Date of Award

2014

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Pharmaceutical Sciences

First Advisor

Navindra P. Seeram

Abstract

Iresine celosia L. is a traditional medicine used by the indigenous Mayan people for a variety of ailments. It is also the sole active ingredient in the Odyliresin™ formulation currently marketed to humans worldwide as an antioxidant and for the promotion of prostate health. However, Odyliresin™ has not been characterized phytochemically, or evaluated biologically for its intended use. This work represents the first comprehensive phytochemical investigation of the Odyliresin™ formulation botanical extract. To better understand its constitutive phytochemistry, a tailored isolation scheme was developed, using various chromatography resins (silica gel, LH-20), separation and purification techniques. In all, eleven compounds were isolated from the extract. Relevant marker compounds were isolated and characterized using HR-MS, NMR, HPLCUV, FT-IR and CD spectroscopy. These marker compounds were then quantified, analytical methods developed, and analytical fingerprint profiles generated to standardize formulation extracts. Among the compounds isolated, a novel pair of cyclic guanidine alkaloids is reported. To our knowledge, this is the second reporting of 2-substituted imidazoline alkaloids isolated from a plant source. These compounds were screened in silico for their ability to bind to the human androgen receptor (AR), a target for anti-androgen prostate cancer therapies, and further tested for their biological activity in AR-positive (LNCaP) and ARnegative (PC3) prostate cancer cell lines. These compounds show activity against AR-positive LNCaP cells in the 12.5-50 μM range, while AR-negative PC3 cells were unaffected. In addition, compounds isolated from Iresine celosia L. were screened using drug metabolism and toxicology simulation studies in silico, to predict the formation of reactive metabolites and their possible toxicological endpoints using Simulation’s Plus ADMET Predictor proprietary software. The isolation and structure elucidation of eleven compounds from the formulation, two of which are new, the development of analytical methods to quantify their presence within the extract, and initial in silico toxicology screening offer information that can be used to support a level of quality production and a reasonable expectation of safety when using this dietary supplement as directed for the promotion of prostate health.

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