@article{fdi:010074329, title = {{A}ntitrypanosomatid pharmacomodulation at position 3 of the 8-nitroquinolin-2(1h)-one scaffold using palladium-catalysed cross-coupling reactions}, author = {{P}edron, {J}. and {B}oudot, {C}. and {B}ourgeade-{D}elmas, {S}andra and {S}ournia-{S}aquet, {A}. and {P}aloque, {L}. and {R}astegari, {M}. and {A}bdoulaye, {M}. and {E}l-{K}ashef, {H}. and {B}onduelle, {C}. and {P}ratviel, {G}. and {W}yllie, {S}. and {F}airlamb, {A}. {H}. and {C}ourtioux, {B}. and {V}erhaeghe, {P}. and {V}alentin, {A}.}, editor = {}, language = {{ENG}}, abstract = {{A}n antikinetoplastid pharmacomodulation study at position 3 of the recently described hit molecule 3-bromo-8-nitroquinolin-2(1{H})-one was conducted. {T}wenty-four derivatives were synthesised using the {S}uzuki-{M}iyaura cross-coupling reaction and evaluated in vitro on both {L}eishmania infantum axenic amastigotes and {T}rypanosoma brucei brucei trypomastigotes. {I}ntroduction of a para-carboxyphenyl group at position 3 of the scaffold led to the selective antitrypanosomal hit molecule 3-(4-carboxyphenyl)-8-nitroquinolin-2(1{H})-one (21) with a lower reduction potential (-0.56{V}) than the initial hit (-0.45{V}). {C}ompound 21 displays micromolar antitrypanosomal activity ({IC}50=1.5m) and low cytotoxicity on the human {H}ep{G}2 cell line ({CC}50=120m), having a higher selectivity index ({SI}=80) than the reference drug eflornithine. {C}ontrary to results previously obtained in this series, hit compound 21 is inactive toward {L}.infantum and is not efficiently bioactivated by {T}.brucei brucei type{I} nitroreductase, which suggests the existence of an alternative mechanism of action.}, keywords = {8-nitroquinolin-2(1{H})-ones ; antikinetoplastid pharmacomodulation ; palladium-catalysed cross-coupling ; parasitic nitroreductases ; trypanosomatids}, booktitle = {}, journal = {{C}hemmedchem}, volume = {13}, numero = {20}, pages = {2217--2228}, ISSN = {1860-7179}, year = {2018}, DOI = {10.1002/cmdc.201800456}, URL = {https://www.documentation.ird.fr/hor/fdi:010074329}, }