Antiproliferative activity in vitro and antitumor effect in vivo of a new derivative of chollongdione - 2,21-bis-[2-pyridinyl]methylidene chollongdione DP-41 (2NK)

Background: Malignant neoplasms remain a leading cause of death worldwide, and chemotherapy resistance necessitates the search for new drugs with improved efficacy and safety profiles. Natural tetracyclic triterpenes, particularly those of the dammarane series, have demonstrated multifaceted pharmacological activity, including pronounced anti-inflammatory and antitumor properties, making them attractive for the development of new anticancer drugs. However, their often-limited bioavailability and limited effect stimulate research into targeted structural modifications to enhance biological activity.

Aim: To evaluate the cytotoxic activity and antitumor effect of a new arylidene derivative of chollongdione - 2,21-bis-[2-pyridinyl]methylidene chollongdione

Method: Cytotoxicity was evaluated using MTT test. Cell cycle and apoptotic activity were analyzed using flow cytometry on an ADAMII™-LS instrument. The antitumor effect was studied in vivo using HCT116 colon cancer xenograft models in Danio rerio embryos.

Result: 2,21-bis-[2-Pyridinyl]methylidenechollone longedione - Dp-41 (2NK) demonstrated cytotoxic activity in DU145 (0.7±0.03 μM), HCT116 (0.99±0.01 μM), Panc1 (0.2±0.03 μM) and A549 (0.6±0.04 μM) cell cultures, as well as antitumor activity in the HCT116 human colon cancer xenograft model in Danio rerio embryos with a TGI value of 72%.

Conclusion: Dp-41 (2NK) exhibits high antiproliferative activity against prostate, colon, pancreatic and lung cancer cells, as well as xenografts of human colon cancer HCT116 in zebrafish embryos.