Antituberculosis agents and an inhibitor of the para-aminobenzoic acid biosynthetic pathway from Hydnocarpus anthelminthica seeds.

Investigation on the extracts of Hydnocarpus anthelminthica seeds led to the isolation of three new compounds, anthelminthicins A-C (1-3, resp.), and two known ones, namely chaulmoogric acid (4) and ethyl chaulmoograte (5). Their structures were determined mainly by using spectroscopic techniques. The absolute configuration at the cyclopentenyl moiety of compound 2 was rationalized by quantum calculations. Base hydrolysis, followed by optical-rotation comparison, allowed assignment of the configuration of chaulmoogric-acid moiety of compounds 3 and 5. Biological assays revealed that compounds 1-5 significantly inhibit Mycobacterium tuberculosis (MTB) growth with MIC values of 5.54, 16.70, 4.38, 9.82, and 16.80 microM, respectively. Compound 3 was found to inhibit the pathway between chorismate and para-aminobenzoic acid (pAba) with a MIC value of 11.3 microM, representing a new example of pAba inhibitor isolated from a natural source. All compounds were not toxic to Candida albicans SC5314 at a concentration up to 100 microM.

Arylsulfonyl acridinyl derivatives acting on Plasmodium falciparum.

Several arylacridinyl sulfones have been synthesized and their antimalarial action was tested on Plasmodium falciparum. PABA (para-aminobenzoic acid) has no antagonistic effect with these compounds as opposed to the observed effect with dapsone and sulfonamides previously studied. A possible relationship between the ability of cleavage of the S-9C acridinic bond and activity is suggested.

Abyssomicins, inhibitors of the para-aminobenzoic acid pathway produced by the marine Verrucosispora strain AB-18-032.

A screening method was established to detect inhibitors of the biosynthetic pathways of aromatic amino acids and para-aminobenzoic acid, the precursor of folic acid, using an agar plate diffusion assay modified as an antagonism test. By this screening method, a family of three novel polycyclic polyketides named as abyssomicins was isolated from a marine strain of Verrucosispora. The main component abyssomicin C inhibits the pathway between chorismate and para-aminobenzoic acid and is strongly active against gram-positive bacteria, including multi-resistant clinical isolates of Staphylococcus aureus.

Chemical damage in gamma-irradiated human erythrocyte membranes.

In air saturated suspensions of erythrocyte ghost membranes gamma-irradiation causes formation of lipid peroxides, measured as malonaldehyde, and a loss of membrane protein sulphydryl groups. Addition of N-(p-amino-benzoyl)-1-glutamate prevented peroxidation up to doses of 2 x 10(3) Gy, due to scavenging of hydroxyl radicals. Another hydroxyl scavenger sodium formate, also prevented peroxidation at low doses, but lost its protective effect at higher doses probably because of secondary reactions of the resulting superoxide radical anion. Two sulphur containing radioprotectants also were able to reduce the extent of lipid peroxidation. The enzymes catalase and superoxide dismutase were added to the irradiated suspensions in order to determine the contribution from hydrogen peroxide and superoxide to peroxidation. The extents of peroxidation are compared with structural modification of the membrane under the same conditions of irradiation.

[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.