Anthelmintic Activity of Aporphine Alkaloids from Cissampelos capensis

Abstract

Two known aporphine alkaloids, (S)-dicentrine (1) and (S)-neolitsine (2), have been isolated from the MeOH extract of the aerial parts of Cissampelos capensis (Menispermaceae). The structures of these compounds were elucidated by NMR and MS analysis and comparison to literature data. These compounds were isolated by bioassay-guided fractionation using the Haemonchus contortus larval development assay. Compounds 1 and 2 exhibited EC90 values (concentration at which 90% loss of larval motility is observed) of 6.3 and 6.4 microg/mL, respectively. In an IN VIVO assay, administration of 1 resulted in 67% reduction of worm counts in mice at 25 mg/kg when dosed orally.

Nematotoxicity of drupacine and a Cephalotaxus alkaloid preparation against the plant‐parasitic nematodes Meloidogyne incognita and Bursaphelenchus xylophilus

“…Mammalian parasites have also been successful targets of naturally occurring alkaloids, e.g. quinoline alkaloids vs. Haemonchus contortus , the oxindole alkaloid paraherquamide vs. H. contortus and Trichostrongylus colubriformis , the aromatic pentacyclic alkaloid plakinidine vs. Nippostrongylus brasiliensis , brominated alkaloids vs. H. contortus , a quinolone vs. Teladorsagia circumcincta , and isoquinoline alkaloids vs. two species of Strongyloides . Similarly, activity of alkaloids against phytoparasitic nematodes has been described, e.g.…”

Pharmacological profiling an abundantly expressed schistosome serotonergic GPCR identifies nuciferine as a potent antagonist

“…A clinically well-known example is apomorphine, a synthetic morphine derivative used clinically as an anti-Parkinsonian agent due to efficacy at dopaminergic GPCRs. Several aporphine compounds have previously been demonstrated to impair neuromuscular function in a variety of helminth parasites (Ayers et al., 2007, Chan et al., 2014, Lin et al., 2014), although the molecular target of these drugs in parasites is uncharacterized. The affinity of aporphinoids for mammalian 5-HT GPCRs (Munusamy et al., 2013, Ponnala et al., 2014, Ponnala et al., 2015, Farrell et al., 2016) was especially intriguing to us in this context.…”

Evaluation of structural effects on 5-HT2A receptor antagonism by aporphines: Identification of a new aporphine with 5-HT2A antagonist activity

“…1–8 As central nervous system (CNS) receptor ligands, aporphines have been found to possess high affinity for a number of dopamine receptors (predominantly D 1 and D 2 ), 9–12 serotonin (5-HT) receptors 13–15 and α-adrenergic receptors. 6,16 Furthermore, aporphines are known with both agonist and antagonist activity at neuroreceptor sites.…”