Neoflavonoids as Inhibitors of HIV-1 Replication by Targeting the Tat and NF-κB Pathways
Dionisio A. Olmedo,
José Luis López-Pérez,
Esther del Olmo,
Luis M. Bedoya,
Rocío Sancho,
José Alcamí,
Eduardo Muñoz,
Arturo San Feliciano,
Mahabir P. Gupta
Affiliations
Dionisio A. Olmedo
Pharmaceutical Chemistry Area, Department of Pharmaceutical Sciences, University of Salamanca, Faculty of Pharmacy, CIETUS, IBSAL, Campus Miguel de Unamuno, 37007 Salamanca, Spain
José Luis López-Pérez
Pharmaceutical Chemistry Area, Department of Pharmaceutical Sciences, University of Salamanca, Faculty of Pharmacy, CIETUS, IBSAL, Campus Miguel de Unamuno, 37007 Salamanca, Spain
Esther del Olmo
Pharmaceutical Chemistry Area, Department of Pharmaceutical Sciences, University of Salamanca, Faculty of Pharmacy, CIETUS, IBSAL, Campus Miguel de Unamuno, 37007 Salamanca, Spain
Luis M. Bedoya
National Centre of Microbiology, Institute Carlos III, Crt. Majadahonda a Pozuelo, 28220 Majadahonda, Madrid, Spain
Rocío Sancho
Department of Cellular Biology, Physiology and Immunology, University of Córdoba, Faculty of Medicine Avda de Menendez Pidal s/n, 14004 Córdoba, Spain
José Alcamí
National Centre of Microbiology, Institute Carlos III, Crt. Majadahonda a Pozuelo, 28220 Majadahonda, Madrid, Spain
Eduardo Muñoz
Department of Cellular Biology, Physiology and Immunology, University of Córdoba, Faculty of Medicine Avda de Menendez Pidal s/n, 14004 Córdoba, Spain
Arturo San Feliciano
Pharmaceutical Chemistry Area, Department of Pharmaceutical Sciences, University of Salamanca, Faculty of Pharmacy, CIETUS, IBSAL, Campus Miguel de Unamuno, 37007 Salamanca, Spain
Mahabir P. Gupta
CIFLORPAN, Center for Pharmacognostic Research on Panamanian Flora, College of Pharmacy, University of Panama, P.O. Box 0824-00172 Panama, Panama
Twenty-eight neoflavonoids have been prepared and evaluated in vitro against HIV-1. Antiviral activity was assessed on MT-2 cells infected with viral clones carrying the luciferase reporter gene. Inhibition of HIV transcription and Tat function were tested on cells stably transfected with the HIV-LTR and Tat protein. Seven 4-phenylchromen-2-one derivatives showed HIV transcriptional inhibitory activity but only the phenylchrome-2-one 10 inhibited NF-κB and displayed anti-Tat activity simultaneously. Compounds 10, 14, and 25, inhibited HIV replication in both targets at concentrations <25 μM. The assays of these synthetic 4-phenylchromen-2-ones may aid in the investigation of some aspects of the anti-HIV activity of such compounds and could serve as a scaffold for designing better anti-HIV compounds, which may lead to a potential anti-HIV therapeutic drug.
