Cancer remains one of the most problematic challenges in the modern medical field. Protein kinase C (PKC) is a key regulatory enzyme that drives cell growth, division, and proliferation; although its mutation develops and progresses the growth of numerous cancers, making it a promising candidate for activity inhibition. This project focused on the synthesis of novel ligands as PKC inhibitors. The computational binding interactions of the ligands with PKC were studied. Several ligands were successfully synthesized confirmed by using spectroscopic analysis. Compounds with hydrogen bond donor and acceptor substituents at both termini exhibited high potential for PKC inhibitory activity.