RESUMO
Gallic acid-based indanone derivatives have been synthesised. Some of the indanones showed very good anticancer activity in MTT assay. Compounds 10, 11, 12 and 14 possessed potent anticancer activity against various human cancer cell lines. The most potent indanone (10, IC(50)=2.2 microM), against MCF-7, that is, hormone-dependent breast cancer cell line, showed no toxicity to human erythrocytes even at higher concentrations (100 microg/ml, 258 microM). While, indanones 11, 12 and 14 showed toxicities to erythrocytes at higher concentrations.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Química Farmacêutica/métodos , Ensaios de Seleção de Medicamentos Antitumorais , Ácido Gálico/química , Indanos/síntese química , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Desenho de Fármacos , Eritrócitos/efeitos dos fármacos , Hemólise , Humanos , Indanos/química , Concentração Inibidora 50 , Modelos Químicos , Osmose , Sais de Tetrazólio/farmacologia , Tiazóis/farmacologiaRESUMO
Chalcone derivatives on estradiol framework have been synthesized. Some of the derivatives showed potent anticancer activity against some human cancer cell lines. Compounds 9 and 19 showed potent activity against MCF-7, a hormone dependent breast cancer cell line. Chalcone 7 was further modified to the corresponding indanone derivative (19) using the Nazarov reaction, which showed better activity than the parent compound against the MCF-7 breast cancer cell line. Active anticancer derivatives were also evaluated for osmotic hemolysis using the erythrocyte as a model system. It was observed that chalcone derivatives showing cytotoxicity against cancer cell lines did not affect the fragility of erythrocytes and hence may be considered as non-toxic to normal cells.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Chalcona/análogos & derivados , Estradiol/química , Antineoplásicos/síntese química , Linhagem Celular Tumoral , HumanosRESUMO
Several diverse analogues of Oenostacin, a naturally occurring potent antibacterial phenolic acid derivative, have been synthesized. A small library with more than forty analogues having different aromatic rings and varied side chains has been achieved through solution phase synthesis. Some of these analogues, that is, 22, 23 and 42, possessed potent antibacterial activities against Staphylococcus epidermidis and Staphylococcus aureus having EC(50) ranging from 0.49 to 0.67 microM as compared to Oenostacin (EC(50)=0.12 microM).
Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Hidroxibenzoatos/síntese química , Hidroxibenzoatos/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus epidermidis/efeitos dos fármacos , Antibacterianos/química , Técnicas de Química Combinatória/métodos , Relação Dose-Resposta a Droga , Hidroxibenzoatos/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
Gallic acid, one of the most abundant plant phenolic acids, has been modified to cathepsin D protease inhibitors. The strategy of modification was proposed basing on some previously reported structure and activity relationship (SAR) studies. The synthesized naphthophenone fatty acid amide derivatives have been evaluated for in vitro cathepsin D inhibition activity. Two of them have shown significant inhibition activity with IC(50) values of 0.06 and 0.14 microM, respectively, as compared against pepstatin (0.0023 microM), the most potent inhibitor known so far. The study revealed that such attempts on gallic acid based pharmacophores might result in potent inhibitors of cathepsin D.