Background
The emergence of drug resistant HIV strains and suitability of NNRTIs as potent anti-HIV molecules used in HAART did attract our attention towards developing NNRTIs. We, therefore, focused on developing some new NNRTIs utilizing benzimidazole and pyrimidine moieties to match the hydrophobic nature of the allosteric pocket in HIV-RT.
Methods
Compounds designed on the basis of extensive computational studies, were finally synthesized through facile synthetic route and characterized using various chromatographic and spectral techniques. All synthesized molecules have been screened against HIV-1 using TZM bl assay and laboratory adapted strains HIV-1 IIIB (X4, subtype B), HIV-1 Ada5 (R5, Subtype B) and the primary isolates HIV-1UG070 (X4, Subtype D).
Results
Cell based assay showed that majority of the compounds were active at micro molar concentrations (1.39-17.39 µM) and the SI value ranged between 10.77-17.39 against lab adapted strains and 5.8–13.91 against primary isolates. The studies on structure–activity relationship were also consistent with the experimental data.
Conclusions
In view of the results obtained, these compounds may be developed as potent inhibitors of HIV-1 replication with suitable structural/pharmacophore modifications.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (
http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (
http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.