Date Approved

10-31-2018

Embargo Period

11-5-2018

Document Type

Thesis

Degree Name

MS Pharmaceutical Sciences

Department

Chemistry and Biochemistry

College

College of Science & Mathematics

Advisor

Jonnalagadda, Subash

Committee Member 1

Ramanjuchary, Kandalam

Committee Member 2

Mugweru, Amos

Subject(s)

Drug development; Pharmacognosy

Disciplines

Medicinal-Pharmaceutical Chemistry

Abstract

Betulin and betulinic acid are pentacyclic triterpenoid natural product isolated from the bark of birch trees. While betulin is abundantly available in the bark, betulinic acid is present in scarce quantities in nature. However, betulinic acid can be conveniently synthesized from betulin via simple redox manipulations. Betulinic acid shows selective cytotoxicity profile against cancer cells in vitro while being relatively safe for normal cells. One of the challenges for the clinical development of betulinic acid is its lack of aqueous solubility. The three key structural features of betulin/betulinic acid that have been routinely exploited for structural modifications to enhance their chemical and biological properties include C28 primary alcohol, C3 secondary alcohol, and a C20 alkene moiety.

We have been working on the functionalization of betulin for potential development as anti-cancer agents. Previously, we had reported the synthesis of betulin conjugates via reactions such as Passerini, reductive amination, and aldol condensation. Herein, we report the synthesis of betulinic acid triazole conjugates employing Baylis-Hillman and click reaction protocols as the key steps in our synthesis. The cytotoxicity evaluation of these conjugates demonstrated promising anti-cancer activity against two cancer cell lines.

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