Azobenzene derivatives show anti-cancer activity against pancreatic cancer cells only under nutrient starvation conditions via G0/G1 cell cycle arrest

Pancreatic cancer is one of the most aggressive cancers with a poor prognosis. Previous studies suggested that nutrient-deprived conditions may play a critical role in pancreatic cancer cell survival and resistance to chemotherapy. We describe a novel series of azobenzene derivatives including (E)-1-(4-methyl-3-((2-methyl-5-(naphthalen-1-yl)phenyl)diazenyl)phenyl)naphthalen-2-ol (9) with efficacy and selectivity in nutrient-deprived conditions. Although anticancer drug 5-fluorouracil (5-FU) was ineffective under nutrient-deprived conditions, five of our designed compounds, 9 and four other related compounds 11–14, showed anticancer activity with IC50 values ranging from 1.5 to 9.6 μM. Interestingly, only 9 showed no cytotoxicity in normal conditions. This selectivity profile of 9 is clearly opposite to that of 5-FU. Furthermore, cell cycle analysis showed that, in contrast to S phase arrest induced by 5-FU, 9 caused G0/G1 phase arrest, which might block cancer cell growth by arresting them in quiescence. Therefore, it could be a novel and promising candidate for effective pancreatic cancer treatment under nutrient-deprived conditions. [Display omitted] •Nutrient-deprived conditions (NDC) may play a critical role in pancreatic cancer cell survival and resistance to chemotherapy.•Syntheses of a series of azobenzene derivatives including (9) are described.•5 Azo derivatives showed anticancer activity with IC50 values ranging from 1.5 to 9.6 μM with efficacy and selectivity in NDC.•In contrast anticancer drug 5-fluorouracil (5-FU) was ineffective under NDC. Only 9 showed no cytotoxicity in normal conditions.•Cell cycle analysis showed that, in contrast to S phase arrest induced by 5-FU, 9 caused G0/G1 phase arrest.