RESUMO
Novel bis-heterocyclic bisphosphonates/phosphonamidates were synthesized utilizing the Pudovick reaction. The employment of Nb(2)O(5) as catalyst was found to increase the yields and purity of the bisbenzoxazaphosphine derivatives (13a-h). Their anticancer activity studies in vitro, on three human tumor cell lines NCI-H460 (lung large cell), MCF-7 (breast adenocarcinoma), and SF-268 (central nervous system glioblastoma), showed that bis-[3-(3-chloro-4-fluorophenyl)-2-oxo-3,4-dihydro-2H-2lambda(5)-benzo[e][1,3,2]oxazaphosphinin-2-yl]arylmethanes (13a-h) and [(4-chlorophenyl)-(hydroxyamidophosphinoyl)-methyl]phosphonic acid (14) exhibited significant anticancer activity.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Compostos Heterocíclicos/síntese química , Compostos Heterocíclicos/farmacologia , Hidrocarbonetos Clorados/síntese química , Hidrocarbonetos Clorados/farmacologia , Neoplasias/tratamento farmacológico , Organofosfonatos/síntese química , Organofosfonatos/farmacologia , Clorobenzenos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Neoplasias/patologia , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
Synthesis of some new substituted [3-(3-chloro-4-fluorophenyl)-2-oxo-3,4-dihydro-2H-2lambda(5)-benzo[e][1,3,2]oxazaphosphinin-2-yl]-(aryl/alkyl)methanols (7a-k) based on the Pudovick reaction was accomplished in the presence of niobium pentoxide (Nb(2)O(5)) without using an external chiral ligand. Nb(2)O(5) appears to form the metal complex intermediate catalyst system (6) by reacting with 3-(3-chloro-4-fluoro-phenyl)-3,4-dihydrobenzo[e][1,3,2]oxazaphosphinine-2-oxide (4), which not only directs the Pudovick addition reactions of aldehyde but also increases the yields and purity of the products. These compounds exhibited a lethal effect on whip smut of sugarcane and were degraded in the environment in the presence of bacteria and fungi to nontoxic phosphate residues that act as possible plant nutrients. Thus, a new class of benzooxazaphosphininyl methanol derivatives that act in synergy both as antipathogens and as plant nutrients in the environment have been discovered.
Assuntos
Alcanos/síntese química , Alcanos/farmacologia , Fungicidas Industriais/síntese química , Fungicidas Industriais/farmacologia , Compostos Heterocíclicos com 2 Anéis/síntese química , Compostos Heterocíclicos com 2 Anéis/farmacologia , Saccharum/microbiologia , Ustilago/efeitos dos fármacos , Nióbio/química , Óxidos/químicaRESUMO
Several new substituted oxazaphosphorinyl urea derivatives of the type RR'P(O)NHC(O)NHR'' were synthesized from alpha-(3-chloro-4-fluoroanilino)-o-cresol by reaction with chlorides of aryl/alkyl/cyclohexyl carbamidophosphoric acids in the presence of triethylamine at 0-50 degrees C. Their significant insecticidal and antimicrobial activity and promotion of Rhizobium bacteria growth in the soil without effect on the host tissue suggests their possible commercial application as ecofriendly pesticides and antimicrobial agents.
Assuntos
Ureia/análogos & derivados , Ureia/síntese química , Alternaria/efeitos dos fármacos , Animais , Antibacterianos/síntese química , Antibacterianos/farmacologia , Antifúngicos/síntese química , Antifúngicos/farmacologia , Aspergillus niger/efeitos dos fármacos , Bacillus subtilis/efeitos dos fármacos , Bombyx/efeitos dos fármacos , Besouros/efeitos dos fármacos , Inseticidas/síntese química , Inseticidas/farmacologia , Estrutura Molecular , Óvulo/efeitos dos fármacos , Rhizobium/efeitos dos fármacos , Ureia/farmacologiaRESUMO
Twenty-one types of novel ellipticine derivatives and pyridocarbazoles (5-methoxycarbonyl-11-methyl-6H-pyrido[4,3-b]carbazoles) with a nitrosourea moiety, linked by an oxydiethylene unit at the 2 position, were synthesized, and their cytotoxicity against HeLa S-3 cells was evaluated. Some of these new compounds exhibited potent antitumor activity by comparison with that of ellipticine.