Related Experiment Video
Updated: Jan 23, 2026
MR Molecular Imaging of Prostate Cancer with a Small Molecular CLT1 Peptide Targeted Contrast Agent
Published on: September 3, 2013
Synthesis, Anticancer Activity on Prostate Cancer Cell Lines and Molecular Modeling Studies of Flurbiprofen-Thioether
Özgür Yılmaz1, Burak Bayer2, Hatice Bekçi3
1TUBITAK Marmara Research Center, Materials Institute, Kocaeli, Turkey.
Background:
Prostate cancer is still one of the serious causes of mortality and morbidity in men. Despite recent advances in anticancer therapy, there is a still need of novel agents with more efficacy and specificity in the treatment of prostate cancer. Because of its function on angiogenesis and overexpression in the prostate cancer, methionine aminopeptidase-2 (MetAP-2) has been a potential target for novel drug design recently.
Objective:
A novel series of Flurbiprofen derivatives N-(substituted)-2-(2-(2-fluoro-[1,1'- biphenyl]-4-il)propanoyl)hydrazinocarbothioamide (3a-c), 4-substituted-3-(1-(2-fluoro-[1,1'-biphenyl]- 4-yl)ethyl)-1H-1,2,4-triazole-5(4H)-thione (4a-d), 3-(substitutedthio)-4-(substituted-phenyl)- 5-(1-(2-fluoro-[1,1'-biphenyl]-4-yl)ethyl)-4H-1,2,4-triazole (5a-y) were synthesized. The purpose of the research was to evaluate these derivatives against MetAP-2 in vitro and in silico to obtain novel specific and effective anticancer agents against prostate cancer.
Methods:
The chemical structures and purities of the compounds were defined by spectral methods (1H-NMR, 13C-NMR, HR-MS and FT-IR) and elemental analysis. Anticancer activities of the compounds were evaluated in vitro by using MTS method against PC-3 and DU-143 (androgenindependent human prostate cancer cell lines) and LNCaP (androgen-sensitive human prostate adenocarcinoma) prostate cancer cell lines. Cisplatin was used as a positive sensitivity reference standard.
Results:
Compounds 5b and 5u; 3c, 5b and 5y; 4d and 5o showed the most potent biological activity against PC3 cancer cell line (IC50= 27.1 μM, and 5.12 μM, respectively), DU-145 cancer cell line (IC50= 11.55 μM, 6.9 μM and 9.54 μM, respectively) and LNCaP cancer cell line (IC50= 11.45 μM and 26.91 μM, respectively). Some compounds were evaluated for their apoptotic caspases protein expression (EGFR/PI3K/AKT pathway) by Western blot analysis in androgen independent- PC3 cells. BAX, caspase 9, caspsase 3 and anti-apoptotic BcL-2 mRNA levels of some compounds were also investigated. In addition, molecular modeling studies of the compounds on MetAP-2 enzyme active site were evaluated in order to get insight into binding mode and energy.
Conclusion:
A series of Flurbiprofen-thioether derivatives were synthesized. This study presented that some of the synthesized compounds have remarkable anticancer and apoptotic activities against prostate cancer cells. Also, molecular modeling studies exhibited that there is a correlation between molecular modeling and anticancer activity results.
Insights
Researchers synthesized novel Flurbiprofen derivatives to target methionine aminopeptidase-2 (MetAP-2) for prostate cancer treatment. Some compounds demonstrated significant anticancer and apoptotic activity in vitro and in silico, showing promise as new therapeutic agents.
Area of Science:
- Medicinal Chemistry
- Oncology
- Molecular Biology
Background:
- Prostate cancer remains a significant cause of mortality in men, necessitating novel therapeutic agents.
- Methionine aminopeptidase-2 (MetAP-2) is overexpressed in prostate cancer and plays a role in angiogenesis, making it a potential drug target.
- Current anticancer therapies require complementary agents with enhanced efficacy and specificity.
Purpose of the Study:
- Synthesize and evaluate novel Flurbiprofen derivatives as potential anticancer agents targeting MetAP-2.
- Assess the in vitro and in silico anticancer activity of synthesized compounds against various prostate cancer cell lines.
- Identify specific derivatives with potent activity and favorable binding interactions with MetAP-2.
Main Methods:
- Synthesis of novel Flurbiprofen derivatives, including N-(substituted)-2-(2-(2-fluoro-[1,1'- biphenyl]-4-il)propanoyl)hydrazinocarbothioamide, triazole-thiones, and triazole-thioethers.
- Characterization of synthesized compounds using spectral methods (NMR, HR-MS, FT-IR) and elemental analysis.
- In vitro evaluation of anticancer activity against PC-3, DU-145, and LNCaP prostate cancer cell lines using MTS assay, with cisplatin as a positive control.
- In silico molecular modeling studies to investigate binding interactions with the MetAP-2 enzyme active site.
Main Results:
- Several synthesized Flurbiprofen derivatives exhibited potent in vitro anticancer activity against PC-3, DU-145, and LNCaP cell lines, with specific compounds showing low IC50 values.
- Compounds 5b, 5u, 3c, 5y, 4d, and 5o demonstrated significant cytotoxic effects on prostate cancer cells.
- Western blot analysis indicated that some compounds induced apoptosis by modulating apoptotic caspases and related proteins (e.g., BAX, caspase 9, caspase 3, Bcl-2) via the EGFR/PI3K/AKT pathway.
- Molecular modeling studies revealed a correlation between the binding affinity of compounds to MetAP-2 and their observed anticancer activity.
Conclusions:
- A novel series of Flurbiprofen-thioether derivatives were successfully synthesized.
- The synthesized compounds demonstrated significant anticancer and apoptotic activities against prostate cancer cells.
- Molecular modeling studies support the observed anticancer effects, suggesting a correlation between binding interactions and biological activity, highlighting potential for developing targeted prostate cancer therapies.
Related Concept Videos
02:00Molecular Models
01:16Types of Potential Energy
02:58Cell Potential and Free Energy
Thermodynamics is the branch of physics dealing with the relationship between heat and other forms of energy. In an electrochemical cell, chemical energy is converted into electrical energy.
Thus, a link can be predicted between cell potential, free energy change, and the equilibrium constant for the reaction. Cell potential can also be measured as the oxidant or the reducing strength, and similar acid-base strength measures are reflected in equilibrium...
02:43Mouse Models of Cancer Study
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...
01:16Cell Lines
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...