Novel hybrid DHPM-fatty acids: Synthesis and activity against glioma cell growth in vitro

We described the first synthesis of fatty acid 3,4-dihydropyrimidinones (DHPM-fatty acids) using the Biginelli multicomponent reaction. Antiproliferative activity on two glioma cell lines (C6 rat and U-138-MG human) was also reported. The novel DHPM-fatty acids reduced glioma cell viability relative...

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Bibliographic Details
Published in:European journal of medicinal chemistry 2015-05, Vol.95, p.552-562
Main Authors: Treptow, Tamara G.M., Figueiró, Fabrício, Jandrey, Elisa H.F., Battastini, Ana M.O., Salbego, Christianne G., Hoppe, Juliana B., Taborda, Priscila S., Rosa, Sabrina B., Piovesan, Luciana A., Montes D'Oca, Caroline Da R., Russowsky, Dennis, Montes D'Oca, Marcelo G.
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Antiproliferative activity
Cell Line, Tumor
Cell Proliferation - drug effects
Chemistry Techniques, Synthetic
Drug Design
Fatty acids
Fatty Acids - chemical synthesis
Fatty Acids - chemistry
Fatty Acids - pharmacology
Glioma - pathology
Glioma cell
Humans
Male
Monastrol
Oil chemistry
Rats
Rats, Wistar
Uridine - analogs & derivatives
Uridine - chemistry
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Summary:We described the first synthesis of fatty acid 3,4-dihydropyrimidinones (DHPM-fatty acids) using the Biginelli multicomponent reaction. Antiproliferative activity on two glioma cell lines (C6 rat and U-138-MG human) was also reported. The novel DHPM-fatty acids reduced glioma cell viability relative to temozolomide. Hybrid oxo-monastrol-palmitic acid was the most potent, reducing U-138-MG human cell viability by ca. 50% at 10 μM. In addition, the DHPM-fatty acids showed a large safety range to neural cells, represented by the organotypic hippocampal culture. These results suggest that the increased lipophilicity of DHPM-fatty acids offer a promising approach to overcoming resistance to chemotherapy and may play an important role in the development of new antitumor drugs. [Display omitted] •Synthesis and antiproliferative activity of new DHPM-fatty acids.•DHPM-fatty acids reduced glioma cell viability relative to temozolomide.•DHPM-fatty acids could represent prototypes of new antitumor drugs.
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2015.03.062