{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Singh B"],"funding":["National Institute of Allergy and Infectious Diseases","NIAID NIH HHS"],"pagination":["1972-1989"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9923759"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["66(3)"],"pubmed_abstract":["The carbazole CBL0137 (<b>1</b>) is a lead for drug development against human African trypanosomiasis (HAT), a disease caused by <i>Trypanosoma brucei</i>. To advance <b>1</b> as a candidate drug, we synthesized new analogs that were evaluated for the physicochemical properties, antitrypanosome potency, selectivity against human cells, metabolism in microsomes or hepatocytes, and efflux ratios. Structure-activity/property analyses of analogs revealed eight new compounds with higher or equivalent selectivity indices (<b>5j</b>, <b>5t</b>, <b>5v</b>, <b>5w</b>, <b>5y</b>, <b>8d</b>, <b>13i</b>, and <b>22e</b>). Based on the overall compound profiles, compounds <b>5v</b> and <b>5w</b> were selected for assessment in a mouse model of HAT; while <b>5v</b> demonstrated a lead-like profile for HA"],"journal":["Journal of medicinal chemistry"],"pubmed_title":["Chemical Optimization of CBL0137 for Human African Trypanosomiasis Lead Drug Discovery."],"pmcid":["PMC9923759"],"funding_grant_id":["R01AI126311","R01AI124046","R01 AI124046","R01 AI126311"],"pubmed_authors":["Purmal A","Gadekar PK","Mensa-Wilmot K","Pollastri MP","Singh B","Sanz-Rodriguez CE","Hoffman B","LeBlanc C","Sharma A","Gunaganti N","Greene B","Fu C","Kumar G","Sharif N","Burchfield E","Rivers M","Chichioco M"],"additional_accession":[]},"is_claimable":false,"name":"Chemical Optimization of CBL0137 for Human African Trypanosomiasis Lead Drug Discovery.","description":"The carbazole CBL0137 (<b>1</b>) is a lead for drug development against human African trypanosomiasis (HAT), a disease caused by <i>Trypanosoma brucei</i>. To advance <b>1</b> as a candidate drug, we synthesized new analogs that were evaluated for the physicochemical properties, antitrypanosome potency, selectivity against human cells, metabolism in microsomes or hepatocytes, and efflux ratios. Structure-activity/property analyses of analogs revealed eight new compounds with higher or equivalent selectivity indices (<b>5j</b>, <b>5t</b>, <b>5v</b>, <b>5w</b>, <b>5y</b>, <b>8d</b>, <b>13i</b>, and <b>22e</b>). Based on the overall compound profiles, compounds <b>5v</b> and <b>5w</b> were selected for assessment in a mouse model of HAT; while <b>5v</b> demonstrated a lead-like profile for HA","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Feb","modification":"2026-07-14T20:11:08.806Z","creation":"2025-04-06T02:55:35.385Z"},"accession":"S-EPMC9923759","cross_references":{"pubmed":["36695630"],"doi":["10.1021/acs.jmedchem.2c01767"]}}