Bioassay-guided isolation and identification of gametocytocidal compounds from Artemisia afra (Asteraceae)

Abstract

Background Optimal adoption of the malaria transmission-blocking strategy is currently limited by lack of safe and efficacious drugs. This has sparked the exploration of different sources of drugs in search of transmission-blocking agents. While plant species have been extensively investigated in search of malaria chemotherapeutic agents, comparatively less effort has been channelled towards exploring them in search of transmission-blocking drugs. Artemisia afra (Asteraceae), a prominent feature of South African folk medicine, is used for the treatment of a number of diseases, including malaria. In search of transmission-blocking compounds aimed against Plasmodium parasites, the current study endeavoured to isolate and identify gametocytocidal compounds from A. afra . Methods A bioassay-guided isolation approach was adopted wherein a combination of solvent–solvent partitioning and gravity column chromatography was used. Collected fractions were continuously screened in vitro for their ability to inhibit the viability of primarily late-stage gametocytes of Plasmodium falciparum (NF54 strain), using a parasite lactate dehydrogenase assay. Chemical structures of isolated compounds were elucidated using UPLC-MS/MS and NMR data analysis. Results Two guaianolide sesquiterpene lactones, 1α,4α-dihydroxybishopsolicepolide and yomogiartemin, were isolated and shown to be active (IC 50 < 10 μg/ml; ~ 10 μM) against both gametocytes and intra-erythrocytic asexual P. falciparum parasites. Interestingly, 1α,4α-dihydroxybishopsolicepolide was significantly more potent against late-stage gametocytes than to early-stage gametocytes and intra-erythrocytic asexual P. falciparum parasites. Additionally, both isolated compounds were not overly cytotoxic against HepG2 cells in vitro. Conclusion This study provides the first instance of isolated compounds from A. afra against P. falciparum gametocytes as a starting point for further investigations on more plant species in search of transmission-blocking compounds. Electronic supplementary material The online version of this article (10.1186/s12936-019-2694-1) contains supplementary material, which is available to authorized users.

Chemogenomic Fingerprints Associated with Stage-Specific Gametocytocidal Compound Action against Human Malaria Parasites

“…The majority of antimalarial compounds with activity against asexual parasites will retain activity on early-stage gametocytes at a comparable level (or with some loss in activity), but those that then do have activity on late-stage gametocytes are typically characterized by an ∼10-fold loss in activity. , However, evidence is accumulating where compounds are identified with some selectivity toward gametocytes, and with higher potency against these stages than against asexual stage parasites. While this has been shown for diverse chemotypes, ,,, it also holds true for compounds with different chemotypes within the kinase inhibitor space. , Such stage-selective phenotypes have been the topic of much discussion and could be the result of either differences in uptake between asexual stage parasites and gametocytes or differences in target or target availability. Interestingly, a compound like MMV666810 shares some similarity in the core structure with MMV390048, yet it is more potent on late-stage gametocytes compared to early-stage gametocytes.…”

Toxicological, Bioassay-Guided Fractionation and Antibacterial Activity of Methanol Stem Extract of Terminalia microptera on Oral Bacteria Pathogens

“…The variation in the zones of inhibition between the crude (Table 6), partitioned fraction (Table 8), and fractions obtained from the column (Table 10) may be due to a decrease in the concentration of the phytochemical constituents' present in these fractions as the purification processes progress. It is worthy of note to remember that fractionation does not in all instances increase the level of activity as some of these phytochemicals act in synergy to produce better activity than when acting independently 43,60 .…”

Contemporary exploitation of natural products for arthropod-borne pathogen transmission-blocking interventions

“…Another gametocytocidal guaianolide sesquiterpenoid, 1α,4α -dihydroxybishopsolicepolide ( 54 ), was recently isolated from a South African plant of Asteraceae family Artemisia afra (Asteraceae). Compared to its activity against early gametocytes, compound 54 was demonstrated to exert better cidal activity against the late-stage IV/V gametocytes (IC 50 6.3 µM) [ 127 ]. This is however in contrast to derivatives of artemisinin from Artemisia annua (Asteraceae): dihydroartemisinin (DHA), artemether and artesunate with relatively poor activity against late-stage IV/V gametocytes [ 128 ].…”