Febrifugine derivative antimalarial activity: quantum mechanical predictors / Descritores da atividade antimalarial de derivados de febrifugina obtidos via mecânica qüântica

Plasmodium falciparum resistant strain development has encouraged the search for new antimalarial drugs. Febrifugine is a natural substance with high activity against P. falciparum presenting strong emetic property and liver toxicity, which prevent it from being used as a clinical drug. The search for analogues that could have a better clinical performance is a current topic. We aim to investigate the theoretical electronic structure by means of febrifugine derivative family semi-empirical molecular orbital calculations, seeking the electronic indexes that could help the design of new efficient derivatives. The theoretical results show there is a clustering in well-defined ranges of several electronic indexes of the most selective molecules. The model proposed for achieving high selectivity was tested with success.

O desenvolvimento de linhagens resistentes de Plasmodium falciparum tem encorajado a busca por novas drogas antimalariais. A febrifugina é uma substância natural com alta atividade contra o P. falciparum que apresenta propriedade emética e toxicidade para o fígado tal que não permitem o seu uso clínico. A busca por análogos que possam ter uma performance clínica melhor é um tema de pesquisa atual. Nosso objetivo é investigar a estrutura eletrônica teórica de uma família de derivados da febrifugina empregando cálculos semi-empíricos de orbitais moleculares, procurando por índices eletrônicos que possam ajudar a modelar novos derivados mais eficientes. Os resultados teóricos mostram que para as moléculas mais seletivas existe um agrupamento dos valores de determinados índices em intervalos bem definidos. O modelo proposto para se obter alta seletividade foi testado com sucesso.

Biological evaluation of novel 6-Arylbenzimidazo [1.2-c] quinazoline derivatives as inhibitors of LPS-induced TNF- alpha secretion

This study describes the effect of novel 6-Arylbenzimidazo [1,2-c] quinazoline derivatives as tumor necrosis factor alpha (TNF-á) production inhibitors. The newly synthesized compounds were tested for their in vitro ability to inhibit the lipolysaccharide (LPS) induced TNF-á secretion in the human promyelocytic cell line HL-60. The compound 6-Phenyl-benzimidazo [1,2-c] quinazoline, coded as Gl, resulted as the most potent inhibitor and with no significant cytotoxic activity. Thus, 6-Arylbenzimidazo [1,2-c] quinazoline derivatives may have a potential as anti-inflammatory agents.

Synthesis and hypoglycemic activity of some new 4[3H]- quinazolinone analogues

The synthesis and biological evaluation of many 3-[4-[[[[cyckohexylamino] carbonyl]amino]sulfonyl]phenyl-4[3H]-quainzolinones [IVa-t] as oral hypoglycemics are described. Derivates [IVf], [IVg], [IVh], [IVj], [IVk], [IVm], [IVq] and [IVr] showed appreciable glucose lowering effects in alloxanized diabetic rats at a dose of 5 mg/kg. They decreased the blood glucose level by 40.7, 36.4, 37.2, 35.4, 43.7, 38.8, 35.3, 42.9 and 45.9 respectively. The hypoglycemic action of the synthesized compounds is comparable to, and in few cases is higher than that exhibited by the well known antidiabetic drug "glyburide" which showed 35.1 percent decrease of the blood glucose level

Synthesis and sterochemical structural elucidation of som partially reduced benzimidazo [2,1-B] quinazoline deriv-atives

This work reported the synthesis of 12-substituted-1, 2, 3, 4, 5, 12- hexahydrobenzimidazo [2,1-b] quinazolines [HHBIQ, 3a-d], 5-phenyl-1, 2, 3, 4, 6, 12 a-hexahydrobenzimidazo [2, 1-b] quinazoline [HHBIQ, 3] and 7-aryl-5, 6, 7, 14-tetrahydrobenzo [h] benzimidazo [2, 1-b] quinazolines [THBBIQ, 3f, g] by the reaction of 2-benzimidazolamine BIA 1 with alpha, beta-unsaturated ketones 2a-g. The structures of these compounds were confirmed with different NMR-experiments [1H and 13C-NMR, HH-COSY, CH-COSY, CHCOLOC and NOE-difference spectra]

1Hand13C NMR assignments of anticonvulsant 4 [3H] -Quinazolinones

A number of 3-[4'-carbamoylphenyl] 2-methyl-4[3H]-quinazolinones were prepared as potential anticonvulsants. Their 1H-and 13CNMR parameters were measured. Assignments of the different proton and carbon signals were made depending on the basis of the chemical shift theory, signal multiplicity, additivity rules and comparison with the data reported for analogous compounds, in addition to CH-COSY and DEPT experiments. By alteration of the substituents on the amide nitrogen, the spin system of the aromatic protons of the 3-[4'-carbamoy1pheny1] moiety could be changed from two doublets of AA' XX' type to a pair doublets of AA'BB' type and finally to a singlet