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There is considerable interest in the plant family Amaryllidaceae for its biologically-active isoquinoline alkaloid principles. Some of these (such as galanthamine and narciclasine) have demonstrated their applicability in the clinical arena, particularly as cancer and motorneuron disease therapeutics. While synthetic organic chemistry affords ideal opportunities for drug development with such targets, the phytochemical approach is considered a somewhat more amenable option. In this regard, southern Africa has garnered widespread attention due to the abundance of Amaryllidaceae plants in its territory. Crinum, Ammocharis, Amaryllis, Cyrtanthus and Brunsvigia are genera of the family that are likewise well-represented in southern Africa. Up to 2012, thirty members from these genera were examined for their chemical and biological properties, culminating with the identification of nearly one-hundred alkaloid entities several of which exhibited notable biological activities. The present effort covers studies since 2013 that have been undertaken on the title genera in regards to their chemical and biological characteristics. Close to ninety alkaloids and twenty-five non-alkaloid entities were described during this time-frame from fifteen representative species. Biological studies included cholinesterase inhibiton, cytotoxicity, antidiabetes and antihypertensive effects, herbicidal, insecticidal and plant growth regulatory effects, as well as anti-inflammatory, antioxidant and antiplasmodial effects. The structural variety of the compounds isolated in cases allowed for structure-activity probes to be made in some of the assays. There were also studies carried out to establish the molecular basis to these activities, notably in the area of molecular cancer chemotherapeutics.

Stimulated by the promising results seen for its phenanthridones in clinical trials, interest in the Amaryllidaceae as a potential source of anticancer drugs has intensified in recent years. As such, over three hundred isoquinoline principles from its various alkaloid groups have to date been screened against a large number of cancer cell lines. Whilst significant effort has been diverted towards studies of lycorine and its congeners, the closely-allied homolycorine alkaloids of this plant family have largely been overlooked. These compounds have often been used as supporting acts to bolster the diversity of structures in cytotoxicity studies of the more recognized phenanthridone, lycorane and crinane alkaloids of the Amaryllidaceae. This notwithstanding, a substantial amount of information has surfaced over the past several years on such effects for the homolycorine alkaloids. This review takes a detailed look at the cytotoxic effects manifested by over forty of these alkaloids against around sixty cell lines, which may be classified into eighteen different types of cancers. In this regard, good activities were detected for some constituents (such as lycorenine and hippeastrine) against various hepatic and prostate cancers. The structural features which support and fortify the efficacy of the homolycorine alkaloid cytotoxic pharmacophore are also considered. These include the ways in which the innate ring systems are appended as well as the size, geometry and electronics of the attendant substituents. In addition, the various mechanisms used to rationalize the cytotoxic responses are described notably, interaction with DNA, apoptosis induction, protection from tumor invasion, efflux pump perturbation and topoisomerase inhibition.

From camptothecin to vinblastine, plant alkaloids continue to capture the imagination of scientists as a valuable source of anticancer drugs. Given that they are also amongst the most common secondary metabolites encountered in plants, the number of alkaloid entities subjected to cytotoxicity evaluations now runs into several thousands. Interest in the plant family Amaryllidaceae has been persistent owing to the potent cytotoxic activities of several of its isoquinoline alkaloid principles. This survey is an indepth account of such properties discernible for tazettine alkaloids belonging to the minor alkaloid groups of the Amaryllidaceae. Eleven of such compounds have up to now been screened against around 50 cancer cell lines which may be classified into nearly 20 different types of cancers. Although the activities in most instances were moderate to mild, notable responses were observed against some leukemia, adenocarcinoma, lymphoma and glioblastoma cell lines. In fact, pretazettine (ED50 0.3 μg/mL) was amongst the most potent of all Amaryllidaceae alkaloids screened against the human Molt4 T-lymphoma cell line. To most accounts, the parent compounds (such as tazettine and pretazettine) with their distinct ring systems and substitution patterns exhibit the best activities, offering little space for structural adjustments via semi-synthetic operations. Several avenues have been probed in attempts to elucidate the mechanisms by which tazettine alkaloids manifest their cytotoxic effects including, inhibition of protein synthesis, apoptosis and efflux pump interactions, the first of which to date offers the most profound insights.

