ABSTRACT
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.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Fatty Acids/chemical synthesis , Fatty Acids/pharmacology , Glioma/pathology , Uridine/analogs & derivatives , Animals , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Chemistry Techniques, Synthetic , Drug Design , Fatty Acids/chemistry , Humans , Male , Rats , Rats, Wistar , Uridine/chemistryABSTRACT
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.
Subject(s)
Amides/chemistry , Fatty Acids/chemistry , Amides/chemical synthesis , Amides/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Resistance, Neoplasm , Drug Screening Assays, Antitumor , Humans , MCF-7 Cells , Ricinoleic Acids/chemistry , Structure-Activity RelationshipABSTRACT
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.
Subject(s)
Antitubercular Agents/chemical synthesis , Antitubercular Agents/pharmacology , Fatty Acids/chemistry , Isoniazid/analogs & derivatives , Isoniazid/pharmacology , Mycobacterium tuberculosis/drug effects , Antitubercular Agents/chemistry , Drug Resistance, Bacterial/drug effects , Isoniazid/chemical synthesis , Microbial Sensitivity Tests , Rifampin/pharmacologyABSTRACT
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.
