Date of Award:

2016

Document Type:

Dissertation

Degree Name:

Doctor of Philosophy (PhD)

Department:

Chemistry and Biochemistry

Advisor/Chair:

Cheng-Wei Tom Chang

Abstract

Synthesizing bioactive small molecules by structural modification of 1,4-naphthoquinone was the primary goal of this research. Several bioactive compounds with anticancer, antifungal, and antibacterial activities were synthesized. All the synthetic protocols were optimized in such ways that do not require cumbersome purification.

First, a new protocol for the synthesis of NQM111 was developed. NQM111 is a highly potent anticancer agent developed in our laboratory, but the old protocol does not provide enough quantity for in vivo study. Therefore, a new safe and improved method was developed which provides enough quantity for in vivo study.

The second project involves the synthesis of 1,4-naphthoquinone conjugated with an aromatic group. These compounds are a highly potent anticancer agent with ~8-fold selectivity towards cancer cell lines than the non-cancer cell line. A mode of action study of this compound was identified, and it was observed that these compounds generate reactive oxygen species,which triggers apoptosis.

The final project involves the synthesis of 1,4-naphthoquinone based antifungal, and antibacterial compounds. These compounds are multi-cationic in nature with a hydrophobic tail. Six different analogs with varying hydrophobic tails were synthesized and tested for their antibacterial and antifungal activity. These compounds showed excellent activity against wide range of fungi including resistant strains.

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Included in

Chemistry Commons

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