Activity of Isoflavans ofDalea aurea(Fabaceae) against the Opportunistic AmebaNaegleria fowleri

Abstract

One new and one known isoflavan, 3 S(+)-7-methoxymanuifolin K (1) and manuifolin K (2), respectively, were isolated from methanolic extracts of Dalea aurea (Fabaceae). Isoflavans 1 and 2 exhibited significant in vitro activity against the ameba Naegleria fowleri, an organism responsible for an infrequent but rapidly fatal form of primary amebic meningoencephalitis (PAM). At concentrations of 30 microM, both 1 and 2 caused growth inhibition of N. fowleri at a level comparable to amphotericin B (at 0.1 microM), the currently preferred treatment for this disease. Over a seven-day growth period, 1 and 2 (30 microM) exhibited superior growth inhibition of N. fowleri than amphotericin B after day 4. Isoflavan 2 was evaluated in a mouse model of PAM at a dose of 25 mg/kg/day for five days. While amphotericin B (2.5 mg/kg/day) offered 12.5 % protection of the mice, compound 2 did not protect the mice from PAM infection compared to controls.

Naegleria fowleri after 50 years: is it a neglected pathogen?

“…dexamethasone) and non-pharmacological procedures like CSF drainage, hyperosmolar therapy, moderate hyperventilation and hypothermia (Cope et al, 2016). Some of the studies aimed at finding novel therapeutic drugs focussed on compounds such as acrolein, isoflavans, rokitomicin, miltefosine/chlorpromazine, corifungin and certain amidino derivatives that showed amoebicidal effects in Naegleria cultures and conferred protection in a mouse model (Zhang et al, 1988;Belofsky et al, 2006;Kim et al, 2008a, c;Debnath et al, 2012;Rice et al, 2015).…”

Prenylated Isoflavonoids: Botanical Distribution, Structures, Biological Activities and Biotechnological Studies. An Update (1995 – 2006)

“…Amphotericin B (2.5 mg/kg/day) offered 12.5 % protection of the mice, whereas compound 65b did not protect the mice from PAM infection as compared to controls [18]. Amphotericin B (2.5 mg/kg/day) offered 12.5 % protection of the mice, whereas compound 65b did not protect the mice from PAM infection as compared to controls [18].…”

Isoflavonoids of the Leguminosae

“…20 MeOH extracts of the whole plant of Dalea aurea (golden prairie clover) yielded the known isoflavan manuifolin K together with its 7-methyl ether (98), which has not been recorded previously (note the incorrect designation of 98 as 7-methoxymanuifolin K in this study). 139 The (3S)-configuration of 98 was determined from CD measurements (positive and negative Cotton effects at 240 and 289 nm, respectively). In bioassays with Naegleria fowleri, an amoeba responsible for primary amoebic meningoencephalitis (a rare but fatal condition), both manuifolin K and 7-O-methylmanuifolin K (98) showed growth inhibition at 30 mM comparable to that of the control, amphotericin B (0.1 mM).…”

“…In bioassays with Naegleria fowleri, an amoeba responsible for primary amoebic meningoencephalitis (a rare but fatal condition), both manuifolin K and 7-O-methylmanuifolin K (98) showed growth inhibition at 30 mM comparable to that of the control, amphotericin B (0.1 mM). 139 Six prenylated isoflavans (99)(100)(101)(102)(103)(104) isolated as minor components of root extracts of Desmodium incanum (published under the synonym Desmodium canum) are 5-oxyisoflavans, which are much less frequently observed than 5-deoxyisoflavans. Although the latter is used currently to treat the disease, it is compromised by severe side-effects, emphasising a need for new drug therapies.…”

“…159 Hedysarimbenzofurans A (135) and B (136) are examples of an important group of 2-arylbenzofurans bearing a one-carbon unit at C-3. 88 MeOH extracts of the lower bark of the 'smoke tree' Psorothamnus spinosus (published under the synonym Dalea spinosa) yielded spinosans A (138) and B (139). 4 Isolated from 95% EtOH extracts of Corethrodendron multijugum (published under the synonym Hedysarum multijugum) roots, both 135 and 136 possess the uncommon 2 0 ,4 0 ,6 0 -tri-O-substitution pattern of the B-ring.…”