Mitochondria-Targeting Symmetric Diiminoguanidines: Potent and Selective Anticancer Agents Against Pancreatic Tumors

Abstract

Pancreatic cancer remains one of the deadliest malignancies of the 21st century, with a five-year survival rate below 12%. Its growing incidence is strongly linked to modern lifestyles, marked by obesity, diabetes, overnutrition, and physical inactivity. Current chemotherapies offer limited success and are often burdened by severe side effects, highlighting the urgent need for more effective and selective treatments. In response, we have developed a new class of easily synthesized, amphiphilic symmetric diiminoguanidines and evaluated their antiproliferative activity against pancreatic cancer cell lines. Several compounds demonstrated remarkable efficacy and selectivity, positioning them as strong candidates for further in vivo evaluation. Fluorescence microscopy revealed that these molecules rapidly localize into mitochondria. Preliminary mechanistic studies suggest their primary target is the mitochondrial respiratory chain. These findings support the potential of diiminoguanidines as affordable, mitochondria-targeting alternatives to existing pancreatic cancer therapies.