In our previous study, a series of novel cyclic
cyanoguanidine compounds, eg. 5-substituted 2-cyanoimino-4-imidazodinone and 2-cyanoimino-4-
pyrimidinone derivatives have been successfully synthesized and showed remarkable cytotoxicity in several
cancer cell lines. In this present study, it is our aim to screen more potential candidates among the cyclic pyridyl
cyanoguanidine compounds (BPR-DC-1, 2, 3) by in vitro and in vivo studies for the
therapy of
lung cancer, alternatively. Our results showed that BPR-DC-2 significantly inhibited proliferation of
tumor cells with an IC50 of 3.60 ± 1.27 and 14.81 ± 4.23 μM in human lung
carcinoma cells, H69 and A549, respectively by the MTT assay at 48 hr; BPR-DC-2 also obviously suppressed the
tumor proliferation and MDR-1 gene expression, even induced cell apoptosis in the ex vivo histocultured lung
tumor. We further demonstrated that, in the nude mouse model of metastatic
lung cancer, BPR-DC-2 could diminish the
tumor mass, retard the progression of
metastasis, and prolong the survival time. In addition, it was found that BPR-DC-2 exerted its anti-
tumor effects through the inhibition of MDR-1 gene expression and down-regulation of
tumor anti-apoptosis signals (activated p-AKT and over-expression of PARP-1) by western blotting analysis. In conclusion, in this present study we have demonstrated that BPR-DC-2, derived from a series of novel synthetic cyclic
cyanoguanidine compounds, has proved its potential as an anti-
tumor drug candidate in treating
lung cancer.