Biological evaluation and molecular modelling of didanosine derivatives.

SOLEDAD RAVETTI, CRISTIAN A. DE CANDIA, MARÍA S. GUALDESI, SANDRA PAMPURO, GABRIELA TURK, MARIO A. QUEVEDO AND MARGARITA C. BRIÑÓN.

MedChemComm

Royal Society of Chemistry.

Año: 2014 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 50- 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 D