Imidazopyridine linked triazoles as tubulin inhibitors, effectively triggering apoptosis in lung cancer cell line.

A library of new imidazopyridine linked triazole hybrid conjugates (8a-r) were designed, synthesized and evaluated for their cytotoxicity against four cancer cell lines namely, human lung (A549), human prostate (DU-145), human colon (HCT-116) and breast (MDA-MB 231) cancer. These conjugates exhibited good to moderate activity against the tested human cancer cell lines. Two of the conjugates (8g and 8j) showed significant antitumor activity against human lung cancer cell line (A549) with IC50 values of 0.51 µM and 0.63 µM respectively. Flow cytometry analysis revealed that these conjugates arrested the cell cycle at G2/M phase in human lung cancer cell line (A549). Immune-histochemistry and tubulin polymerization assay suggest inhibition of tubulin. Hoechst staining, annexin V and DNA fragmentation by tunnel assay suggested that these compounds induce cell death by apoptosis. Overall, the current study demonstrates that the synthesis of imidazopyridine linked triazole conjugates as promising anticancer agents causing G2/M arrest and apoptotic-inducing ability.

Development of pyrrolo[2,1-c][1,4]benzodiazepine ß-glucoside prodrugs for selective therapy of cancer.

Cancer chemotherapy has several limitations such as often insufficient differentiation between malign tissue and benign tissue. The clinical utility of the pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) are inadequate because of the lack of selectivity for tumor tissues, high reactivity of the pharmacophoric imine functionality, low water solubility, and stability. To address these limitations two new ß-glucoside prodrugs of PBDs have been synthesized and evaluated for their potential use in selective therapy of solid tumors by ADEPT. The preliminary studies reveal the prodrugs are much less toxic compared to the parent moieties. These prodrugs are activated by ß-glucosidase to produce the active cytotoxic moiety signifying their utility in ADEPT of cancer. The prodrugs 1a and 1b were evaluated for their cytotoxic activity in three human cancer cell lines, i.e., A375, MCF-7 and HT-29 by employing MTT assay. The results reveal that the prodrugs have shown significant cytotoxic activity in the presence of enzyme. Another important property of these molecules is their enhanced water solubility and stability, which are essential for a molecule to be an effective drug.