Synthesis and Cytotoxicities of 2-[4-hydroxy-(3,5-bis-aminomethyl)- benzylidene]-indan-1-ones

Title:Synthesis and Cytotoxicities of 2-[4-hydroxy-(3,5-bis-aminomethyl)- benzylidene]-indan-1-ones

Volume: 12 Issue: 10

Author(s): Mehtap Tugrak, Halise Inci Gul and Hiroshi Sakagami

Affiliation:

Keywords: Indan-1-one, phenol, bis-Mannich bases, cytotoxicity, synthesis, tumour selectivity, chalcone analogue.

Abstract: Chalcones and Mannich bases are bioactive compounds and known with their cytotoxicities. α,β-Unsaturated ketones are reported with their alkylating potential to cellular thiols thereby inducing cytotoxicities. In this study; Mannich bases (MT2-MT7), which may generate two additional alkylating centers comparing with starting compound 2-(4-hydroxybenzylidene)-2,3-dihydroinden-1- one MT1, were designed and synthesized expecting the increased cytotoxicities in bis Mannich bases. Their cytotoxicities were tested against Ca9-22, HSC-2, HSC-3, and HSC-4 human oral squamous cell carcinoma as tumour cell lines and HGF, HPC, and HPLF human normal oral cells as non tumour cell lines. Amine parts were changed as N-methylpiperazine (MT2), pyrrolidine (MT3), morpholine (MT4), piperidine (MT5), dimethylamine (MT6), and dipropylamine (MT7).

As conclusion, Mannich bases prepared showed higher cytotoxicity and slightly reduced tumor-specificity than starting compound MT1. The results of stability studies with MT1, which is a chalcone analogue, and MT2, which is a Mannich base, suggested that the mechanism of action for the cytotoxicities of the compounds can be different from thiol alkylation in contrast to our expectation since it was not obtained any thiol adduct by stability study. However, the Mannich bases MT3, MT5, MT6, and MT7 showed tumour selectivity (TS) values higher than 1 and this suggests that they can be candidate compounds for further studies.

Cite this article as:

Tugrak Mehtap, Inci Gul Halise and Sakagami Hiroshi, Synthesis and Cytotoxicities of 2-[4-hydroxy-(3,5-bis-aminomethyl)- benzylidene]-indan-1-ones, Letters in Drug Design & Discovery 2015; 12 (10) . https://dx.doi.org/10.2174/1570180812666150430002002