Structural Modification of Andrographolide Based on the Andrographolide-Irinotecan Interaction

Colon cancer remains to be the top reason to threaten the human health. Irinotecan is the first-line anti-colon cancer drug, and andrographolide derivatives are potential drug candidates for colon cancer therapy. The recent study aims to guide the development of andrographolide derivatives to treat colon cancer. In vitro incubation mixture was used to evaluate the inhibition of andrographolide derivatives towards the glucuronidation of SN-38 which is the active metabolite of irinotecan, and in silico docking method was used to explain the inhibition capability. The results showed no influence of the introduction of phenyl ring into the north group, and further introduction of methoxy group into the phenyl ring. In contrast, the introduction of bromine atom into the phenyl ring can significantly strengthen the inhibition activity towards the glucuronidation of SN-38. This kind of difference was attributed to the formation of more hydrogen bonds. In conclusion, structural modification of andrographolide based on the andrographolide-irinotecan interaction was performed to find the key structural properties for andrographolide-irinotecan interaction, guiding the R&D of andrographolide derivatives to treat colon cancer.