Novel R-(+)-limonene-based thiosemicarbazones and their antitumor activity against human tumor cell lines

  • Eur J Med Chem. 2014 May 22:79:110-6. doi: 10.1016/j.ejmech.2014.03.086.
Fábio Vandresen  1 ,  Hugo Falzirolli  2 ,  Sabrina A Almeida Batista  2 ,  Ana Paula B da Silva-Giardini  2 ,  Diogo N de Oliveira  3 ,  Rodrigo R Catharino  3 ,  Ana Lúcia T G Ruiz  4 ,  João E de Carvalho  4 ,  Mary Ann Foglio  4 ,  Cleuza Conceição da Silva  5
Affiliations
  • 1. Departamento de Química, Centro de Ciências Exatas, Universidade Estadual de Maringá, Av. Colombo, 5790, CEP 87020-900, Maringá, PR, Brazil. Electronic address: [email protected].
  • 2. Departamento de Química, Centro de Ciências Exatas, Universidade Estadual de Maringá, Av. Colombo, 5790, CEP 87020-900, Maringá, PR, Brazil.
  • 3. Faculdade de Ciências Médicas, Universidade Estadual de Campinas, CEP 13083-877, Campinas, SP, Brazil.
  • 4. Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas (CPQBA), Universidade Estadual de Campinas, 6171, CEP 13083-970, Campinas, SP, Brazil.
  • 5. Departamento de Química, Centro de Ciências Exatas, Universidade Estadual de Maringá, Av. Colombo, 5790, CEP 87020-900, Maringá, PR, Brazil. Electronic address: [email protected].
PMID: 24727464 DOI: 10.1016/j.ejmech.2014.03.086
Abstract

In an attempt to develop potent and selective antitumor agents, a series of novel thiosemicarbazones derived from a natural monoterpene R-(+)-limonene was synthesized and their antitumor activity was evaluated. Overall, the majority of tested compounds exhibited considerable inhibitory effects on the growth of a wide range of Cancer cell lines. Almost all of tested thiosemicarbazones were especially sensitive to prostate cells (PC-3). Derivatives 5, 6, 8, 9, 10, 11 and 13 presented the most potent antitumor activity against PC-3 cells. These compounds showed lower value of GI50 (0.04-0.05 μM) than the reference drug paclitaxel, besides a high selectivity for the same cell line. The 4-fluorobenzaldehyde derivative 10 was the most selective compound for prostate cells, while 2-hydroxybenzaldehyde derivative 8 was the most active compound, with potent antitumor activity against all tested cell lines.

Keywords
Antitumor; Prostate cancer cells; R-(+)-limonene; Thiosemicarbazide; Thiosemicarbazones.