Alkaloids ofHernandia voyronii: Chloroquine-Potentiating Activity and Structure Elucidation of Herveline D

Abstract

Further investigation of Hernandia voyronii led to the isolation of a new pavine-benzyltetrahydroisoquinoline (pavine-BTIQ) dimer, herveline D, together with herveline A, five aporphine alkaloids, two morphinane alkaloids, and their bio-synthetic precursor, i.e., the BTIQ ( S)-reticuline. Hervelines A-D have a moderate intrinsic in vitro antimalarial activity (IC (50) in the range of 1.68-3.28 microM), but displayed different effects ranging from synergism for herveline B and herveline C to simple additive effect for herveline A, and antagonism for herveline D in a chloroquine (CQ) combination evaluation and this was confirmed in vivo for hervelines A and B. Furthermore, the antiplasmoidal activity of CQ was potentiated in vitro by reticuline and its dimethyl derivative laudanosine (for the latter also in vivo), whereas herveline C moderately potentiated in vitro the anti-plasmodial activity of herveline D.

Myco-synthesis of silver nanoparticles using Metarhizium anisopliae against the rural malaria vector Anopheles culicifacies Giles (Diptera: Culicidae)

“…Research strategies to eradicate malaria, follow different approaches, including (i) the classic pharmacological treatment based on several active molecules that, according to the ''magic bullet'' paradigm, inevitably let to resistance by Plasmodium (Korsinczky et al 2000;Jensen and Mehlhorn 2009;Turschner and Efferth 2009), (ii) the use of natural products to reduce the employ of chloroquine, avoiding the insurgence of resistance (Rasoanaivo et al 1994(Rasoanaivo et al , 1998(Rasoanaivo et al , 2001Ramanitrahasimbola et al 2001), (iii) the development of a vaccine (Crompton et al 2010;Hill 2011), (iv) searching for natural mutations of Plasmodium genoma into less aggressive forms, making the host tolerant to the parasite (Reiter 2001); and (v) the control of mosquito vectors, mainly based on insecticidal treatments against mosquito larvae, with serious impact on the environment and human health (see Benelli et al 2015 for a recent review). No single strategy is fully successful.…”

Perspective in Antimalarial Chemotherapy

“…In rodents studies, however hervelines A and B, 10 mg/ kg/day for 4 days, produced only 31.8 % and 15% suppression of parasitemia against the CQ-resistant strain N67 of P. yoelii in mice. In a chloroquine combination evaluation which was confirmed in vivo for hervilines A and B, they displayed different effects, ranging from synergism for herviline B and C to a simple additive effect for herveline A and antagonism for herveline D. Further more, the antiplasmodial activity of chloroquine was potentiated by laudanosine and confirmed in vivo [14].…”

“…The differences observed between the two Plasmodium species (P. berghei and P vinckei petteri) could be related to the innate sensitivity of P.vinckei petteri [16]. In other studies, the antimalarial activity (IC 50 ) of cryptolepine, and its hydrochloride and 11-hydroxy cryptolepine (14) were in range of 27 to 62 ng/ml against D-6, K1 and W-2 strains of P. falciparum in vitro. Cryptolepine and 11-hydroxy cryptolepine (50 mg/kg/day for four days po) had a low suppressive effect (45%) against P. berghei yoelii in mice.…”

“…A number of indoloquinoline alkaloids (13)(14) have been isolated as the antimalarial principle of Cryptolepis sanguinolenta (Periplocaceae), a plant used in West Africa for the treatment of malaria. The most potent compound was cryptolepine (13, IC 50 = 0.031µg/ml) which was as active as chloroquine against P. falciparum K1 (multidrug resistant) [24].…”

Exploiting a basic chemosensitizing pharmacophore hypothesis. Part 1: Synthesis and biological evaluation of novel arylbromide and bicyclic chemosensitizers against drug-resistant malaria parasites

“…This observation is in agreement with our previous work. 17 Remarkably, isobologramme curves (Fig. 5C) depict the shift of the activity from synergistic, additive to slight antagonistic effect according to the relative position, ortho, meta, para, of the benzene ring of the biphenyl ether compounds 3.…”