![](/assets/avatars/avatar-publication-2b3a351ab8b28cb9a7c06c893c869371629a1d64af51e17f2d5acb918f409ac8.png)
High-Throughput Phenotypic Screening and Machine Learning Methods Enabled the Selection of Broad-Spectrum Low-Toxicity Antitrypanosomatidic Agents.
![](/assets/famfamfam_silk/page_white_go-86bc8a425155f07488254af3fe522b8994f78c87c9bb079f9eeac46fa8f9dbd1.png)
![](/assets/famfamfam_silk/script_go-a85fdda7d53d5e9a011c4f835e16e8f02c4859b3fcd6d4cb5e09c9615ee8ce79.png)
Broad-spectrum anti-infective chemotherapy agents with activity against Trypanosomes, Leishmania, and Mycobacterium tuberculosis species were identified from a high-throughput phenotypic screening program of the 456 compounds belonging to the Ty-Box, an in-house industry database. Compound characterization using machine learning approaches enabled the identification and synthesis of 44 compounds with broad-spectrum antiparasitic activity and minimal toxicity against Trypanosoma brucei, Leishmania Infantum, and Trypanosoma cruzi. In vitro studies confirmed the predictive models identified in compound 40 which emerged as a new lead, featured by an innovative N-(5-pyrimidinyl)benzenesulfonamide scaffold and promising low micromolar activity against two parasites and low toxicity. Given the volume and complexity of data generated by the diverse high-throughput screening assays performed on the compounds of the Ty-Box library, the chemoinformatic and machine learning tools enabled the selection of compounds eligible for further evaluation of their biological and toxicological activities and aided in the decision-making process toward the design and optimization of the identified lead.
SEEK ID: https://publications.h-its.org/publications/1734
PubMed ID: 37921561
Research Groups: Scientific Databases and Visualisation
Publication type: Journal
Journal: J Med Chem
Citation: J Med Chem. 2023 Nov 3. doi: 10.1021/acs.jmedchem.3c01322.
Date Published: 3rd Nov 2023
Registered Mode: by PubMed ID
![help](/assets/famfamfam_silk/information-8cfe563be76fb11b27c8ba778f5d40ce6800b244d6ca58ef6e9973308efbe534.png)
Views: 1222
Created: 6th Nov 2023 at 10:06
Last updated: 5th Mar 2024 at 21:25
![help](/assets/famfamfam_silk/information-8cfe563be76fb11b27c8ba778f5d40ce6800b244d6ca58ef6e9973308efbe534.png)
This item has not yet been tagged.
![help](/assets/famfamfam_silk/information-8cfe563be76fb11b27c8ba778f5d40ce6800b244d6ca58ef6e9973308efbe534.png)
None