RESUMO
We describe herein asymmetric synthesis of a novel anticancer beta-lactam following Staudinger reaction with chiral carbohydrate as the ketene component with an achiral imine. The in vitro cytotoxicity studies of these beta-lactams are also reported here.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Carboidratos/química , Etilenos/química , Cetonas/química , beta-Lactamas/síntese química , beta-Lactamas/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Estereoisomerismo , beta-Lactamas/químicaRESUMO
Stereocontrolled synthesis of novel beta-lactams using polyaromatic imines following the Staudinger reaction has been accomplished. The effects of domestic microwave irradiation on this type of reaction have been investigated. Formation of trans-beta-lactams has been explained through isomerization of the enolates formed during the reaction of acid chloride (equivalent) with imines in the presence of triethylamine. A donor-acceptor complex pathway is believed to be involved in the formation of cis-beta-lactams. The effect of a peri hydrogen has been found to be significant in controlling the stereochemistry of the resulting beta-lactams. SAR has identified beta-lactams with anticancer activity. The presence of an acetoxy group has proven obligatory for their anticancer activity.
Assuntos
Antineoplásicos/síntese química , beta-Lactamas/síntese química , Antineoplásicos/química , Iminas/química , Espectroscopia de Ressonância Magnética , Micro-Ondas , Espectrofotometria Infravermelho , Estereoisomerismo , beta-Lactamas/químicaRESUMO
Synthesis of the trans 1-N-chrysenyl and 1-N-phenanthrenyl 3-acetoxy-4-phenyl-2-azetidinones has been achieved. Microwave-assisted reaction has proved useful in the synthesis of these compounds. Cell growth inhibition study has indicated selective anticancer activity against two leukemia and colon carcinoma cell lines. A mechanistic correlation of their anticancer activity has been described. Striking G2 blockade that is clearly distinct in cell cycle analysis and demonstrated only in sensitive cell lines has been observed. They do not induce apoptosis in sensitive or resistant lines. They also do not inhibit topoisomerases. Ames test has shown they are nonmutagenic.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , beta-Lactamas/síntese química , beta-Lactamas/farmacologia , Antineoplásicos/química , Apoptose , Bioensaio , Linhagem Celular Tumoral , Humanos , Estrutura Molecular , Testes de Mutagenicidade , Inibidores da Topoisomerase I , Inibidores da Topoisomerase II , beta-Lactamas/químicaRESUMO
Simple synthesis of substituted pyrroles using iodine-catalyzed and montmorillonite KSF-clay-induced modified Paal-Knorr methods has been accomplished with excellent yields. N-Substituted carbazole has also been prepared by following this method. If one of the reactants is a liquid, the reaction proceeds exceedingly well without a solvent. This method gives pyrroles with less nucleophilic multicyclic aromatic amines at room temperature.
Assuntos
Pirróis/síntese química , Pirróis/químicaRESUMO
We present herein stereoselective synthesis of novel beta-lactams using polyaromatic imines following the Staudinger reaction. Consistent mechanisms for these results have been advanced. As a measure of cytotoxicity, some of these compounds have been assayed against nine human cancer cell lines. Structure-activity study has revealed that 1-N-chrysenyl and 1-N-phenanthrenyl 3-acetoxy-4-aryl-2-azetidinones have potent anticancer activity. The presence of the acetoxy group at C(3) of the beta-lactams has proven to be obligatory for their anticancer activity.
