A pharmaceutical compound for targeted cancer therapy using nucleobase analog derivatives with omega-3 fatty acids

The invention describes compounds combining nucleobase analogs with omega-3 fatty acids, enhancing cancer treatment efficacy, particularly for pancreatic cancer. These compounds improve stability and solubility and demonstrate significant anti-cancer activity, offering potential for targeted therapy.

Background

Pancreatic cancer presents a significant challenge in oncology due to its high mortality rate and poor prognosis, with survival rates remaining dismally low despite advancements in medical science. The disease is often diagnosed at an advanced stage, limiting the effectiveness of surgical interventions.

Current treatment options primarily involve chemotherapy, with gemcitabine being a standard choice. However, gemcitabine's efficacy is hampered by rapid deamination and limited cellular uptake, necessitating high doses that can lead to severe side effects. Additionally, the hydrophilic nature of gemcitabine restricts its ability to penetrate cell membranes efficiently, further reducing its therapeutic potential.

Efforts to enhance the drug's effectiveness have included combination therapies and the development of analogues, but these approaches have yielded limited success. The incorporation of polyunsaturated fatty acids, known for their anti-inflammatory and potential anticancer properties, into therapeutic strategies has been explored, but challenges remain in achieving stable and effective drug formulations that can improve patient outcomes in pancreatic cancer treatment.

Technology description

The technology involves the creation of compounds that combine nucleobase analogs with omega-3 polyunsaturated fatty acids, specifically designed for cancer treatment, with a focus on pancreatic cancer. These compounds, which can exist as pharmaceutically acceptable salts or prodrugs, include purine and pyrimidine analogs, with gemcitabine being a notable example. The omega-3 fatty acids used include docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). The synthesis process, such as the formation of 4-(N)-docosahexaenoyl gemcitabine, enhances the stability and solubility of these compounds. They exhibit significant anti-proliferative, cytotoxic, and pro-apoptotic activities against various cancer cell lines in vitro and have shown effective tumor inhibition in animal models. The technology also explores the pharmacokinetics and biodistribution of these compounds, highlighting their potential for targeted cancer therapy.

This technology is differentiated by its innovative approach of combining nucleobase analogs with omega-3 fatty acids, which enhances the therapeutic efficacy of traditional cancer treatments like gemcitabine. The conjugation of these compounds not only improves their stability and solubility but also significantly increases their cytotoxicity against cancer cells compared to gemcitabine alone. The use of omega-3 fatty acids, known for their anti-inflammatory and potential anti-cancer properties, adds a novel dimension to cancer treatment, potentially reducing side effects and improving patient outcomes. Additionally, the targeted delivery and enhanced biodistribution of these compounds to tumor sites offer a promising advancement in precision oncology, potentially leading to more effective and less toxic cancer therapies.

Benefits

Enhanced stability and solubility of chemotherapeutic compounds
Significant anti-proliferative, cytotoxic, and pro-apoptotic activities against various cancer cell lines in vitro
Effective tumor inhibition demonstrated in animal models
Potential for targeted cancer therapy, particularly for pancreatic cancer
Improved pharmacokinetics and biodistribution for better therapeutic outcomes