title: Novel Cyclopropyl-Indole Derivatives as HIV Non-Nucleoside Reverse Transcriptase Inhibitors.
abstract: The HIV pandemic represents one of the most serious diseases to face mankind in both a social and economic context, with many developing nations being the worst afflicted. Due to ongoing resistance issues associated with the disease, the design and synthesis of anti-HIV agents presents a constant challenge for medicinal chemists. Utilizing molecular modeling, we have designed a series of novel cyclopropyl indole derivatives as HIV non-nucleoside reverse transcriptase inhibitors and carried out their preparation. These compounds facilitate a double hydrogen bonding interaction to Lys101 and efficiently occupy the hydrophobic pockets in the regions of Tyr181/188 and Val179. Several of these compounds inhibited HIV replication as effectively as nevirapine when tested in a phenotypic assay.
authors.affiliation: Department of Chemistry and Polymer Science, Stellenbosch University , Western Cape, South Africa.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Hassam
authors.affiliation: National Institute for Communicable Diseases , Johannesburg, South Africa.
authors.forename: Adriaan E
authors.initials: AE
authors.lastname: Basson
authors.affiliation: Department of Chemistry, Emory University , Atlanta, Georgia, United States.
authors.forename: Dennis C
authors.initials: DC
authors.lastname: Liotta
authors.affiliation: National Institute for Communicable Diseases , Johannesburg, South Africa.
authors.forename: Lynn
authors.initials: L
authors.lastname: Morris
authors.affiliation: Department of Chemistry and Polymer Science, Stellenbosch University , Western Cape, South Africa.
authors.forename: Willem A L
authors.initials: WA
authors.lastname: van Otterlo
authors.affiliation: Department of Chemistry and Polymer Science, Stellenbosch University , Western Cape, South Africa.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Pelly
keywords: HIV; NNRTI; cyclopropyl; indole; rational design