1175656-95-7Relevant academic research and scientific papers
4-Fluorobenzaldehyde limonene-based thiosemicarbazone induces apoptosis in PC-3 human prostate cancer cells
dos Santos Rodrigues, Bruna,de ávila, Renato Ivan,Benfica, Polyana Lopes,Bringel, Ludmila Pires,de Oliveira, Cecília Maria Alves,Vandresen, Fábio,da Silva, Cleuza Concei??o,Valadares, Marize Campos
, p. 141 - 149 (2018)
Aims: This study evaluated parameters of toxicity and antiproliferative effects of (+)-N(1)-4-fluorobenzaldehyde-N(4)-{1-methyl-1-[(1R)-4-methylcyclohexene-3-il]-ethyl}-thiossemicarbazone (4-FTSC) in PC-3 adenocarcinoma prostate cells. Main methods: Cytotoxicity of 4-FTSC in PC-3 cells was evaluated using MTT assay. Morphology examination of PC-3 cells treated with 4-FTSC was also performed as well as the cell death mechanisms induced were investigated using flow cytometry. Parameters of toxicity of 4-FTSC was conducted by the investigation of its potential myelotoxicity and lymphotoxicity, hemolytic activity and acute oral toxicity profile. Key findings: 4-FTSC showed promising cytotoxic effects against PC-3 cells (IC50 = 18.46 μM). It also triggered apoptotic morphological changes, phosphatidylserine externalization and a significant increase of DNA fragmentation in PC-3 cells. Moreover, 4-FTSC did not show changes in the PC-3 cell cycle with levels of p21, p27, NF?B and cyclin D1 similar to those found in both control and treated cells. 4-FTSC also promoted an increase of p53 levels associated with mitochondrial impairment through loss of ?Ψm and ROS overproduction. 4-FTSC-induced cell death mechanism in PC-3 cells involved activation of caspase-3/-7 through apoptosis intrinsic pathway via caspase-9. Regarding toxicological profile, 4-FTSC showed in vitro lymphotoxicity, although with low cytotoxicity for bone marrow progenitors and no hemolytic potential. Moreover, it was classified as GHS category 5 (LD50 > 2000–5000 mg/Kg), suggesting it has low acute oral systemic toxicity. Significance: 4-FTSC seems to be a promising candidate to be used as a clinical tool in prostate cancer treatment. Further studies are required to better clarify its toxicopharmacological effects found in this compound.
Novel R-(+)-limonene-based thiosemicarbazones and their antitumor activity against human tumor cell lines
Vandresen, Fábio,Falzirolli, Hugo,Almeida Batista, Sabrina A.,Da Silva-Giardini, Ana Paula B.,De Oliveira, Diogo N.,Catharino, Rodrigo R.,Ruiz, Ana Lúcia T.G.,De Carvalho, Jo?o E.,Foglio, Mary Ann,Da Silva, Cleuza Concei??o
, p. 110 - 116 (2014)
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.
Synthesis and comparison of antileishmanial and cytotoxic activities of S-(?)-limonene benzaldehyde thiosemicarbazones with their R-(+)-analogues
Almeida Batista, Sabrina A.,Vandresen, Fábio,Falzirolli, Hugo,Britta, Elizandra,de Oliveira, Diogo N.,Catharino, Rodrigo R.,Gon?alves, Mateus A.,Ramalho, Teodorico C.,La Porta, Felipe A.,Nakamura, Celso V.,da Silva, Cleuza C.
, p. 252 - 262 (2019)
In this study, we explore a series of novel potential antiprotozoal S-(?)-limonene-based benzaldehyde thiosemicarbazones were synthesised and their activity effective against the extracellular promastigote form of Leishmania amazonensis examined. Likewise, in parallel, a series of R-(+)-limonene-based thiosemicarbazones previously synthesised by our research group and thiosemicarbazones lacking the monoterpenic moiety, were also biologically evaluated. Here, we report the combination of theoretical and experimental approaches, as well as statistical analysis, to investigate the effect of the monoterpenic group and its stereochemistry in the biological activity of benzaldehyde thiosemicarbazone derivatives, for the identification of their structure-activity relationship. The terpenic thiosemicarbazones displayed the highest activities, confirming that the monoterpenic moiety is essential for activity. Notably, among the compounds tested, the S-(?)-enantiomer of the 4-nitro-derivative (8d) presented considerably lower cytotoxicity than its R-(+)-analogue, emphasizing the importance of the stereochemistry. The most active derivative (8d) exhibited a potent antiprotozoal activity (IC50 2.4 μM) and high selectivity (SI > 1147). Also, theoretical calculations were carried out at the density functional theory (DFT) level to show that the Gibbs free energy and LUMO orbitals present an excellent correlation with the experimental IC50 values. Finally, the combination of all these results may in principle be extremely advantageous to a deeper chemical understanding, as well as, allows a rational alternative for the future development of new drugs that act against leishmaniasis.
