RESUMO
A series of 4-piperidone based curcuminoids were synthesized and anticancer potential of these compounds was evaluated against human myeloid leukemia (KBM5) and colon cancer (HCT116) cell lines. Their anti-inflammatory potential was determined through the down-regulation of tumor necrosis factor (TNF)-α-induced nuclear factor (NF)-κB. All compounds, except one, were found to exhibit better cytotoxicity than curcumin at 5 µM. Furthermore, many compounds have shown good potential to inhibit the TNF-α-induced NF-κB activation. Docking study of the compounds with NF-κB revealed that the binding affinity of the compounds ranged from â9.0 to â6.5 kcal/mol with 0-8 H-bonds. It was also observed that amido-ether based mono-carbonyl compounds bound around the same region of NF-κB where polynucleotides are known to bind to exhibit their activity.
Assuntos
Curcumina/síntese química , Piperidonas/química , Curcumina/química , Curcumina/farmacologia , Simulação de Acoplamento Molecular , Análise Espectral/métodosRESUMO
In a search of new compounds active against cancer, synthesis of a series of C-5 curcumin analogues was carried out. The new compounds demonstrated good cytotoxicity against chronic myeloid leukemia (KBM5) and colon cancer (HCT116) cell lines. Further, these compounds were found to have better potential to inhibit TNF-α-induced NF-κB activation in comparison to curcumin, which show their potential to act as anti-inflammatory agents. Some compounds were found to show higher cytotoxicity against cancer cell lines in comparison to curcumin used as standard.
Assuntos
Antineoplásicos/síntese química , Curcumina/análogos & derivados , Curcumina/síntese química , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Anti-Inflamatórios/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Curcumina/química , Curcumina/farmacologia , Regulação para Baixo/efeitos dos fármacos , Ensaio de Desvio de Mobilidade Eletroforética , HumanosRESUMO
Trichomoniasis is the most prevalent, curable sexually transmitted disease (STD), which increases risk of viral STDs and HIV. However, drug resistance has been developed by some strains of Trichomonas vaginalis against Metronidazole (MTZ), the FDA approved drug against trichomoniasis. In the present study twenty two chalcone hybrids of metronidazole have been synthesized in a quest to get new molecules with higher potential against metronidazole-resistant T. vaginalis. All new hybrid molecules were found active against T. vaginalis with varying levels of activity against MTZ-susceptible and resistant strains. Eight compounds (4a, 4c, 4d, 4e, 4f, 4h, 4q and 4s) were found as active as the standard drug with an MIC of 1.56 µg/ml against MTZ-susceptible strain. However, compounds 4e, 4h and 4m were 4-times more active than MTZ against drug-resistant T. vaginalis, amongst which 4e and 4h were most promising against both susceptible and resistant strains.