Biological evaluation of quinoxaline compounds as anti-hiv agents targeting reverse transcriptase enzyme

LUCAS FABIAN; ALBERTINA MOGLIONI; EMILIANO BARRIONUEVO; GABRIELA TURK; MARISA TAVERNA PORRO; MELINA SALVATORI; FLORENCIA MARTINI

Mar del Plata

Congreso; Reunion Anual de Sociedades de Biociencia 2019; 2019

SAIC-SAFE-SAB-SAP-AACyTAL-Nanomed-ar

INTRODUCTION:Infections by HIV still represents a global threat to human health. Due to appearance of multi-resistant virus strains, the poor compliance of treatments and the adverse side effects of the therapy, development of new treatment agents is still required. Quinoxaline derivatives have shown, among other activities, high potency in the inhibition of HIV reverse transcriptase (RT) and HIV replication in cell culturePreviously, a chemical library of quinoxaline derivatives was constructed and screened using docking and 3D-QSAR model. 25 compounds of the library were synthezised. Here we present the results of their biological activity evaluation.OBJECTIVE:The aim of this work was the discovery of new RT inhibitors containing a quinoxaline scaffoldCONCLUSION:Twenty-five quinoxaline compounds were selected for synthesis from the filter process of a chemical library, and according to their chemical synthetic simplicity. Then, they were prepared and evaluated as inhibitors of the recombinant RT enzyme. Among the synthesized compounds, compound 3 demonstrated potent in-vitro inhibitory activity towards HIV RT, only slightly weaker than commercial NVP, currently used in the clinic. When these compounds were evaluated in HIV infected cells, two compounds 3 and 12, showed promising anti-HIV activity. Compound 3 had similar anti-HIV and cytotoxicity profiles than commercial NVP while compound 12 was less active against the virus in infected cells. Further development of 3 (lead compound) and 12 (hit compound) will likely provide novel and more potent RT inhibitors for HIV treatment.