2. Academic Validation
  3. Synthesis and antitumoral activity of novel analogues monastrol-fatty acids against glioma cells

Synthesis and antitumoral activity of novel analogues monastrol-fatty acids against glioma cells

  • Medchemcomm. 2018 May 30;9(8):1282-1288. doi: 10.1039/c8md00169c.
Franciele S De Oliveira 1,  Patrick M De Oliveira 2,  Luana M Farias 2,  Rafael C Brinkerhoff 2,  Rui Carlos M A Sobrinho 2,  Tamara M Treptow 2,  Caroline R Montes D'Oca 2,  Marcelo A G Marinho 1,  Mariana A Hort 3,  Ana P Horn 1,  Dennis Russowsky 4,  Marcelo G Montes D'Oca 2
Affiliations

Affiliations

  • 1 Programa de Pós-graduação em Ciências Fisiológicas , Instituto de Ciências Biológicas , Universidade Federal do Rio Grande - FURG , Rio Grande , RS , Brazil.
  • 2 Laboratório Kolbe de Síntese Orgânica , Universidade Federal do Rio Grande - FURG , Rio Grande , RS , Brazil . Email: dqmdoca@furg.br ; ; Tel: +55 53 32336960.
  • 3 Laboratório de Ensaios Farmacológicos e Toxicológicos , Instituto de Ciências Biológicas , Universidade Federal do Rio Grande - FURG , Rio Grande , RS , Brazil.
  • 4 Laboratório de Sínteses Orgânicas , Instituto de Química , Universidade Federal do Rio Grande do Sul , Av. Bento Gonçalves 9500 , 91501-970 , Porto Alegre , RS , Brazil.
PMID: 30151081 DOI: 10.1039/c8md00169c
Abstract

Monastrol is a small cell-permeable heterocyclic molecule that is recognized as an inhibitor of mitotic Kinesin Eg5. Heterocyclic-fatty acid derivatives are a new class of compounds with a broad range of biological activities. This work describes a comparative study of the in vitro antitumoral activity of a series of new long-chain monastrol analogues against rat glioblastoma cells. The novel analogues C6-substituted monastrol and oxo-monastrol were synthesized via Biginelli multicomponent condensation of fatty β-ketoester in good yields using a simple approach catalyzed by nontoxic and free-metal sulfamic acid. Following synthesis, their in vitro antitumoral activities were investigated. Notably, all analogues tested were active against rat glioblastoma cells. Superior activity was observed by analogues derived from palmitic and stearic fatty acid chains; these compounds were the most potent molecules, showing 13-fold higher potency than monastrol with IC50 values of 5.11 and 6.85 μM, respectively. These compounds could provide promising new lead derivatives for more potent antitumor drugs.

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