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Synthesis and evaluation of A-seco type triterpenoids for anti-HIV-1protease activity
- Source :
- European Journal of Medicinal Chemistry. 44:4112-4120
- Publication Year :
- 2009
- Publisher :
- Elsevier BV, 2009.
-
Abstract
- 2,3-Seco-dioic acids derived from four different triterpene skeletons were prepared and evaluated for their anti-HIV-1 protease activity. Two A-seco derivatives showed potent inhibitory activity against HIV-1 protease (3c and 3e, IC(50) 5.7 and 3.9 microM, respectively), while four other derivatives showed moderate to weak inhibition (3a, 3b, 3d and 3f, IC(50) 15.7-88.1 microM). The combination of a 2,3-seco-2,3-dioic acid functional group in ring A and a free acid group at C-28 or C-30 significantly enhanced HIV-1 protease inhibitory activity (3a, 3c-3e, IC(50) 3.9-17.6 microM). On the other hand, all A-seco derivatives were found to be very weak inhibitors of HCV, renin and trypsin proteases (IC(50)>80 microM). These findings indicate that A-seco triterpenes with a carboxyl group at C-28 or C-30 are novel and highly selective HIV-1 protease inhibitors.
- Subjects :
- Proteases
Anti-HIV Agents
Stereochemistry
medicine.medical_treatment
HIV Infections
Hepacivirus
Structure-Activity Relationship
HIV Protease
HIV-1 protease
Triterpene
Renin
Drug Discovery
medicine
Protease inhibitor (pharmacology)
Pharmacology
chemistry.chemical_classification
Protease
biology
Chemistry
Organic Chemistry
HIV Protease Inhibitors
General Medicine
Trypsin
Triterpenes
Enzyme
Biochemistry
Enzyme inhibitor
HIV-1
biology.protein
medicine.drug
Subjects
Details
- ISSN :
- 02235234
- Volume :
- 44
- Database :
- OpenAIRE
- Journal :
- European Journal of Medicinal Chemistry
- Accession number :
- edsair.doi.dedup.....bdeb1576cfe044f628e8a57af1e4eccc