Tawaraishi, T, Ochida, A, Akao, Y, Itono, S, Kamaura, M, Akther, T, Shimada, M, Canan, S, Chowdhury, S, Cao, Y, Condroski, K, Engkvist, O, Francisco, A, Ghosh, S, Kaki, R, Kelly, JM, Kimura, C, Kogej, T, Nagaoka, K, Naito, A, Pairaudeau, G, Radu, C, Roberts, I, Shum, D, Watanabe, N, Xie, H, Yonezawa, S, Yoshida, O, Yoshida, R, Mowbray, C and Perry, B. 2023. Collaborative Virtual Screening Identifies a 2‑Aryl-4-aminoquinazoline Series with Efficacy in an In Vivo Model of Trypanosoma cruzi Infection. [Online]. ACS Publications. Available from: https://doi.org/10.1021/acs.jmedchem.2c00775.s002
Tawaraishi, T, Ochida, A, Akao, Y, Itono, S, Kamaura, M, Akther, T, Shimada, M, Canan, S, Chowdhury, S, Cao, Y, Condroski, K, Engkvist, O, Francisco, A, Ghosh, S, Kaki, R, Kelly, JM, Kimura, C, Kogej, T, Nagaoka, K, Naito, A, Pairaudeau, G, Radu, C, Roberts, I, Shum, D, Watanabe, N, Xie, H, Yonezawa, S, Yoshida, O, Yoshida, R, Mowbray, C and Perry, B. Collaborative Virtual Screening Identifies a 2‑Aryl-4-aminoquinazoline Series with Efficacy in an In Vivo Model of Trypanosoma cruzi Infection [Internet]. ACS Publications; 2023. Available from: https://doi.org/10.1021/acs.jmedchem.2c00775.s002
Tawaraishi, T, Ochida, A, Akao, Y, Itono, S, Kamaura, M, Akther, T, Shimada, M, Canan, S, Chowdhury, S, Cao, Y, Condroski, K, Engkvist, O, Francisco, A, Ghosh, S, Kaki, R, Kelly, JM, Kimura, C, Kogej, T, Nagaoka, K, Naito, A, Pairaudeau, G, Radu, C, Roberts, I, Shum, D, Watanabe, N, Xie, H, Yonezawa, S, Yoshida, O, Yoshida, R, Mowbray, C and Perry, B (2023). Collaborative Virtual Screening Identifies a 2‑Aryl-4-aminoquinazoline Series with Efficacy in an In Vivo Model of Trypanosoma cruzi Infection. [Data Collection]. ACS Publications. https://doi.org/10.1021/acs.jmedchem.2c00775.s002
Description
Probing multiple proprietary pharmaceutical libraries in parallel via virtual screening allowed rapid expansion of the structure–activity relationship (SAR) around hit compounds with moderate efficacy against Trypanosoma cruzi, the causative agent of Chagas Disease. A potency-improving scaffold hop, followed by elaboration of the SAR via design guided by the output of the phenotypic virtual screening efforts, identified two promising hit compounds 54 and 85, which were profiled further in pharmacokinetic studies and in an in vivo model of T. cruzi infection. Compound 85 demonstrated clear reduction of parasitemia in the in vivo setting, confirming the interest in this series of 2-(pyridin-2-yl)quinazolines as potential anti-trypanosome treatments.
Keywords
| Data capture method | Experiment |
|---|---|
| Date (Date published in a 3rd party system) | 6 January 2023 |
| Language(s) of written materials | English |
| Data Creators | Tawaraishi, T, Ochida, A, Akao, Y, Itono, S, Kamaura, M, Akther, T, Shimada, M, Canan, S, Chowdhury, S, Cao, Y, Condroski, K, Engkvist, O, Francisco, A, Ghosh, S, Kaki, R, Kelly, JM, Kimura, C, Kogej, T, Nagaoka, K, Naito, A, Pairaudeau, G, Radu, C, Roberts, I, Shum, D, Watanabe, N, Xie, H, Yonezawa, S, Yoshida, O, Yoshida, R, Mowbray, C and Perry, B |
|---|---|
| LSHTM Faculty/Department | Faculty of Infectious and Tropical Diseases > Department of Infection Biology |
| Participating Institutions | London School of Hygiene & Tropical Medicine, London, United Kingdom |
| Date Deposited | 02 Mar 2023 17:11 |
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| Last Modified | 02 Mar 2023 17:11 |
| Publisher | ACS Publications |
