Natural product-inspired esters and amides of ferulic and caffeic acid as dual inhibitors of HIV-1 reverse transcriptase
SONAR, VIJAY PRAKASH;CORONA, ANGELA;DISTINTO, SIMONA;MACCIONI, ELIAS;MELEDDU, RITA;FOIS, BENEDETTA;FLORIS, COSTANTINO;TRAMONTANO, ENZO;COTTIGLIA, FILIPPO
2017-01-01
Abstract
Using an HIV-1 Reverse Transcriptase (RT)-associated RNase H inhibition assay as lead, bioguided fractionation of the dichloromethane extract of the Ocimum sanctum leaves led to the isolation of five triterpenes (1–5) along with three 3-methoxy-4-hydroxy phenyl derivatives (6–8). The structure of this isolates were determined by 1D and 2D NMR experiments as well as ESI-MS. Tetradecyl ferulate (8) showed an interesting RNase H IC50 value of 12.4 μM and due to the synthetic accessibility of this secondary metabolite, a structure-activity relationship study was carried out. A series of esters and amides of ferulic and caffeic acids were synthesized and, among all, the most active was N-oleylcaffeamide displaying a strong inhibitory activity towards both RT-associated functions, ribonuclease H and DNA polymerase. Molecular modeling studies together with Yonetani-Theorell analysis, demonstrated that N-oleylcaffeamide is able to bind both two allosteric site located one close to the NNRTI binding pocket and the other close to RNase H catalytic site.File | Size | Format | |
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2017 1-s2.0-S0223523417301277-main.pdf Solo gestori archivio
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Pre print Natural Inspired.pdf open access
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