Combretastatin A-4 (CA-4) is a highly cytotoxic natural product and several derivatives have been prepared which underwent clinical trial. These investigations revealed that the cis-stilbene moiety of the natural product is prone to undergo cis/trans isomerization under physiological conditions, reducing the overall activity of the drug candidates. Herein, we report the preparation of cis-restrained carbocyclic analogs of CA-4. The compounds, which differ by the size and hybridization of the carbocyclic ring have been evaluated for their cytotoxic properties and their ability to inhibit tubulin polymerization. Biological data, supported by molecular docking studies, identified cyclobutenyl and cyclobutyl derivatives of the natural product as highly promising drug candidates.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmc.2019.07.048 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A conifer metabolite corrects episodic ataxia type 1 by voltage sensor-mediated ligand activation of Kv1.1.
Proc Natl Acad Sci U S A
January 2025
Bioelectricity Laboratory, Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA 92697.
Loss-of-function sequence variants in , which encodes the voltage-gated potassium channel Kv1.1, cause Episodic Ataxia Type 1 (EA1) and epilepsy. Due to a paucity of drugs that directly rescue mutant Kv1.
View Article and Find Full Text PDFGenesis and regulation of C-terminal cyclic imides from protein damage.
Proc Natl Acad Sci U S A
January 2025
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138.
C-Terminal cyclic imides are posttranslational modifications that can arise from spontaneous intramolecular cleavage of asparagine or glutamine residues resulting in a form of irreversible protein damage. These protein damage events are recognized and removed by the E3 ligase substrate adapter cereblon (CRBN), indicating that these aging-related modifications may require cellular quality control mechanisms to prevent deleterious effects. However, the factors that determine protein or peptide susceptibility to C-terminal cyclic imide formation or their effect on protein stability have not been explored in detail.
View Article and Find Full Text PDFComplex tissue regeneration in reveals a phylogenetic signal for enhanced regenerative ability in deomyine rodents.
Proc Natl Acad Sci U S A
January 2025
Department of Biology, University of Kentucky, Lexington, KY 40508.
Identifying why complex tissue regeneration is present or absent in specific vertebrate lineages has remained elusive. One also wonders whether the isolated examples where regeneration is observed represent cases of convergent evolution or are instead the product of phylogenetic inertia from a common ancestral program. Testing alternative hypotheses to identify genetic regulation, cell states, and tissue physiology that explain how regenerative healing emerges in some species requires sampling multiple species among which there is variation in regenerative ability across a phylogenetic framework.
View Article and Find Full Text PDFImmunoinformatics design of a novel multiepitope vaccine candidate against non-typhoidal salmonellosis caused by Salmonella Kentucky using outer membrane proteins A, C, and F.
PLoS One
January 2025
Foot and Mouth Disease Department, National Veterinary Research Institute, Vom, Plateau State, Nigeria.
The global public health risk posed by Salmonella Kentucky (S. Kentucky) is rising, particularly due to the dissemination of antimicrobial resistance genes in human and animal populations. This serovar, widespread in Africa, has emerged as a notable cause of non-typhoidal gastroenteritis in humans.
View Article and Find Full Text PDFBushen-Huoxue-Mingmu-Formula attenuates pressurization-induced retinal ganglion cell damage by reducing mitochondrial autophagy through the inhibition of the Pink1/Parkin pathway.
Medicine (Baltimore)
January 2025
Opthalmology, Chongqing Hechuan District People's Hospital, Chongqing, China.
Background: Bushen-Huoxue-Mingmu-Formula (MMF) has achieved definite clinical efficacy. However, its mechanism is still unclear.
Objective: Investigating the molecular mechanism of MMF to protect retinal ganglion cells (RGCs).
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!