RT info:eu-repo/semantics/article
T1 Synthesis of Structurally Related Coumarin Derivatives as  Antiproliferative Agents
A1 García González, Celina Elena
A1 Bruna-Haupt, Ezequiel F.
A1 Perretti, Marcelle D.
A1 Garro, Hugo A.
A1 Carrillo,  Romen
A1 Machín,   Félix
A1 Lorenzo-Castrillejo,  Isabel
A1 Gutiérrez,  Lucas
A1 Vega-Hissi,  Esteban G.
A1 Mamberto,  Macarena
A1 Menacho-Marquez,  Mauricio
A1 Fernández,  Claudio O.
A1 García,  Celina
A1 Pungitore,   Carlos R.
A2 Instituto Universitario de Bio-Orgánica Antonio GonzálezULL. Instituto de Investigaciones en Tecnología Química (INTEQUI-CONICET), Universidad Nacional de San Luis, San Luis, Argentina
A2 Química orgánica
K1 Antiproliferative Agents
K1 Genetics
K1 Inhibition,
K1 ,Peptides and proteins
K1 Reaction products
AB A library of structurally related coumarins was generated through synthesis reactions and chemical modification reactions to obtain derivatives with antiproliferative activity both in vivo and in vitro.  Out of a total of 35 structurally related coumarin derivatives, seven of  them showed inhibitory activity in in vitro tests against Taq DNA  polymerase with IC50 values lower than 250 μM. The derivatives 4-  (chloromethyl)-5,7-dihydroxy-2H-chromen-2-one (2d) and 4-  ((acetylthio)methyl)-2-oxo-2H-chromen-7-yl acetate (3c) showed the most promising anti-polymerase activity with IC50 values of 20.7 ± 2.10 and 48.25 ± 1.20 μM, respectively. Assays with tumor cell lines (HEK 293 and HCT-116) were carried out, and the derivative 4-  (chloromethyl)-7,8-dihydroxy-2H-chromen-2-one (2c) was the most promising, with an IC50 value of 8.47 μM and a selectivity index of 1.87. In addition, the derivatives were evaluated against Saccharomyces cerevisiae strains that report about common modes of actions, including DNA damage, that are expected for agents that cause replicative stress. The coumarin derivatives 7-(2-(oxiran-2-yl)ethoxy)-2H-chromen-2-one (5b) and 7-(3-(oxiran-2-yl)propoxy)-2H chromen-2-one (5c) caused DNA damage in S. cerevisiae. The O-alkenylepoxy group stands out as that with the most important functionality within this family of 35 derivatives, presenting a very good profile as an antiproliferative scaffold. Finally, the in vitro antiretroviral capacity was tested through RT-PCR assays. Derivative 5c showed inhibitory activity below 150 μM with an IC50 value of 134.22 ± 2.37 μM, highlighting the O-butylepoxy group as the functionalization responsible for the activity.
YR 2023
FD 2023
LK http://riull.ull.es/xmlui/handle/915/36256
UL http://riull.ull.es/xmlui/handle/915/36256
LA Inglés
NO https://doi.org/10.1021/acsomega.3c03181
DS Repositorio institucional de la Universidad de La Laguna
RD 14-may-2024