title: 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 β (GSK-3β).
abstract: 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 β (GSK-3β) 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(·+)) radical cation scavenging assay, 2,2-diphenyl-1-picrylhydrazyl (DPPH·) 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.
authors.affiliation: Indian Institute of Information Technology, Allahabad, 211012, India, rajiiita06@gmail.com.
authors.forename: Rajesh Kumar
authors.initials: RK
authors.lastname: Kesharwani
authors.forename: Vandana
authors.initials: V
authors.lastname: Srivastava
authors.forename: Prabhakar
authors.initials: P
authors.lastname: Singh
authors.forename: Syed Ibrahim
authors.initials: SI
authors.lastname: Rizvi
authors.forename: Kuruba
authors.initials: K
authors.lastname: Adeppa
authors.forename: Krishna
authors.initials: K
authors.lastname: Misra
mesh_terms: D000080924:Aldehyde Dehydrogenase 1 Family; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy*; D003474:Curcumin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D038362:Glycogen Synthase Kinase 3 / Q000737:chemistry / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism*; D062105:Molecular Docking Simulation; D058990:Molecular Targeted Therapy / Q000379:methods*; D011487:Protein Conformation; D050697:Retinal Dehydrogenase / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D007527:Isoenzymes; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D003474:Curcumin