Antinociceptive effects of tetrahydrophthalimides and related compounds.

This paper describes the antinociceptive effects of tetrahydrophthalimides and related compounds in mice. Twenty compounds were obtained by the reaction of cis-1,2,3,6-tetrahydrophthalic anhydride with appropriate amines, dehydration, and addition to the imidic double bond. They were analyzed in the writhing test at 10 mg/kg given intraperitoneally. The most active compound 2-benzyl-5-morpholin-4-yl-hexahydroisoindole-1,3-dione (19) was studied on formalin, capsaicin, glutamate and hot plate models. The antinociceptive activity demonstrated by some studied compounds is promising, and some of them were more active than acetylsalicylic acid and paracetamol used as reference drugs in writhing tests in mice. Compound 19 was about 5-fold more potent than the reference drugs, being also effective by oral route and against the inflammatory response in the formalin test. The results suggest that compound 19 could be used as a model to obtain new and more potent antinociceptive agents. It exhibits an interesting antinociceptive profile, and does not interact with opioid systems.

Antinociceptive properties of coumarins, steroid and dihydrostyryl-2-pyrones from Polygala sabulosa (Polygalaceae) in mice.

We have investigated the possible antinociceptive action of the extract, fractions and pure compounds obtained from the whole plant Polygala sabulosa A. W. Bennett (Polygalaceae) in acetic acid-induced visceral pain in mice. Intraperitoneal injection of animals with the hydroalcoholic extract and fractions (CH(2)Cl(2), EtOAc, n-BuOH, aqueous fraction) (1-100 mg kg(-1)) caused a dose-related and significant inhibition of the acetic acid-induced visceral nociceptive response. The CH(2)Cl(2), EtOAc and n-BuOH fractions were more potent than the hydroalcoholic extract and aqueous fraction. The isolated compounds dihydrostyryl-2-pyrones (1, 2, 3), styryl-2-pyrone (7), alpha-spinasterol (9), scopoletin (10) and two esters of the coumarin (scopoletin) obtained semisynthetically, acetylscopoletin (10a) and benzoylscopoletin (10b) (0.001-10 mg kg(-1)), exhibited significant and dose-related antinociceptive effects against acetic acid-induced visceral pain. The results distinguished, for the first time, the extract, fractions and pure compounds obtained from P. sabulosa that produced marked antinociception against the acetic acid-induced visceral nociceptive response, supporting the ethnomedical use of P. sabulosa.

Antimicrobial activity of fractions and compounds from Calophyllumbrasiliense (Clusiaceae/Guttiferae).

Calophyllum brasiliense (Clusiaceae/Guttiferae) is a native Brazilian medicinal plant traditionally used against several diseases, including infectious pathologies. Crude methanolic extracts (CME) and two fractions, denoted non-polar (soluble in chloroform) and polar (nonsoluble in chloroform), were prepared from different parts of the plant (roots, stems, leaves, flowers and fruits) and studied. The following compounds were isolated and tested against pathogenic bacteria and yeasts by determination of the minimal inhibitory concentration (MIC): brasiliensic acid (1), gallic acid (2), epicatechin (3), protocatechuic acid (4), friedelin (5) and 1,5-dihydroxyxanthone (6). The results indicated that all the parts of the plant exhibited antimicrobial activity against Gram-positive bacteria, which are selectively inhibited by components of C. brasiliense. No activity was observed against Gram-negative bacteria and yeasts tested. Regarding the isolated compounds, substance 4 showed antimicrobial activity against all the tested microorganisms, whereas compound 6 exhibited antimicrobial activity only against Gram-positive bacteria. The results from the current study confirm and justify the popular use of this plant to treat infectious processes.