Diversity-oriented synthesis of α-aminophosphonates: A new class of potential anticancer agents

• A small library of structurally diverse α-aminophosphonates has been synthesized.
• Synthesized compounds assayed for cytotoxic activity against human cancer cell lines.
• Some of the compounds showed activity in micromolar range against some cell lines.
• One compound showed high potency (IC50 value of 4 μM) against Jurkat cell line.
• In one case, selectivity of activity of (R)- over (S)- was observed.

A small library of structurally diverse α-aminophosphonates has been synthesized by reacting alkyl/aryl aldehydes, alkyl/aryl amines and alkyl/aryl phosphites in one-pot catalyzed by Amberlite-IR 120 resin (acidic). All the synthesized α-aminophosphonates were assayed for their in vitro cytotoxic activities against a panel of five human cancer cell lines including A-549, NCI-H23 (Lung), Colo 320DM (Colon), MG-63 (Bone marrow) and Jurkat (Blood T lymphocytes). Compound 4n having (R)-1-phenylethanamine was found to be the most active amongst all the synthesized α-aminophosphonates against all the five cancer cell lines, most prominent being against Jurkat cell line with an IC50 value of 4 μM. Surprisingly, compound 4o having (S)-1-phenylethanamine was found to be devoid of any cytotoxicity. Our finding suggests that these chemical entities could further serve as interesting template for the design of potential anticancer agents.

A small library of structurally diverse α-aminophosphonates has been synthesized and assayed for cytotoxic activity against human cancer cell lines. One compound showed high potency (IC50 of 4 μM) against Jurkat.Figure optionsDownload as PowerPoint slide