RESUMO
In the work, the in vitro antiproliferative activity of a series of synthetic fatty acid amides were investigated in seven cancer cell lines. The study revealed that most of the compounds showed antiproliferative activity against tested tumor cell lines, mainly on human glioma cells (U251) and human ovarian cancer cells with a multiple drug-resistant phenotype (NCI-ADR/RES). In addition, the fatty methyl benzylamide derived from ricinoleic acid (with the fatty acid obtained from castor oil, a renewable resource) showed a high selectivity with potent growth inhibition and cell death for the glioma cell line-the most aggressive CNS cancer.
Assuntos
Amidas/química , Ácidos Graxos/química , Amidas/síntese química , Amidas/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Células MCF-7 , Ácidos Ricinoleicos/química , Relação Estrutura-AtividadeRESUMO
This work describes the synthesis of a series of fatty acid hydrazide derivatives of isoniazid (INH). The compounds were tested against Mycobacterium tuberculosis H37Rv (ATCC 27294) as well as INH-resistant (ATCC 35822 and 1896 HF) and rifampicin-resistant (ATCC 35338) M. tuberculosis strains. The fatty acid derivatives of INH showed high antimycobacterial potency against the studied strains, which is desirable for a pharmaceutical compound, suggesting that the increased lipophilicity of isoniazid plays an important role in its antimycobacterial activity.
Assuntos
Antituberculosos/síntese química , Antituberculosos/farmacologia , Ácidos Graxos/química , Isoniazida/análogos & derivados , Isoniazida/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Antituberculosos/química , Farmacorresistência Bacteriana/efeitos dos fármacos , Isoniazida/síntese química , Testes de Sensibilidade Microbiana , Rifampina/farmacologiaRESUMO
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.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Ácidos Graxos/síntese química , Ácidos Graxos/farmacologia , Glioma/patologia , Uridina/análogos & derivados , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Técnicas de Química Sintética , Desenho de Fármacos , Ácidos Graxos/química , Humanos , Masculino , Ratos , Ratos Wistar , Uridina/químicaRESUMO
An efficient and green synthesis of thiocarbamoyl-3,5-diaryl-4,5-dihydro-1H-pyrazoles via the condensation of chalcones with thiosemicarbazide in ethanol and KOH under ultrasound irradiation is reported. The products were isolated in good yields after short reaction times.