Andrographis paniculata is an important herbal drug, it is used for cancer treatment and other various diseases. Andrographolide is the major chemical constituent of the extraction of Andrographis paniculata. It is a series of new andrographolide analogs that were designed based on structural activity relationship properties then minimized and docked against potential PI3K Inhibitor (PDB ID: 4XX5) using Schrödinger software (10.1). Docking studies of andrographolide analogs designed by substituting different chemical groups, The ligand 10(-8.885), 11(-8.808), 12(-8.415), 14(-8.133), 15(-8.079), showed high binding affinity against PI3K Inhibitor (PDB ID: 4XX5) Compared to the standard drug imatinib (-9.201). Binding affinity towards the active site of the protein. The target andrographolide analogs were evaluated for their in vitro anticancer activity against two cancer cell lines: non-small cell lung cancer A549 cell line and breast cancer MCF-7 cell line. Andrographolide analogs showed good potent anticancer activity compared with standard. These studies may pave a new way for better treatment for anticancer drugs.