Date of Award

2005

Document Type

Thesis

Department

Chemistry

First Reader

Dr. Martin D. "Marty" Perry

Second Reader

Professor Glenn Good

Third Reader

Dr. Randall Wight

Abstract

Melatonin (MLT, N-Acetyl-5-methoxytryptamine), a naturally occurring hormone produced by the pineal gland, plays a crucial role in the regulation of circadian rhythms. Melatonin supplements are utilized in treating various sleep disorders, but detrimental side effects currently discourages its use in space. Computer generated molecular models of MLT analogues were studied with the purpose of resolving the deficiencies within existing therapeutic agents by constructing an enhanced MLT analogue. The MT receptor binding data for each analogue was obtained from the literature and Sybyl 6.9 was used to perform 3-D quantitative structure-activity relationship (QSAR) studies on eight data sets, using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods. The predictive capabilities of each mathematical model were tested and structural changes, which most effectively increased the predicted activities for each set, were noted. The models consistently indicated that a steric increase of the methoxy group would improve the activity of MLT.

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