RESUMO
A series of new 4ß-carbamoyl epipodophyllotoxin analogues have been synthesized and evaluated for their anticancer activity against eleven cancer cell lines including Zr-75-1, MCF7, KB, Gurav, DWD, Colo 205, A-549, Hop62, PC3, SiHa and A-2780. Most of the compounds exhibited better growth-inhibition activities against tested cell lines than that of etoposide. Further, compounds 6g and 6i are also evaluated for their DNA topoisomerase-II (topo-II) inhibition activity and they exhibited significant inhibition of topo-II catalytic activity comparable to etoposide.
Assuntos
Antineoplásicos/síntese química , Podofilotoxina/análogos & derivados , Antineoplásicos/uso terapêutico , Antineoplásicos/toxicidade , Linhagem Celular Tumoral , DNA Topoisomerases Tipo II/química , DNA Topoisomerases Tipo II/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Etoposídeo/toxicidade , Humanos , Neoplasias/tratamento farmacológico , Podofilotoxina/uso terapêutico , Podofilotoxina/toxicidade , Inibidores da Topoisomerase II/química , Inibidores da Topoisomerase II/uso terapêutico , Inibidores da Topoisomerase II/toxicidadeRESUMO
An efficient one-pot iodination methodology for the synthesis of benzothiazolo-4ß-anilino-podophyllotoxin (5a-h) and benzothiazolo-4ß-anilino-4-O-demethylepipodophyllotoxin (6a-h) congeners has been successfully developed by using zirconium tetrachloride/sodium iodide. Interestingly, this protocol demonstrates enhancement of stereoselectivity apart from the improvement in the yields in comparison to previous methods reported for such related podophyllotoxin derivatives. These compounds have been designed and synthesized using association strategy by coupling of 4ß-podophyllotoxin and 4ß-demethylepipodophyllotoxin with a variety of substituted aminoaryl benzothiazoles. Some of the representative compounds have been evaluated for their cytotoxicity against selected human cancer cell lines and DNA topoisomerase-II inhibition activity.
Assuntos
Antineoplásicos/síntese química , Benzotiazóis/química , DNA Topoisomerases Tipo II/química , Podofilotoxina/química , Inibidores da Topoisomerase II/síntese química , Antineoplásicos/uso terapêutico , Antineoplásicos/toxicidade , Linhagem Celular Tumoral , Cloretos/química , DNA Topoisomerases Tipo II/metabolismo , Halogenação , Humanos , Neoplasias/tratamento farmacológico , Podofilotoxina/uso terapêutico , Podofilotoxina/toxicidade , Inibidores da Topoisomerase II/uso terapêutico , Inibidores da Topoisomerase II/toxicidade , Zircônio/químicaRESUMO
A new class of 4ß-N-polyaromatic substituted podophyllotoxin congeners have been synthesized and evaluated for their DNA topoisomerase-II (topo-II) inhibition as well as anticancer potential in some human cancer cell lines. The ease of synthesis and interesting biological activities make the present series of polyaromatic-podophyllotoxin congeners as a promising new structure for the development of new anticancer agents based on podophyllotoxin scaffold.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , DNA Topoisomerases Tipo II/efeitos dos fármacos , Podofilotoxina/síntese química , Inibidores da Topoisomerase II/síntese química , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Podofilotoxina/farmacologia , Inibidores da Topoisomerase II/farmacologiaRESUMO
An efficient and facile nitration of phenols using nitric acid/zinc chloride under ultrasonic condition has exhibited significant chemo as well as regioselectivity. This study has been extended to other aromatic compounds like naphthalene and anthracene.
