A Novel Approach for Overcoming Drug Resistance in Breast Cancer Chemotherapy by Targeting new Synthetic Curcumin Analogues Against Aldehyde Dehydrogenase 1 (ALDH1A1) and Glycogen Synthase Kinase-3 beta (GSK-3 beta)

作者：Kesharwani Rajesh Kumar^*; Srivastava Vandana; Singh Prabhakar; Rizvi Syed Ibrahim; Adeppa Kuruba; Misra Krishna

来源：Applied Biochemistry and Biotechnology, 2015, 176(7): 1996-2017.

DOI：10.1007/s12010-015-1696-x

• Aldehyde dehydrogenase 1
• Analogues
• Antioxidant
• Breast cancer
• Curcumin
• Docking
• Glycogen synthase kinase-3 beta
• Glide synthesis

Breast cancer stem cells are well known to resist the traditional methods like chemo and radio therapy. Aldehyde dehydrogenase 1 (ALDHIA1) and glycogen synthase kinase-3 beta (GSK-3 beta) are the two selected proteins for study, due to their overexpression and upregulation in breast cancer cells. Curcumin, the yellow pigment of the spice turmeric, is widely reported as an antioxidant and acts as a synergist along with traditional drugs. Under hypoxic conditions, it gets converted to free radical which causes apoptosis. Three naturally occurring curcuminoids, i.e. curcumin, demethoxycurcumin, and bisdemethoxycurcumin along with five derivatives/analogues of curcumin, viz. 4,4'-di-O-(carboxy-methyl)-curcumin, 4-O-(2-hydroxyethyl) curcumin, 4,4'-di-O-allyl-curcumin, 4,4'-di-O-(acetyl)-curcumin, and 3,3'-bisdemethylcurcumin were synthesized and evaluated for their anti-breast cancer potential by docking simulation and assessment of their antioxidant character, studied via 2, 2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS(center dot+)) radical cation scavenging assay, 2,2-diphenyl-1-picrylhydrazyl (DPPH center dot) radical, and ferric reducing ability potential (FRAP) assay. A co-relation between structure and activity of curcuminoids/its analogues and derivatives has been worked out.

• 出版日期2015-8