There are subtle mechanisms at work in nature to maintain a balance in the interactions between plants and animals. The production of secondary metabolites is one of the key strategies utilized by plants to minimize their over-exploitation. The ‘lily borer’ moth Brithys crini poses a considerable challenge to Amaryllidaceae plants owing to the devestation it can cause during the larval stage of its development. This, despite the fact that the Amaryllidaceae is richly endowed with an assortment of isoquinoline alkaloid constituents which exhibit a diverse array of biological properties, particularly cytotoxicity-related effects. In this study, laboratory-maintained larvae of B. crini were periodically fed fresh leaves of Crinum moorei during the September to November infestation period in Pietermaritzburg, South Africa. Solvent extracts of the plant leaves, moth larvae and larvae excrement material were then prepared and subjected to HPLC and LC–MS analyses. The presence of several alkaloids, including cherylline and ambelline, in all three extracts was ratified via HR-MS and NMR analyses. The identification of ambelline is noteworthy since it has not been reported in previous studies of C. moorei. Toxicity related criteria are also considered based on the present detection of alkaloids in B. crini larvae material, as well as precedence for their association with other known insect predators of the Amaryllidaceae.

Malaria is responsible for majority of the morbidity and mortality statistics reflected by tropical diseases. Whilst effectively managed in most parts of the globe, it remains a scourge on the African continent where most cases of the disease are diagnosed annually. Plants have played a leading role as a source of malarial drugs which continue to dominate the clinical landscape today. Most if not all of these discoveries have as their basis evidence which can be traced back to traditional medicine. There is likewise precedence for the use of Amaryllidaceae plants in traditional medicinal approaches towards malaria. The chief phytochemical principles of the Amaryllidaceae are its isoquinoline alkaloids which are responsible for its diverse biological properties. These alkaloids may be divided into major and minor groups based on their distinguishing structural features as well as their natural abundance and distribution in the family. Whilst much has been written about the biological and chemical properties of the major alkaloid groups of the Amaryllidaceae, relatively little is known or understood about its minor alkaloid groups. This review focuses on the antiplasmodial activities described in the literature for the minor alkaloid group members of the Amaryllidaceae against various strains of the malarial pathogen Plasmodium falciparum . Three database platforms (Google Scholar, SciFinder and Scopus) were utilized for the literature search. Articles were accessed from journals licensed to the University of KwaZulu-Natal, or directly via the respective corresponding authors. Also considered are structural elements of these alkaloids which may be used to explain such activities as well as to provide a foundation in attempts to modulate activities. In addition, evidence is provided on the molecular basis to these effects which could guide efforts in drug discovery.

Cancer is a leading cause of death worldwide. This, in spite of the tremendous gains made in cancer chemotherapies over the past several decades. The identification and development of new targets with greater structural diversities and better potencies are at the forefront of drug discovery endeavors across disciplines. Plants have afforded a significant number of successful anticancer drugs, several of which manifest their activities by inducing apoptosis (or programmed cell death) in cancer cells. The Amaryllidaceae alkaloids have similarly distinguished themselves as potent antiproliferative agents, some at the nanomolar level, with selective apoptosis inducing effects demonstrated in a wide variety of cancer cells. The proteolytic enzymes caspases are the key effectors of the apoptotic pathways, the main function of which is, in turn, the activation of caspases. Once activated caspases set in motion an intricately choreographed cascade of events leading to eventual cell death and phagocytosis. The lycorane and crinane group of alkaloids were amongst the first of the Amaryllidaceae for which apoptosis and attendant caspase inducing effects were discovered. These have been central in ongoing efforts to unravel the mechanistic basis to the cytotoxicity of these alkaloids. This review focuses on the various caspases which have been shown to be integral in apoptosis signaling pathways mediated by lycorane and crinane alkaloids.

