Biological evaluation and molecular modelling of didanosine derivatives

RAVETTI, S.A.; DE CANDIA, C.A.; GUALDESI, S.; PAMPURO, S; TURK, G.; QUEVEDO, M.A.; BRIÑÓN, M.C.

MedChemComm

Royal Society of Chemistry

Año: 2014 vol. 5 p. 622 - 622

2040-2503

ive carbonate derivatives of 50-O-20,30-dideoxyinosine (DDI, 1) have been synthesized by combination with aliphatic alcohols, with their in vitro anti-HIV activity and cytotoxicity being evaluated afterward in human peripheral blood mononuclear cells (PBMCs). One particular compound, namely DDI-Penta, exhibited an outstanding performance because it was found to have both a higher inhibitory potency and a lower cytotoxicity than the lead compound, resulting in a 100 enhancement in its selectivity index. In order to further study this phenomenon, the ability of these derivatives to bind to the cytoplasmatic nucleotidase (ncN-II) was studied by in silico methods. Also, the higher calculated lipophilicity of the synthesized compounds was proposed to improve their permeability through the cell membrane since said lipophilicity would allow a higher concentration of the corresponding prodrug inside the infected cell. Overall, a combination of an optimal lipophilicity and the ability of DDI-P