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Updated: Jan 28, 2026

Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors
Published on: April 9, 2014
Aryl Substituted Benzimidazolones as Potent HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors
Nicole Pribut1, Adriaan E Basson2, Willem A L van Otterlo1
1Department of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, 7602 Matieland, Western Cape South Africa.
Abstract:
Since the discovery of HIV as the etiological agent of AIDS, the virus has infected millions of people each year. Fortunately, with the use of HAART, viremia can be suppressed to below detectable levels in the infected individuals, which significantly improves their quality of life and prevents the onset of AIDS. However, HAART is not curative and issues relating to adherence and drug resistance may lead to the re-emergence of viremia, the development of AIDS, and ultimately death. To address a pressing need for the development of new and efficacious antiretroviral agents with activity against viruses bearing prevalent resistant mutations, we have designed two generations of benzimidazolone derivatives as HIV non-nucleoside reverse transcriptase inhibitors. The first generation benzimidazolone inhibitors were found to be potent inhibitors of wild-type HIV reverse transcriptase but were ineffective in the presence of common resistance mutations such as K103N and Y181C. A second generation benzimidazolone inhibitor (compound 42) not only showed inhibitory activity against wild-type HIV but also remained active against HIV containing the K103N, Y181C, and K103N/Y181C drug resistance mutations.
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