Design and synthesis of novel 1,2,3-triazole derivatives of coronopilin as anti-cancer compounds

• New triazolyl coronopilin derivatives synthesized from parthenin by click chemistry.
• Many coronopilin analogues exhibited significant in vitro cytotoxicity.
• Compound-3a exhibited IC50 of 3.1 against PC3 cell lines.
• Compounds showed dose dependent increase in sub G1 apoptotic phase and inhibit NF-κB.

A series of 1,2,3-triazole coronopilin congeners have been designed and synthesized by employing click chemistry approach starting from parthenin and evaluated for their cytotoxicity against a panel of six human cancer cell lines (PC-3, THP-1, HCT-15, HeLa, A-549 and MCF-7). While many compounds exhibited significant anticancer activity, compound 3a, was found to be the most promising analogue in this series with IC50 values of 3.1 μM on PC-3 cell line. Flow-cytometric studies showed that 1,2,3-triazole derivative-3a induce dose dependent apoptosis in the sub G1 phase. This lead molecule-3a was further studied for NF-κB (p65) transcription factor inhibitory activity using Elisa and western blotting analysis which confirmed concentration dependent inhibitory activity against NF-κB, p65 with 80% inhibition in 24 h at 100 μM.

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