From the traditional Chinese medicine plant Schisandra chinensis new scaffolds effective on HIV-1 reverse transcriptase resistant to non-nucleoside inhibitors.
HIV-1 reverse transcriptase (RT) is still an extremely attractive pharmaceutical target for the identification of new inhibitors possibly active on drug resistant strains. Medicinal plants are a rich source of chemical diversity and can be used to identify novel scaffolds to be further developed by chemical modifications. We investigated the ability of the main lignans from Schisandra chinensis (Turcz.) Baill. fruits, commonly used in Traditional Chinese Medicine, to affect HIV-1 RT functions. We purified 6 lignans from Schisandra chinensis fruits and assayed their effects on HIV-1 RT and viral replication. Among the S. chinensis fruit lignans, Schisandrin B and Deoxyschizandrin selectively inhibited the HIV-1 RT-associated DNA polymerase activity. Structure activity relationship revealed the importance of cyclooctadiene ring substituents for efficacy. In addition, Schisandrin B was also able to impair HIV-1 RT drug resistant mutants and the early phases of viral replication. We identified Schisandrin B and Deoxyschizandrin as new scaffold for the further development of novel HIV-1 RT inhibitors.
Institute of Medicinal Plant Development (IMPLAD), 151 Malianwa North Road Haidian District, 100193, Beijing, P. R. China.
Lijia
L
Xu
Nicole
N
Grandi
Claudia
C
Del Vecchio
Daniela
D
Mandas
Angela
A
Corona
Dario
D
Piano
Francesca
F
Esposito
Cristina
C
Parolin
Enzo
E
Tramontano
D019380:Anti-HIV Agents / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D034242:Cyclooctanes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D024921:Drug Resistance, Multiple, Viral; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D005638:Fruit / Q000737:chemistry; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D017705:Lignans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D009154:Mutation; D011083:Polycyclic Compounds / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D032141:Schisandra / Q000737:chemistry*; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D034242:Cyclooctanes; D004365:Drugs, Chinese Herbal; D017705:Lignans; D011083:Polycyclic Compounds; D018894:Reverse Transcriptase Inhibitors; C015499:schizandrin B; C034734:schizandrin A; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase