Indole and β-Carboline Alkaloids from Geissospermum sericeum

Abstract

The indole alkaloid geissoschizoline (1) and two new derivatives, geissoschizoline N(4)-oxide (2) and 1,2-dehydrogeissoschizoline (3), were obtained from the bark of Geissospermum sericeum together with the beta-carboline alkaloid flavopereirine (4). The in vitro antiplasmodial activity of these compounds was evaluated in chloroquine-resistant (K1) and chloroquine-sensitive (T9-96) Plasmodium falciparum. Their cytotoxicity was determined in a human (KB) cell line.

Plant-derived antimalarial agents: new leads and efficient phythomedicines. Part I. Alkaloids

“…In addition, even the alkaloidal fractions obtained by sequential extractions with Et 2 O, CHCl 3 and EtOAc were less active (with IC 50 values of 10.15, 2.21 and 2.47μg/ml, respectively). This result suggests that compounds other than alkaloids might be responsible for the antiplasmodial activity of G. sericeum (Steele et al 2002). The antiplasmodial activity displayed in vitro by the crude extract of G. sericeum and some of its alkaloidal constituents seem to confirm earlier reports describing the traditional use of this plant for the treatment of malaria by populations from the Amazonia region (Milliken andAlbert 1997, Brandão et al 1992).…”

“…However, although the most extensively used techniques are the traditional microscopic and radioisotopic ([ 3 H]-hypoxanthine) assays, the LDH and haem-targeted assays are being explored (Wright et al 2001, Steele et al 2002, Ajaiyeoba et al 2005.…”

“…From alkaloidal fractions, four alkaloids were isolated: geissoschizoline and flavopereirine, which were previously isolated from G. vellosii and G. laeve, and geissoschizoline N 4 -oxide and 1,2-dehydrogeissoschizoline, which are novel natural indolomonoterpenoid derivatives (Steele et al 2002;Chart 7). Flavopereirine, a β-carboline alkaloid, was the most active of the four compounds that were assayed against K1 (CQR) and T9-96 (CQS) strains of P. falciparum (IC 50 = 11.53 and 1.83μM, respectively), but it also showed moderate cytotoxicity against KB cells (IC 50 = 10.7μM), with essentially no selectivity against the K1 strain.…”

The plant extract ofPao pereirapotentiates carboplatin effects against ovarian cancer

“…It contains the alkaloid flavopereirine (also called PB-100), as well as many other kinds of indole and b-carboline alkaloids (Puiseux et al, 1959;Reina et al, 2012;Steele et al, 2002). According to anecdotal reports and some inconclusive evidence, flavopereirine or Pao may be of benefit for the treatment of malaria, cancer (including prostate cancer, glioblastoma and leukemia), HIV/AIDS, herpes simplex and hepatitis C (Beljanski & Beljanski, 1982;Beljanski et al, 1993;Bemis et al, 2009;Reina et al, 2012;Steele et al, 2002). However, Pao is commonly administered together with other herbal remedies, including ginkgo (Ginkgo biloba) and the indole alkaloid alstonine, which may have antipsychotic properties.…”

“…As early as in 1959, three alkaloids were isolated from Geissospermum leave (Vellozo) Baillon: geissoschizoline, apogeissoschizine and geissospermine, but without testing their antitumor activities (Puiseux et al, 1959). Later, Steele et al (2002) reported isolation of the three indole alkaloids and a b-carboline alkaloid flavopereirine from the bark of Geissospermum sericeum and their antiplasmodial activities. Reina et al (2012) reported seven indole alkaloids from the leaves and three from the bark of Geissospermum reticulatum and the antiparasitic activities of both the extract and each alkaloid.…”