الفهرس | Only 14 pages are availabe for public view |
Abstract This thesis is divided into two chapters. Chapter 1 concerns the synthesis and molecular modeling study of multitarget coumarin-based anti-breast cancer agents. While Chapter 2 illustrates the design, synthesis, and molecular dynamics analysis of novel series of coumarin sulfonates and sulfamates-based compounds as carbonic anhydrases II/ IX/ XII inhibitors, besides evaluating their anticancer activity. Methods: A new series of 7-substituted coumarin scaffolds containing a methyl ester moiety at the C4-position were synthesized through a Pechman cyclocondensation reaction involving acid-catalyzed condensation of resorcinol with ethyl 4-chloroacetoacetate to afford the starting compound 4-chloromethyl-7-hydroxycoumarin (1.56) followed by 2 steps nucleophilic substitution and benzoylation reaction, acetylation reaction or sulfonylation reaction. Results proved that compound 1.73 elicited the highest inhibitory activity (94.73% of the potency of EXM), while compounds 1.75 and 1.77 displayed 97.67% and 81.92% of the potency of Erlotinib, respectively in chapter 1. While, three compounds, 2.72, 2.73 and 2.75, showed prominent anti-proliferative activity with IC50 values of 20.68 µM, 21.15 µM and 22.06 µM, respectively concerning chapter 2. Conclusion: these potent compounds were susceptible to being modified further to serve as promising multi-targeted anti-cancer agents. |