Prenylated flavanone derivatives isolated from Erythrina addisoniae are potent inducers of apoptotic cell death

NoExtracts of Erythrina addisoniae are frequently used in the traditional medicine of Western Africa, but insufficient information about active compounds is available. From the stem bark of E. addisoniae, three (1, 2, 4) and three known (3, 5, 6) flavanones were isolated: addisoniaflavanones I and II, containing either a 2″,3″-epoxyprenyl moiety (1) or a 2″,3″-dihydroxyprenyl moiety (2) were shown to be highly toxic (MTT assay: EC50 values of 5.25 ± 0.7 and 8.5 ± 1.3 μM, respectively) to H4IIE hepatoma cells. The cytotoxic potential of the other isolated flavanones was weaker (range of EC50 values between 15 and >100 μM). Toxic effects of addisoniaflavanone I and II were detectable after 3 h (MTT assay). Both compounds induced an apoptotic cell death (caspase-3/7 activation, nuclear fragmentation) in the hepatoma cells and, at high concentrations, also necrosis (membrane disruption: ethidium bromide staining). Formation of DNA strand breaks was not detectable after incubation with these compounds (comet assay). In conclusion, the prenylated flavanones addisoniaflavanones I and II may be of interest for pharmacological purposes due to their high cytotoxic and pro-apoptotic potential against hepatoma cells

Prenylated flavonoid derivatives from the bark of Erythrina addisoniae.

noTwo new prenylated flavanones, 2S-3¿-(2-hydroxy-3-methylbut-3-enyl)licoflavone-4¿-methyl ether (3) and 2S-3¿-(2- hydroxy-3-methylbut-3-enyl)abyssinone II (4), and four known flavanones (1, 2, 5, 6) were isolated from the stem bark of Erythrina addisoniae. The structures were elucidated on the basis of their spectroscopic and physicochemical data. None of the compounds showed antioxidative properties. 4¿-Methylabyssinone V (1) and abyssinoflavanone VII (6) showed moderate cytotoxic activity (IC50 ) 5 and 3.5 ¿mol/L, respectively), but apoptosis (caspase-3/7-activation, nuclear fragmentation) was selectively induced by abyssinoflavanone VII (6)

Antiplasmodial Activities Of Sesquiterpene Lactones From Eupatorium Semialatum

Eupatorium semialatum is a member of the Asteraceae, which occurs in Guatemala. Previously, we reported the occurrence of sesquiterpene lactones of the eudesmanolide type as main constituents in the leaves. This paper deals with the isolation and identification of the first guaianolide found in E. semialatum. Since this plant is used against malaria and other diseases in the Guatemalan folk medicine, the main sesquiterpene lactones were tested for their activities against Plasmodium falciparum in vitro</jats:p

Isolation and in vitro antiplasmodial activities of alkaloids from Teclea trichocarpa: in vivo antimalarial activity and X-ray crystal structure of normelicopicine.

Seven alkaloids have been isolated from Teclea trichocarpa including four, normelicopicine (1), arborinine (2), skimmianine (6), and dictamnine (7), that are reported for the first time in addition to the previously reported alkaloids melicopicine (3), tecleanthine (4), and 6-methoxytecleanthine (5). The structure of 1 was confirmed by single-crystal X-ray crystallography. Two alkaloids, 1 and 2, displayed limited in vitro activities against Plasmodium falciparum strains HB3 and K1, but there appeared to be little cross-resistance with chloroquine. Alkaloid 1 was found to have some activity against P. berghei in mice (32% suppression of parasitaemia at a dose of 25 mg x kg(-1) x day(-1)), but unlike chloroquine it did not inhibit beta-haematin formation in a cell-free system; 1 was found to have low in vitro cytotoxicity to KB cells (IC50 > 328 microM)

Synthesis and evaluation of cryptolepine analogues for their potential as new antimalarial agents

NoThe indoloquinoline alkaloid cryptolepine 1 has potent in vitro antiplasmodial activity, but it is also a DNA intercalator with cytotoxic properties. We have shown that the antiplasmodial mechanism of 1 is likely to be due, at least in part, to a chloroquine-like action that does not depend on intercalation into DNA. A number of substituted analogues of 1 have been prepared that have potent activities against both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum and also have in common with chloroquine the inhibition of ß-hematin formation in a cell-free system. Several compounds also displayed activity against Plasmodium berghei in mice, the most potent being 2,7-dibromocryptolepine 8, which suppressed parasitemia by 89% as compared to untreated infected controls at a dose of 12.5 mg kg-1 day-1 ip. No correlation was observed between in vitro cytotoxicity and the effect of compounds on the melting point of DNA (¿Tm value) or toxicity in the mouse¿malaria model

Isolation and in Vitro Antiplasmodial Activities of Alkaloids from <i>Teclea </i><i>t</i><i>richocarpa</i>: In Vivo Antimalarial Activity and X-ray Crystal Structure of Normelicopicine

Seven alkaloids have been isolated from Teclea trichocarpa including four, normelicopicine (1), arborinine (2), skimmianine (6), and dictamnine (7), that are reported for the first time in addition to the previously reported alkaloids melicopicine (3), tecleanthine (4), and 6-methoxytecleanthine (5). The structure of 1 was confirmed by single-crystal X-ray crystallography. Two alkaloids, 1 and 2, displayed limited in vitro activities against Plasmodium falciparum strains HB3 and K1, but there appeared to be little cross-resistance with chloroquine. Alkaloid 1 was found to have some activity against P. berghei in mice (32% suppression of parasitaemia at a dose of 25 mg kg-1 day-1), but unlike chloroquine it did not inhibit β-haematin formation in a cell-free system; 1 was found to have low in vitro cytotoxicity to KB cells (IC50 > 328 μM)