{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Donlin MJ"],"funding":["National Institute of Neurological Disorders and Stroke","National Institute of Allergy and Infectious Diseases","NIAID NIH HHS","Saint Louis University","NINDS NIH HHS","National Institute of General Medical Sciences","NIGMS NIH HHS"],"pagination":["774-781"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8155264"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["12(5)"],"pubmed_abstract":["Opportunistic infections from pathogenic fungi present a major challenge to healthcare because of a very limited arsenal of antifungal drugs, an increasing population of immunosuppressed patients, and increased prevalence of resistant clinical strains due to overuse of the few available antifungals. Cryptococcal meningitis is a life-threatening opportunistic fungal infection caused by one of two species in the <i>Cryptococcus</i> genus, <i>Cryptococcus neoformans</i> and <i>Cryptococcus gattii</i>. Eighty percent of cryptococcosis diseases are caused by <i>C. neoformans</i> that is endemic in the environment. The standard of care is limited to old antifungals, and under a high standard of care, mortality remains between 10 and 30%. We have identified a series of 5-nitro-6-thiocyanatopyrimidine antifungal drug candidates using <i>in vitro</i> and computational machine learning approaches. These compounds can inhibit <i>C. neoformans</i> growth at submicromolar levels, are effective against fluconazole-resistant <i>C. neoformans</i> and a clinical strain of <i>C. gattii</i>, and are not antagonistic with currently approved antifungals."],"journal":["ACS medicinal chemistry letters"],"pubmed_title":["Discovery of 5-Nitro-6-thiocyanatopyrimidines as Inhibitors of <i>Cryptococcus neoformans</i> and <i>Cryptococcus gattii</i>."],"pmcid":["PMC8155264"],"funding_grant_id":["R01 AI123407","R01 NS102164","R44GM122196-02A1","1R01NS102164-01","R44 GM122196","R01AI123407"],"pubmed_authors":["Riabova O","Ekins S","Makarov V","Lepioshkin A","Xu E","Lin J","Donlin MJ","Lane TR"],"additional_accession":[]},"is_claimable":false,"name":"Discovery of 5-Nitro-6-thiocyanatopyrimidines as Inhibitors of <i>Cryptococcus neoformans</i> and <i>Cryptococcus gattii</i>.","description":"Opportunistic infections from pathogenic fungi present a major challenge to healthcare because of a very limited arsenal of antifungal drugs, an increasing population of immunosuppressed patients, and increased prevalence of resistant clinical strains due to overuse of the few available antifungals. Cryptococcal meningitis is a life-threatening opportunistic fungal infection caused by one of two species in the <i>Cryptococcus</i> genus, <i>Cryptococcus neoformans</i> and <i>Cryptococcus gattii</i>. Eighty percent of cryptococcosis diseases are caused by <i>C. neoformans</i> that is endemic in the environment. The standard of care is limited to old antifungals, and under a high standard of care, mortality remains between 10 and 30%. We have identified a series of 5-nitro-6-thiocyanatopyrimidine antifungal drug candidates using <i>in vitro</i> and computational machine learning approaches. These compounds can inhibit <i>C. neoformans</i> growth at submicromolar levels, are effective against fluconazole-resistant <i>C. neoformans</i> and a clinical strain of <i>C. gattii</i>, and are not antagonistic with currently approved antifungals.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 May","modification":"2025-04-04T20:15:48.371Z","creation":"2025-04-04T20:15:48.371Z"},"accession":"S-EPMC8155264","cross_references":{"pubmed":["34055225"],"doi":["10.1021/acsmedchemlett.1c00038"]}}