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Synthesis and biological evaluation of isoxazolyl-sulfonamides: A non-cytotoxic scaffold active against Trypanosoma cruzi, Leishmania amazonensis and Herpes Simplex Virus.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2018 Nov 01; Vol. 28 (20), pp. 3381-3384. Date of Electronic Publication: 2018 Aug 31. - Publication Year :
- 2018
-
Abstract
- In this study we report the synthesis, characterization, biological evaluation, and druglikeness assessment of a series of 20 novel isoxazolyl-sulfonamides, obtained by a four-step synthetic route. The compounds had their activity against Trypanosoma cruzi, Leishmania amazonensis, Herpes Simplex Virus type 1 and cytotoxicity evaluated in phenotypic assays. All compounds have drug-like properties, showed low cytotoxicity and were promising regarding all other biological activities reported herein, especially the inhibitory activity against T. cruzi. The compounds 8 and 16 showed significant potency and selectivity against T. cruzi (GI <subscript>50</subscript> = 14.3 µM, SI > 34.8 and GI <subscript>50</subscript> = 11.6 µM, SI = 29.1, respectively). These values, close to the values of the reference drug benznidazole (GI <subscript>50</subscript> = 10.2 µM), suggest that compounds 8 and 16 represent promising candidates for further pre-clinical development targeting Chagas disease.<br /> (Copyright © 2018 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Antiviral Agents chemical synthesis
Antiviral Agents chemistry
Antiviral Agents toxicity
Cell Line, Tumor
Cell Survival drug effects
Chlorocebus aethiops
Humans
Isoxazoles chemical synthesis
Isoxazoles chemistry
Isoxazoles toxicity
Leishmania drug effects
Molecular Structure
Simplexvirus drug effects
Structure-Activity Relationship
Sulfonamides chemical synthesis
Sulfonamides chemistry
Sulfonamides toxicity
Trypanocidal Agents chemical synthesis
Trypanocidal Agents chemistry
Trypanocidal Agents toxicity
Trypanosoma cruzi drug effects
Vero Cells
Antiviral Agents pharmacology
Isoxazoles pharmacology
Sulfonamides pharmacology
Trypanocidal Agents pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 28
- Issue :
- 20
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 30194008
- Full Text :
- https://doi.org/10.1016/j.bmcl.2018.08.040