Potential Inhibitors of the Activity of the Cholesterol-Ester Transfer Protein

TARRAGA, WILSON; GARDA, H.; JUAN D. TOLEDO; GONZALEZ MARINA CECILIA

JOURNAL OF COMPUTATIONAL BIOLOGY

MARY ANN LIEBERT INC

Lugar: New York; Año: 2019 vol. 26 p. 1 - 12

1066-5277

The cholesterol-ester transfer protein (CETP) exchanges lipids between high-density lipoproteins(HDLs) and low-density lipoproteins (LDLs). The excessive transport of lipids from HDLs to LDLs mediated by this protein can cause an alteration in the deposition of lipoproteins onto the arterial walls, thus promoting the development of arteriosclerosis. DifferentCETP inhibitorshave been tested in recent years, but none has been confirmed as being effectively palliative for the disease. We employed in silico databases and molecular docking as a computational methodto predict how potential CETP inhibitors could interact with the active site of the CETP protein. Upon previously comparing two computer software packages to determine which generated a greater number of accurate CETP-inhibitor?complex structures, we chose the more appropriate program for our studies. We then abstracted a series of databases of known CETPinhibitors and noninhibitors exhibiting different 50% concentrations of CETP-inhibitory (INH) activity, to generate virtual structures for docking with different combinations of the CETP receptor. From this process, we obtained as the most suitable structure 4F2A_1OB_C_PCW?it accordingly having a greater area under the receiver operating characteristic curve. The molecular docking of known compounds in comparison with the respective conformation of this inhibitor enabled us to obtain DGs (in kcal/mol) from which data we made a first exploration of unknown compounds for CETP-INH activity. Thus, the 4F2A_1OB_C_PCWstructure was docked with DrugBank-Approved commercial compounds in an extensivedatabase, whose status had already been established from pharmacokinetics and toxicology.In this study, we present a group of potential compounds as CETP-inhibitor candidates.