Representatives of the genus Cyrtanthus including Cyrtanthus contractus of the Amaryllidaceae family are widely used in African traditional medicine for the treatment of a range of ailments, including mental illness and age-related dementia. The alkaloid constituents distributed within the genus, which are chiefly responsible for the biological activity of the derived extracts, are thought to be influenced by changes in the growing environment. Natural growing populations of C. contractus were tagged and collected every 15th day of each month over a 12 month period. The ethanol bulb extracts from each of the collected samples were evaluated for total alkaloid content, cytotoxic effects, acetylcholinesterase and cyclooxygenase inhibition as well as antimicrobial activities. Some notable bioactivities were recorded for extracts collected during certain months of the year, particularly the cytotoxic effects against human cancer cell lines and enzyme inhibition (AChE and COX). The cytotoxic effects and AChE and COX enzyme inhibitory activities of extracts collected in May and September are of considerable interest. Similarly total alkaloids varied markedly from one month to the other. The bioactivity exhibited by C. contractus bulb extracts during certain months of the year, particularly in May and September, justifies the collection and use of these bulbs for treatment of the relevant ailments in traditional medicine during these periods.

The discovery of the karrikin class of plant growth regulators (PGRs) is a milestone accomplishment in plant biochemistry and physiology, with significant potential in agriculture and horticulture. These compounds have in common a fused furano-pyran ring system featuring various permutations of methyl substitution. Chief amongst these compounds is karrikinolide (KAR1), identified as the key germination stimulant present in plant-derived smoke, which together with five other closely-related structures (KAR2–KAR6) make up the karrikin class of PGRs. By contrast, the germination inhibitor 3,4,5-trimethyl-2(5H)-furanone has also been identified in plant-derived smoke. Various synthetic endeavours have been undertaken for structure–activity relationship study purposes as well as to probe the molecular mechanics of these compounds. In this study, syntheses of KAR1, KAR3 and S-KAR1 were carried out and their structures verified by X-ray crystallography. Effects on germination were measured against the inhibitor 3,4,5-trimethyl-2(5H)-furanone in Grand Rapids lettuce seeds. X-ray crystallographic data and germination promotory activity for S-KAR1 are described for the first time.

article i nfo The "large sour plum" tree Ximenia caffra Sond. (Olacaceae) is the only African representative of the genus Ximenia L., with a distribution covering East Africa, from Tanzania in the north to South Africa, as well as parts of Botswana and Namibia. It has many uses in traditional medicine, including treatment of wounds and infections as well as diarrhea, which have been verified through various pharmacological studies. Fur- thermore, the plant is also known for its nutritional and cosmetic value. Its edible fruits are known to be high in protein, potassium and vitamin C, while the seed oil, also referred to as "Ximenia oil" is rich in long chain unsaturated fatty acids and finds use as a domestic biofuel, with characteristics amenable to cosmetic development as topical applicants. Extracts of the plants are also widely used for treating sexually transmit- ted infections (STIs), which has been verified through ethnobotanical surveys and pharmacological screens. Based on these observations, X. caffra var. caffra was examined for its phytochemical composition and activity against the gonorrheal pathogen Neisseria gonorrhoeae. Initially, the leaf ethanolic extract was seen to be ac- tive (43.9% inhibition). The DCM partition of this extract (with 78.8% inhibition) was subjected to bioassay guided fractionation leading to the identification of the bisnorsesquiterpene vomifoliol which exhibited sig- nificant activity (63.1%) against N. gonorrhoeae.

Cycads are a group of slow-growing, perennial, dioecious plants which in geological times thrived during the Mesozoic era. The present worldwide complement of around 300 species is distributed through both tropical and subtropical regions of the globe, and has pronounced centres in Australia, Mexico and South Africa. These popular plants are known for their ornamental, economic, dietary and medicinal value. However, increased demand collectively from this sector, as well as decimation of large tracts of cycad populations in the wild through habitat destruction and unscrupulous collection, has precipitated a fragile conservation status for the family, with majority of its species listed as threatened by statutory bodies such as CITES and IUCN. Despite their popularity, cycads have for several centuries been known to be toxic. The plants have been shown to have carcinogenic, mutagenic, teratogenic and neurotoxic properties, and its major constituent principles macrozamin and cycasin have exhibited similar effects in model studies. Cycads are used widely in traditional medicine (TM) in South Africa and the majority of endemic species are commonly traded on local TM markets. The present study deals with the isolation of macrozamin from seed kernels of Encephalartos transvenosus and quantification of this toxic methylazoxymethanol (MAM) glycoside via HPLC in selected indigenous species.

