LN-405

Novel Imidazopyridines and Their Biological Evaluation as Potent Anticancer Agents

Güçlü et al. synthesized new imidazopyridine derivatives with substituents on both imidazole and pyridine rings, and then evaluated their biological activity against a glioblastoma cell line (LN-405) to explore their potential as glioblastoma candidate drugs. Analysis of the interactions between the compounds and cells showed that the most effective molecules were 5a and 5i, which exhibited potent cytotoxic activity against the LN-405 cell line (Fig. 1A). Subsequently, the effect of the 5a and 5i on the cell cycle was examined by flow cytometry. The results indicated that the percentage of LN-405 cells in the G0/G1 phase was almost the same for both compounds. While a very low percentage of the cells incubated with 75 µM of 5i were able to reach the S phase, none of the cells incubated with 10 µM of 5a were detected in the S phase. This suggests that 5a and 5i effectively inhibited DNA replication (Fig. 1B). Flow cytometry results indicated that the lead compounds 5a and 5i might have antiproliferative effects on the LN-405 cell line.

Fig. 1. (A) Cell viability after incubating LN-405 cell lines with 100 µM concentrations of compounds 5a–i. (B) Flow cytometry results for 5a and 5i (Güçlü, D., Kuzu, B., et al., 2018).

The Combination of SB and CEL Affects DNA Repair in Glioblastoma Cell Lines

Sodium butyrate (SB) is a histone deacetylase inhibitor, and celastrol (CEL), derived from the tripterygium wilfordii plant, acts as an mTOR and proteasome inhibitor. Kartal et al. discovered that SB and CEL exhibit anticancer effects in glioblastoma through DNA repair inhibition, apoptosis induction, and autophagy regulation. In the glioblastoma cell lines LN-405 and T98G, the expression levels of DNA repair genes MGMT, MLH-1, MSH-2, and MSH-6 were measured. The results showed significant differences in MGMT, MLH-1, MSH-2, and MSH-6 gene expression between the control group and the SB, CEL, and SB+CEL groups in LN-405 and T98G cell lines (Fig. 2). Additionally, in the T98G cell line, significant differences in MGMT and MLH-1 gene expression were observed between the CEL group and both the SB and SB+CEL groups (Fig. 2A and B). In the LN-405 cell line, there were significant differences in MLH-1 expression between the SB+CEL group and both the SB and CEL groups (Fig. 2B). Furthermore, significant differences in the expression of MSH-2 and MSH-6 between the SB+CEL group and both the SB and CEL groups were detected in both LN-405 and T98G cell lines (Fig. 2C and D).

Fig. 2. DNA repair gene expression levels in groups treated with SB, CEL, and SB+CEL combination in LN-405 and T98G cell lines (Kartal B, Denizler-Ebiri FN, et al., 2024).