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Development of potent CPP6–gemcitabine conjugates against human prostate cancer cell line (PC-3)
- Source :
- RSC Med Chem
- Publication Year :
- 2020
- Publisher :
- Royal Society of Chemistry (RSC), 2020.
-
Abstract
- Gemcitabine (dFdC) is a nucleoside analogue used in the treatment of various cancers, being a standard treatment for advanced pancreatic cancer. The effect of gemcitabine is severely compromised due to its rapid plasma degradation, systemic toxicity and drug resistance, which restricts its therapeutic efficacy. Our main goal was to develop new active conjugates of dFdC with novel cell-penetrating hexapeptides (CPP6) to facilitate intracellular delivery of this drug. All new peptides were prepared by solid phase peptide synthesis (SPPS), purified and characterized by HPLC and LC-MS. Cell-penetrating peptides (CPP) contain a considerably high ratio of positively charged amino acids, imparting them with cationic character. Tumor cells are characterized by an increased anionic nature of their membrane surface, a property that could be used by CPP to target these cells. The BxPC-3, MCF-7 and PC-3 cancer cell lines were used to evaluate the in vitro cytotoxicity of conjugates and the results showed that conjugating dFdC with CPP6 significantly enhanced cell growth inhibitory activity on PC-3 cells, with IC(50) between 14 and 15 nM. These new conjugates have potential to become new therapeutic tools for cancer therapy.
- Subjects :
- Pharmaceutical Science
02 engineering and technology
01 natural sciences
Biochemistry
chemistry.chemical_compound
Pancreatic cancer
Drug Discovery
medicine
Peptide synthesis
IC50
Pharmacology
chemistry.chemical_classification
Nucleoside analogue
010405 organic chemistry
Chemistry
Cell growth
Organic Chemistry
021001 nanoscience & nanotechnology
medicine.disease
Gemcitabine
0104 chemical sciences
Amino acid
Cancer research
Molecular Medicine
0210 nano-technology
Intracellular
medicine.drug
Subjects
Details
- ISSN :
- 26328682
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- RSC Medicinal Chemistry
- Accession number :
- edsair.doi.dedup.....6bc485445d68c5e6381099f756502fc8