Table 5.
SAR summary of synthesized benzimidazole and benzothiazole derivatives against Hsp70 and FoxM1. The table outlines the effects of different substituents on cytotoxic activity (IC50 values) in MCF-7, HeLa, and HUVEC cell lines, highlighting structural features correlated with enhanced potency and selectivity.
| Group | Scaffold | Key Substituents | Active Site Interactions | IC₅₀ (μM) HeLa, MCF-7, HUVEC | Observed Activity |
|---|---|---|---|---|---|
| 1 | Benzimidazole | 3-F in R1 | Tyr15, Arg272, Glu268 | >100 all three | Good Hsp70 binding, moderate cytotoxicity |
| 2 | Benzimidazole | 3-Cl + propargyl | Arg272, Thr37, Asp53 | >100 all three | Improved cytotoxicity in HeLa, MCF-7 |
| 3 | Benzimidazole | 3-Me + propyl | Arg272, Thr265 | >100 all three | Moderate activity |
| 4–5 | Benzimidazole | N-propargyl/N-nitrile | π-π and covalent potential | >100 all three | Mixed activity, depends on R1 |
| 6 | Benzothiazole | 3-F + sulfonamide | Arg342, Ser340, Asp366 | 30.5, 28.1, >100 | Good Hsp70 and FoxM1 binding |
| 7 | Benzothiazole | 3-Cl + sulfabenzamide | His287, Arg286 (FoxM1); Arg272 (Hsp70) | 12.7, 10.8, 106.7 | Highest cytotoxicity (compound 7d) |