In this paper we describe the preparation of some biphenylquinuclidine derivatives and their evaluation as inhibitors of squalene synthase in order to explore their potential in the treatment of the parasitic diseases leishmaniasis and Chagas disease. The compounds were screened against recombinant Leishmania major squalene synthase and against Leishmania mexicana promastigotes, Leishmania donovani intracellular amastigotes and Trypanosoma cruzi intracellular amastigotes. Compounds that inhibited the enzyme, also reduced the levels of steroids and caused growth inhibition of L. mexicana promastigotes. However there was a lower correlation between inhibition of the enzyme and growth inhibition of the intracellular parasites, possibly due to delivery problems. Some compounds also showed growth inhibition of T. brucei rhodesiense trypomastigotes, although in this case alternative modes of action other than inhibition of SQS are probably involved.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmc.2005.02.060 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Mechanism of sodium nitroprusside regulating ginseng quality.
Sci Rep
January 2025
Department of Pharmacognosy, Heilongjiang University of Chinese Medicine, Harbin, 150040, Hei-longjiang, China.
The roots of Panax ginseng C. A. Meyer (ginseng) are one of the traditional medicinal herbs in Asian countries and is known as the "king of all herbs".
View Article and Find Full Text PDFSynthetic inhibition of SREBP2 and the mevalonate pathway blocks rhabdomyosarcoma tumor growth in vitro and in vivo and promotes chemosensitization.
Mol Metab
December 2024
Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy. Electronic address:
Article Synopsis
- The study aimed to explore the effects of targeting the mevalonate pathway (MVP) in rhabdomyosarcoma (RMS), a common soft tissue tumor in young individuals.
- In silico analyses showed that higher levels of MVP-related genes correlated with poorer patient survival, while in vitro tests revealed that MVP inhibitors significantly reduced RMS cell growth, migration, and survival.
- In vivo experiments demonstrated the effectiveness of MVP inhibition in RMS xenografts, highlighting the potential of these inhibitors as a therapeutic strategy against RMS.
Discovery and Functional Identification of 2,3-Oxidosqualene Cyclases and Cytochrome P450s in Triterpenoid Metabolic Pathways of .
J Agric Food Chem
December 2024
Guangdong Engineering Research Center of Biosynthesis and Metabolism of Effective Components of Chinese Medicine, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, P. R. China.
Article Synopsis
- * The study identified key enzyme genes involved in the triterpenoid metabolic pathways using transcriptome sequencing and synthetic biology, particularly focusing on two 2,3-oxidosqualene cyclases and two cytochrome P450s.
- * Researchers successfully reconstructed the biosynthetic pathway for ursane and oleanane-type triterpenoids in a yeast host, detailing the enzymatic reactions necessary for producing important compounds like ursolic acid and oleanolic acid.
Structure-based virtual screening to identify hypocholesterolemic phytochemicals as potent inhibitors of squalene synthase a potential target for hypercholesterolemia.
J Biomol Struct Dyn
December 2024
Laboratory of Biology and Health, Faculty of Sciences Ben M'Sick, Health and Biotechnology Research Centre, Hassan II University of Casablanca, Casablanca, Morocco.
Squalene synthase (SQS) plays a crucial role in the cholesterol biosynthetic pathway. Its distinctive strategic position makes it a promising candidate for targeting and developing new anti-hypercholesterolemic agents. To uncover novel phytochemical scaffolds as potential inhibitors of SQS, we employed a structure-based virtual screening approach that involves screening 545 phytochemicals collected from Moroccan aromatic and medicinal plants and filtering them based on RMSD values and their affinity towards the target enzyme.
View Article and Find Full Text PDFEffects of water stress on secondary metabolism of Panax ginseng fresh roots.
PLoS One
November 2024
Department of Pharmacognosy, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China.
Article Synopsis
- Panax ginseng, a commonly used herbal medicine in Asia, relies on its roots and rhizomes, which contain ginsenosides, the main active compounds that enhance its adaptability to ecological stress.
- A study involved applying water spray to create a short-term water stress scenario for 5-year-old P. ginseng roots, revealing significant increases in oxidative stress indicators and enzyme activities linked to ginsenoside production.
- The water stress treatment resulted in notable boosts in various ginsenosides (e.g., Rg1 and Rb1) and a 40.1% increase in total saponins, highlighting the potential for water management to enhance the medicinal properties of P. ginseng.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!