Halolactones are potent HIV-1 non-nucleoside reverse transcriptase inhibitors

Herein, we report the discovery of halolactone derivatives as efficient non-nucleoside reverse transcriptase inhibitors (NNRTIs) and the study of their structure-activity relationships (SARs). Among the various halolactone derivatives, 5-exo lactone 3-(chloro(2-chlorophenyl)-methyl)isobenzofuran-1(3H)-one 13a showed excellent potency against WT HIV-1 in the reverse transcriptase gene with a low EC50 value of 0.45 mu M. In most of the cases, the property and the position of the substituents had a definite effect on the activities of anti-HIV-1 activity. In contrast, the 6-endo lactones (isochroman-1-ones) had inferior inhibitory activities against HIV-1. This work offered a structurally simple scaffold (isobenzofuran-1(3H)-one) for the development of novel anti-HIV drugs.