A series of 24 novel nitrogen-, oxygen-, and sulfur-containing heterocyclic derivatives were synthesized and evaluated for their antioxidant potential, PDK-1 and LDHA inhibitory activity, and cytotoxic effects against LoVo and HCT-116 colon carcinoma cell lines, alongside safety profiling in normal HUVECs. The gene discussed is PDK1; the disease is colon carcinoma.