2. Academic Validation
  3. Design, synthesis, and evaluation of novel heteroaromatic analogs of curcumin as anti-cancer agents

Design, synthesis, and evaluation of novel heteroaromatic analogs of curcumin as anti-cancer agents

  • Eur J Med Chem. 2014 Mar 21:75:123-31. doi: 10.1016/j.ejmech.2014.01.041.
Nawras Samaan 1,  Qiu Zhong 2,  Jayjoel Fernandez 1,  Guanglin Chen 1,  Ali M Hussain 1,  Shilong Zheng 3,  Guangdi Wang 4,  Qiao-Hong Chen 5
Affiliations

Affiliations

  • 1 Department of Chemistry, California State University, Fresno, 2555 E. San Ramon Avenue, M/S SB70, Fresno, CA 93740, USA.
  • 2 Department of Chemistry, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA.
  • 3 RCMI Cancer Research Program, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA.
  • 4 Department of Chemistry, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA; RCMI Cancer Research Program, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA.
  • 5 Department of Chemistry, California State University, Fresno, 2555 E. San Ramon Avenue, M/S SB70, Fresno, CA 93740, USA. Electronic address: [email protected].
PMID: 24531225 DOI: 10.1016/j.ejmech.2014.01.041
Abstract

To improve the potential of curcumin to treat advanced hormone-refractory prostate Cancer, three series (A-C) of heteroaromatic analogs (thirty two compounds) with different monoketone linkers have been synthesized and evaluated for cytotoxicity against two human androgen-independent prostate Cancer cell lines (PC-3 and DU-145). Among them, thirty analogs are more potent than curcumin against PC-3 cells, and twenty one analogs are more cytotoxic towards DU-145 cells relative to curcumin. The most potent compounds (44, 45, 51, and 52) also showed impressive cytotoxicity against three Other metastatic Cancer cell lines (MDA-MB-231, HeLa, and A549), with IC50 values ranging from 50 nM to 390 nM. All four most potent analogs exhibited no apparent cytotoxicity towards the MCF-10A normal mammary epithelial cells. Taken together, selective enhancement of cell death in prostate Cancer cell lines and Other aggressive Cancer cell lines suggests that nitrogen-containing heteroaromatic rings are promising bioisosteres of the substituted phenyl ring in curcumin.

Keywords

Curcumin; Cytotoxicity; Heteroaromatic analogs; Prostate cancer.

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