The effect of delta-9-tetrahydrocannabinol and cannabidiol on p50 of the oxygen haemoglobin dissociation curve.

Cannabis is one of the most chemically complex plants containing a large number of compounds, among which are cannabinoids; the main biologically active constituents of the plant. Delta-9-tetrahydrocannabinol (THC) is known as the main psychoactive cannabinoid. Studies have shown that the effects of THC can be modulated by cannabidiol (CBD), another major cannabinoid which has several beneficial effects of its own. This study aims to look at the effect of different concentrations of THC and CBD separately and in combination on the release of oxygen from erythrocytes by measuring the p50 of the oxygen haemoglobin dissociation curve. Blood samples were collected from twenty four healthy adult male and female non-smokers. P50 values were measured using the Hemox Analyzer for different concentrations (0, 2.5, 25, 50 and 100 ng/ml) of THC and CBD respectively, as well as with combinations of THC and CBD in 4:1 and 1:1 ratios. The results indicate that there is a decrease in P50 with increasing concentrations of both THC and CBD separately and in combination. The decrease in P50 was significant (p < .05) at all concentrations of THC and CBD. The changes observed with increasing concentrations of both THC and CBD suggests that they have an increased affinity for oxygen. This may have implications for individuals who consistently use cannabis.

Synthesis of substituted 1,3-diesters of glycerol using wittig chemistry.

1,3-di-O-Cinnamoyl-glycerol is a natural compound isolated from a Jamaican medicinal plant commonly referred to as Ball moss (Tillandsia recurvata). The synthesis of this compound was achieved via a Wittig chemistry process. The synthetic approach started with acylation of a di-protected glycerol with cinnamoyl chloride, deprotection of the glycerol moiety, reaction of the primary alcohol with bromo acetylbromide followed by treatment with triphenyl phosphine to give the corresponding phosphonium bromide. The phosphonium bromide was then converted in situ to the Wittig reagent which is the basis for a novel route to 1,3-di-O-cinnamoyl glycerol. Four analogs were also synthesized, three of which are new and are being reported in this article for the first time. The new compounds include 3-(3,4-diemthoxy-phenyl)-acrylic acid 2-hydroxy-3-(3-ptolyl-acryloyloxy)-propyl ester (3), 2-acetoxy-5-((E)-3-(3-((E)-3-(3,4-dimethoxyphenyl)acryloyloxy)-2-hydropropoxy)-3-oxoprop- 1-enyl)benzoic acid (4) and 4-((E)-3-(3-((E)-3-(3,4-dimethoxyphenyl)acryloyloxy)-2-hydropropoxy)-3-oxoprop-1-enyl)benzoic acid (5). The compounds showed no activity in our anticancer assay.

Antileukemic activity of Tillandsia recurvata and some of its cycloartanes.

BACKGROUND: Approximately 250,000 deaths were caused by leukemia globally in 2012 and about 40%-50% of all leukemia diagnoses end-up in death. Medicinal plants are a rich source for the discovery of new drugs against leukemia and other types of cancers. To this end, we subjected the Jamaican ball moss (Tillandsia recurvata) and its cycloartanes, as well as some analogs, to in vitro screening against a number of leukemia cell lines. The WST-1 anti-proliferation assay was used to determine the anticancer activity of ball moss and two cycloartanes isolated from ball moss and four of their analogs against four leukemia cell lines (HL-60, K562, MOLM-14, monoMac6). Ball moss crude methanolic extract showed activity with a 50% inhibition concentration (IC50) value of 3.028 µg/ml against the Molm-14 cell line but was ineffective against HL-60 cells. The six cycloartanes tested demonstrated varying activity against the four leukemia cancer cell lines with IC50 values ranging from 1.83 µM to 18.3 µM. Five out of the six cycloartanes demonstrated activity, while one was inactive against all four cell lines. The preliminary activity demonstrated by the Jamaican ball moss and its cycloartanes against selected leukemia cell lines continues to throw light on the broad anticancer activity of ball moss. Further studies to evaluate the efficacy of these molecules in other leukemia cell lines are required in order to validate the activity of these molecules, as well as to determine their mechanisms of action and ascertain the activity in vivo in order to establish efficacy and safety profiles.

Cycloartane-3,24,25-triol inhibits MRCKα kinase and demonstrates promising anti prostate cancer activity in vitro.

BACKGROUND: Given the high occurrence of prostate cancer worldwide and one of the major sources of the discovery of new lead molecules being medicinal plants, this research undertook to investigate the possible anti-cancer activity of two natural cycloartanes; cycloartane-3,24,25-diol (extracted in our lab from Tillandsia recurvata) and cycloartane-3,24,25-triol (purchased). The inhibition of MRCKα kinase has emerged as a potential solution to restoring the tight regulation of normal cellular growth, the loss of which leads to cancer cell formation. METHODS: Kinase inhibition was investigated using competition binding (to the ATP sites) assays which have been previously established and authenticated and cell proliferation was measured using the WST-1 assay. RESULTS: Cycloartane-3,24,25-triol demonstrated strong selectivity towards the MRCKα kinase with a Kd50 of 0.26 µM from a total of 451 kinases investigated. Cycloartane-3,24,25-triol reduced the viability of PC-3 and DU145 cell lines with IC50 values of 2.226 ± 0.28 µM and 1.67 ± 0.18 µM respectively. CONCLUSIONS: These results will prove useful in drug discovery as Cycloartane-3,24,25-triol has shown potential for development as an anti-cancer agent against prostate cancer.

Kinase inhibition by the Jamaican ball moss, Tillandsia recurvata L.

BACKGROUND: This research was undertaken in order to investigate the inhibitory potential of the Jamaican ball moss, Tillandsia recurvata against several kinases. The inhibition of these kinases has emerged as a potential solution to restoring the tight regulation of normal cellular growth, the loss of which leads to cancer cell formation. MATERIALS AND METHODS: Kinase inhibition was investigated using competition binding (to the ATP sites) assays, which have been previously established and authenticated. RESULTS: Four hundred and fifty one kinases were tested against the Jamaican ball moss extract and a dose-response was tested on 40 kinases, which were inhibited by more than 35% compared to the control. Out of the 40 kinases, the Jamaican ball moss selectively inhibited 5 (CSNK2A2, MEK5, GAK, FLT and DRAK1) and obtained Kd(50)s were below 20 µg/ml. CONCLUSION: Since MEK5 and GAK kinases have been associated with aggressive prostate cancer, the inhibitory properties of the ball moss against them, coupled with its previously found bioactivity towards the PC-3 cell line, makes it promising in the arena of drug discovery towards prostate cancer.