Synthesis and Cytotoxic Activities of a Curcumin Analogue and Its bis-Mannich Derivatives


Yerdelen K. O. , GÜL H. İ. , Sakagami H., Umemura N., Sukuroglu M. K.

LETTERS IN DRUG DESIGN & DISCOVERY, vol.12, no.8, pp.643-649, 2015 (Journal Indexed in SCI) identifier identifier

  • Publication Type: Article / Article
  • Volume: 12 Issue: 8
  • Publication Date: 2015
  • Doi Number: 10.2174/1570180812666150213225134
  • Title of Journal : LETTERS IN DRUG DESIGN & DISCOVERY
  • Page Numbers: pp.643-649

Abstract

Mannich bases (2-6) of curcumin analogue 1, [1,5-bis(4-hydroxy-phenyl) penta-1,4-dien-3-one], were synthesized. Their cytotoxicity against human HL-60 promyelocytic leukemia and HSC-2, HSC-3, and HSC-4 oral squamous carcinoma cell lines, as well as against normal oral cells was evaluated. Mannich bases 2-5 displayed more potent cytotoxicity than curcumin and curcumin analogue 1 towards malignant cells with high PSE values (93.7-136.6). PARP1 cleavage assay demonstrated the induction of apoptosis of HSC-2 cells by the most potent and tumor selective compound 4, which is a bis Mannich base having N-methyl piperazine moieties. The results obtained suggest that preparation of Mannich bases of a curcumin analogue 1 was a useful chemical modification for cytotoxicity and tumour-selectivity for the compounds synthesized, and apoptosis can be one of the possible mechanisms of action for the cytotoxicity.