Antimalarial activity of oxidized starch and cellulose imine derivatives.

With the purpose of screening potential antimalarial agents, oxidized starch imine derivatives of sulfonamides or pyrimidine - derivatives of sulfisoxazole (ML8), sulfameter (ML11) and trimethoprim (ML13) - and oxidized cellulose imine derivatives of dapsone (ML14), sulfadiazine (ML17), sulfamethoxazole (ML18), sulfisoxazole (ML19), sulfamethoxypyridazine (ML20) and sulfameter (ML22) were submitted to in vivo biological assays with mice infected with Plasmodium berghei. Only ML11 was 100% curative in test conditions; ML 17 showed the same effect as its prototype. The drug content in both prodrugs is lower in the applied dose than that used in the original drugs. It can be suggested that the latentiation enhanced the effectiveness of the prototypes.

Quantitative structure-activity relationships for 1,4-dihydropyridine calcium channel antagonists (nifedipine analogues): a quantum chemical/classical approach.

A quantum chemical (AM1) combined with a classical study of structure-activity relationships for 1,4-dihydropyridines (nifedipine analogues) was performed. The biological data were taken from the literature. The quantum chemical parameters tested were energies of HOMO and LUMO, dipole moment (total and partial), hardness, Mulliken electronegativity, frontier orbital indices, and others. Also tested were classical parameters like Hansch hydrophobic constant, tau; Hammett electronic constant for the meta position, sigma m; and the Verloop sterimol parameters, B1 and L. The van der Waals volume was also tested. The pharmacological activities of the para monoderivatives are negatively correlated with the molecular volume, i.e. a steric factor. The meta position of the phenyl ring is affected by steric and electronic parameters, whereas the ortho position seems to be affected by hydrophobic and electronic parameters.

Analise espectrometrica do benznidazol. / Spectrometric analysis of benznidazole

Com o intuito de suprir lacuna na bibliografia quimico-analitico dedicada ao benznidazol, foram executados e interpretados os espectrogramas de massa, ressonancia magnetica protonica, infravermelho e ultravioleta do novo composto.Nas quatro variedades de analise instrumental procurou-se comparar as propriedades espectrometricas e espectrofotometricas da molecula com as de outros nitroimidazois descritos na literatura

Doseamento da cimetidina pelo metodo de Kjeldahl. / Determination of cimetidine by Kjeldahl's method

O nitrogenio contido na molecula da cimetidina foi determinado quantitativamente pelo metodo de Kjeldahl usando quatro condicoes diferentes. A variante que deu melhor resultado consiste em hidrolisar previamente o grupo ciano do farmaco com acido antes de submeter a cimetidina a acao oxidante do acido sulfurico concentrado

Latenciacao de quimioterapicos: preparacao de polimeros sacaridicos de agentes esquistossomicidas e antimalaricos / Latentiation of chemotherapeutical agents: preparation of saccharide polymers of schistosomicidal and antimalaria agents

Visando a obtencao de pro-farmacos de acao prolongada e de menor toxicidade que os prototipos, foram preparados polimeros sacaridicos de agentes esquistossomicidas (anfotalida e pararrosanilina) e de antimalaricos (dapsona, pirimetamina, trimetoprina e sulfadimetoxina). Os produtos foram obtidos mediante reacao do cloroformiato de amido a temperatura ambiente e a 60 graus C com os agentes biologicamente ativos. Dos produtos obtidos, apenas o polimero sacaridico da dapsona preparado a temperatura de 60 graus C (CFA-lt) e o polimero sacaridico da pirimetamina preparado a temperatura ambiente (CFA-3) mostraram-se ativos - o primeiro, parcialmente - quando ensaiados, respectivamente, em malária e esquistossomíase experimentais

Latenciaçäo de agentes esquistossomicidas e antimalarios / Latentiation of schistosomicidal and antimalarial agents

Atraves do uso da latenciacao, foram preparados pro-farmacos de agentes antimalaricos (dapsona, trimetoprina, cicloguanila, pirimetamina, sulfamonometoxina, sulfadiazina, sulfamerazina e sulfatiazol) e agentes esquistossomicidas (oxamniquina anfotalida e pararrosanilina). Os produtos foram obtidos mediante reacao dos agentes ativos com o acido metacrilico, resultando os monomeros, e com o acido metacrilico, resultando os monomeros, e com o acido polimetacrilico, originando os polimeros. Submetidos a ensaios biológicos, a maioria mostrou atividade

Antimalarial activity of saccharidic polymers of dapsone and sulfadimethoxine.

With the purpose of obtaining pro-drugs of dapsone and sulfadimethoxine, those chemotherapeutic agents were attached through covalent bonding to starch polymeric dialdehyde (Sumstar-190). The antimalarial activity of the two resulting compounds - the dapsone saccharidic polymer (PS6) and the sulfadimethoxine saccharidic polymer (PS7) - in mice experimentally inoculated with Plasmodium berghei was significantly increased with this molecular modification. Mice infected with malaria and kept without treatment together with others which received different doses of PS6 and PS7 were also partially or totally cured, possibly due to the ingestion of excrements containing the parent chemotherapeutic agents.

[Conformations and interatomic distances in polymorphs of sulfanilamide]. / Conformações e distâncias interatômicas em polimorfos da sulfanilamida.

By CNDO (Complete Neglect of Differential Overlap) molecular orbital method, interatomic distances and XYZ cartesian corrdinates were calculated in five polymorphs (monohydrated, alpha, two beta, and gamma) of sulfanilamide. Interatomic distances thus obtained are very close to those originally presented by Bells & Roblin and support the mechanism of action postulated long algo for sulfa drugs as being competitive antagonism with p-aminobenzoic acid.

[Latentiation of therapeutic drugs. VI. Preparation of l-amino-4-naphtylazoic ambonates of schistosomicides]. / Latenciação de quimioterápicos. VI. Preparaçáo de embonatos de 1-amino-4-naftilazóicos esquistossomicidas

With the purpose of obtaining latent forms, with prolonged action and less toxic, of four schistosomicidal 1-amino-4-naphthylazoderivatives synthesized early, embonates of these compounds were prepared by reacting disodium and tetrasodium embonates with hydrochlorides of the four naphthylazoderivatives. The eight embonates thus obtained were sent for biological assays.

[Synthesis and biological trial of 1-methylene-4-naphthylazo polymer derivates]. / Síntese e ensaio biológico de 1-metilenamino-4-naftilazoderivados poliméricos

With the purpose of preparing latent forms of six naphthylazoderivatives (five of them are schistosomicidal agents), polymers of these chemotherapeutic agents were synthesized in a two-step reaction. First, polymeric 1-methyleneaminonaphthalene (II) was synthesized by condensing 1-naphthylamine with formaldehyde. Subsequently, coupling of II with five sulfonamides (of which four are moieties of schistosomicidal agents) and 5-aminouracil (which is a part of another schistosomidical agent) yielded polymeric 1-methyleneamino-4-naphthylazoderivaties (IIIa-f). In bioligical tests in mice experimentally infected by Schistosoma mansoni, the six new polymers were found inactive.