphate synthase (DHBPS)\/GTP cyclohydrolase\nII (GCHII); glutamine dependent NAD+ Synthetase (NadE); chorismate synthase (CS);\nand Tryptophan synthase (TS). These enzymes are involved in metabolic pathways\ncritical for the M. tuberculosis survival, growth or replication, but that are not expressed\nin humans or have significant differences in terms of functionality, which makes them appealing\ntargets. Their function, structure, possible catalytic mechanisms, and current inhibition\nstrategies and inhibitors are reviewed and discussed.<\/jats:p>\n<\/jats:sec>","DOI":"10.2174\/0929867328666201229122722","type":"journal-article","created":{"date-parts":[[2020,12,29]],"date-time":"2020-12-29T16:42:15Z","timestamp":1609260135000},"page":"5847-5882","update-policy":"https:\/\/doi.org\/10.2174\/bsp_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Multifunctional Enzymes as Targets for the Treatment of Tuberculosis: Paving the Way for New Anti-TB Drugs"],"prefix":"10.2174","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8422-9392","authenticated-orcid":true,"given":"Carla S\u00edlvia Silva","family":"Teixeira","sequence":"first","affiliation":[{"name":"UCIBIO@REQUIMTE, BioSIM, Departamento de Biomedicina da Faculdade de Medicina da Universidade do Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319, Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0342-7424","authenticated-orcid":true,"given":"Nuno M.F.S.A.","family":"Cerqueira","sequence":"additional","affiliation":[{"name":"UCIBIO@REQUIMTE, BioSIM, Departamento de Biomedicina da Faculdade de Medicina da Universidade do Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319, Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6560-5284","authenticated-orcid":true,"given":"S\u00e9rgio Filipe","family":"Sousa","sequence":"additional","affiliation":[{"name":"UCIBIO@REQUIMTE, BioSIM, Departamento de Biomedicina da Faculdade de Medicina da Universidade do Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319, Porto, Portugal"}]}],"member":"965","container-title":["Current Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/eurekaselect.com\/article\/download\/189588","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.eurekaselect.com\/189588\/article","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eurekaselect.com\/article\/download\/189588","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,12]],"date-time":"2021-09-12T10:00:58Z","timestamp":1631440858000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.eurekaselect.com\/189588\/article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,9]]},"references-count":0,"journal-issue":{"issue":"28","published-print":{"date-parts":[[2021,9,9]]}},"alternative-id":["LiveAll1"],"URL":"https:\/\/doi.org\/10.2174\/0929867328666201229122722","relation":{},"ISSN":["0929-8673"],"issn-type":[{"type":"print","value":"0929-8673"}],"subject":[],"published":{"date-parts":[[2021,9,9]]},"assertion":[{"value":"Peer Reviewed","order":0,"name":"review_status","label":"Review Status","group":{"name":"peer_review_details","label":"Peer Review Details"}},{"value":"Single blind","order":1,"name":"review_process","label":"Review Process","group":{"name":"peer_review_details","label":"Peer Review Details"}},{"value":"Checked with iThenticate","order":0,"name":"screening_status","label":"Screening Status","group":{"name":"plagiarism_screening","label":"Plagiarism Screening"}},{"value":"2020-09-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-11-06","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-11-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}