Thesis Abstract
Lawsone (2-hydroxynaphthalene-1,4-dione) is a natural product that shows significant biological activity. The National Cancer Institute (NIH, United State) disclosed the lawsone skeleton that contains the quinone moiety as a precursor for clinically cytotoxic activity. Lawsone has interesting pharmacological performance, particularly as antitumor, antimicrobial, anti-parasite (Trypanosoma cruzi), and Leishmanicidal activity, anti-lung cancer. Therefore, three different approaches were taken in the synthetic approach. The first approach was based on the synthesis of naphthoquinone annulation that was synthesized from the reaction of 2 with different bi-nucleophilic reagents via Michael addition followed by intramolecular condensation. The second approach was based on the synthesis of new α-lapachone analogs during the cyclo-condensation reaction of 1 with α,β-unsaturated ketones. The third approach was based on the synthesis of novel spiro lawsone-ring skeletons, which focuses on the synthesis of spiro lawsone ring skeletons by Claisen-Schmidt condensation of 1 with some selected advanced reagents. Pharmacological studies of the synthetic compounds provided an indication of biological activities, including effects against hepatocellular carcinoma (HePG-7) and mammary gland breast cancer (MCF-7). The molecular structures of some molecules were examined by using DFT calculations.