Afeef S. Husni

Neocosmospora sp.-derived resorcylic acid lactones with in vitro binding affinity for human opioid and cannabinoid receptors.

Bioassay-guided fractionation of a fungus Neocosmospora sp. (UM-031509) resulted in the isolation of three new resorcylic acid lactones, neocosmosin A (2), neocosmosin B (3), and neocosmosin C (4). Three known resorcylic acid lactones, monocillin IV (1), monocillin II (5), and radicicol (6), were also isolated and identified. The structures of these compounds were established on the basis of extensive 1D and 2D NMR spectroscopic analysis, mass spectrometric (ESIMS) data, and X-ray crystallography. Compounds 4-6 show good binding affinity for the human opioid receptors. These findings have important implications for evaluating the potential psychoactive effects with this class of compounds.

Isolation and Pharmacological Evaluation of Minor Cannabinoids from High-Potency Cannabis sativa

Seven new naturally occurring hydroxylated cannabinoids (1-7), along with the known cannabiripsol (8), have been isolated from the aerial parts of high-potency Cannabis sativa. The structures of the new compounds were determined by 1D and 2D NMR spectroscopic analysis, GC-MS, and HRESIMS as 8α-hydroxy-Δ(9)-tetrahydrocannabinol (1), 8β-hydroxy-Δ(9)-tetrahydrocannabinol (2), 10α-hydroxy-Δ(8)-tetrahydrocannabinol (3), 10β-hydroxy-Δ(8)-tetrahydrocannabinol (4), 10α-hydroxy-Δ(9,11)-hexahydrocannabinol (5), 9β,10β-epoxyhexahydrocannabinol (6), and 11-acetoxy-Δ(9)-tetrahydrocannabinolic acid A (7). The binding affinity of isolated compounds 1-8, Δ(9)-tetrahydrocannabinol, and Δ(8)-tetrahydrocannabinol toward CB1 and CB2 receptors as well as their behavioral effects in a mouse tetrad assay were studied. The results indicated that compound 3, with the highest affinity to the CB1 receptors, exerted the most potent cannabimimetic-like actions in the tetrad assay, while compound 4 showed partial cannabimimetic actions. Compound 2, on the other hand, displayed a dose-dependent hypolocomotive effect only.

Secondary Metabolites from Eupenicillium parvum and Their in Vitro Binding Affinity for Human Opioid and Cannabinoid Receptors

Phytochemical investigation of the soil microfungus Eupenicillum parvum led to the isolation of two new compounds: a chromone derivative euparvione (1) and a new mycophenolic derivative euparvilactone (2), as well as thirteen known compounds. The structures of the new compounds were elucidated by means of extensive IR, NMR, and MS data and by comparison of data reported in the literature. The structure of the known compound 6 was confirmed by X-ray crystallography. Several isolated compounds were evaluated for in vitro binding assays using opioid receptors (subtypes δ, κ, and µ) and cannabinoid receptors (CB1 and CB2). Compound 10 displayed the best selective µ-opioid receptor and CB1 receptor binding affinities showing values of 47% and 52% at a 10 µM concentration, respectively. These findings provide insight into the potential therapeutic utility of this class of compounds.

Evaluation of phytocannabinoids from high-potency Cannabis sativa using in vitro bioassays to determine structure–activity relationships for cannabinoid receptor 1 and cannabinoid receptor 2

Cannabis has been around for thousands of years and has been used recreationally, medicinally, and for fiber. Over 500 compounds have been isolated from Cannabis sativa with approximately 105 being cannabinoids. Of those 105 compounds, Δ9-tetrahydrocannabinol has been determined as the primary constituent, which is also responsible for the psychoactivity associated with Cannabis. Cannabinoid receptors belong to the large superfamily of G protein-coupled receptors. Targeting the cannabinoid receptors has the potential to treat a variety of conditions such as pain, neurodegeneration, appetite, immune function, anxiety, cancer, and others. Developing in vitro bioassays to determine binding and functional activity of compounds has the ability to lead researchers to develop a safe and effective drug that may target the cannabinoid receptors. Using radioligand binding and functional bioassays, a structure–activity relationship for major and minor cannabinoids was developed.

Heteroatom analogues of hydrocodone: synthesis and biological activity.

Heteroatom analogues of hydrocodone, in which the N-methyl functionality was replaced with oxygen, sulfur, sulfoxide, and sulfone, were prepared by a short sequence from the ethylene glycol ketal of hydrocodone; a carbocyclic analogue of bisnorhydrocodone was also prepared. The compounds were tested for receptor binding and revealed moderate levels of activity for the sulfone analogue of hydrocodone.