The discovery of karrikins as the chemical constituents responsible for the germination stimulatory effects of smoke has met with widespread interest from the botanical/scientific community. Although such beneficial properties of smoke in agriculture and environmental management have been known for several centuries, it is only in the last decade that this significant discovery has been made. The karrikins comprising KAR1–KAR6 have been shown to be potent promoters of germination in numerous model studies. KAR1, the most abundant of the karrikins, has been revealed as the key germination cue present in smoke with activities as low as 100 ppt. Given the vast economic potential of these molecules as well as their low natural abundance, several strategies have been devised towards the synthesis of karrikins with the goal of elucidating structure–activity relationships. However, the targets of these structures as well as their mode of action are yet to be determined. To this end, we herein detail the first single crystal X-ray structure of KAR3 with the aim that it may provide further insights to the molecular mechanism behind this group of compounds.

The plant family Amaryllidaceae is known for its ornamental and medicinal value, as well as its unique alkaloid constituents, including several molecules of high biological interest, such as galanthamine, pancratistatin and lycorine. These plants are also used in traditional medicinal practice systems across the globe, and the taxonomy of the family is relatively well-understood. The African genus Boophone Herb. comprises two species, B. disticha (L.f.) Herb. and B. haemanthoides F.M. Leight. Much is known about the ethnobotanical, phytochemical and pharmacological properties of the wide-ranging B. disticha. In contrast, B. haemanthoides is a threatened and territorially restricted species, and its ethnobotanical usage by Khoi-San of the Northern Cape has only recently been described. During our investigation, B. haemanthoides was shown to be a novel source of the known β-crinane alkaloids distichamine, buphanidrine, buphanisine, and crinine. Of note is the presence of distichamine in B. haemanthoides, previously identified only in B. disticha, and its significance as a distinctive chemotaxonomic marker for the genus Boophone.

The ‘Lebombo cluster leaf’ Terminalia phanerophlebia (Combretaceae) is used in traditional medicine in South Africa for a host of ailments, including aches and pain, wounds and infections, gynaecological conditions, inflammation, mental illness such as epilepsy, and sexually-transmitted diseases. Based on the anti-inflammatory activity (92.4% inhibition of the cyclooxygenase enzyme COX-2) initially observed for a crude extract, stems of T. phanerophlebia were here examined for the underlying phytochemical principles. Three cholestane triterpenoids β-sitosterol, β-sitostenone and stigmast-4-ene-3,6-dione were isolated from the ethanol extract by silica gel column chromatography via gradient elution with hexane/ethyl acetate mixtures. Structure elucidation was facilitated by use of physical and spectroscopic methods, including high field 2D NMR and mass spectroscopic techniques. The crude extract as well as β-sitosterol was seen to be selective inhibitors of the cyclooxygenase enzyme COX-2. This work is of chemosystematic relevance as it represents the first isolation of β-sitostenone and stigmast-4-ene-3,6-dione from any species of Terminalia .

The ‘Oldwood’ tree Leucosidea sericea is the sole representative of the genus Leucosidea and as such occupies a botanically-privileged status within the Rosaceae of southern Africa. The use of the plant in the traditional medicinal practices of some of the indigenous people of the region has been known for over a hundred years. Amongst these, its use as a vermifuge and astringent medicine, as well as anti-inflammatory agent, amongst the Basuto and Zulu tribes has been recorded. Based on these observations, the plant was here examined for the underlying phytochemical principles which might corroborate these interesting traditional uses. In the process, the known cholestane triterpenoids β-sitosterol and β-sitostenone were isolated for the first time from stems of L. sericea and identified by physical and spectroscopic techniques. These findings provide insights to the traditional usage of the plant for inflammation related ailments.