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)
Kesharwani R.K.,Indian Institute of Information Technology Allahabad |
Singh P.,Allahabad University |
Rizvi S.I.,Allahabad University |
Adeppa K.,India Pesticides Ltd |
Misra K.,Indian Institute of Information Technology Allahabad
Applied Biochemistry and Biotechnology | Year: 2015
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. © 2015, Springer Science+Business Media New York.
Karteek S.D.,Koneru Lakshmaiah College of Engineering |
Rao M.V.B.,Krishna University |
Yeggoni D.P.,University of Hyderabad |
Adeppa K.,India Pesticides Ltd |
And 2 more authors.
Der Pharma Chemica | Year: 2015
The salient features of core structure of coumarin template was helped in designing and synthesizing new analogs. Ample studies have proved that naturally occurring as well as the chemically synthesized coumarin analogs exhibit potent AChE inhibitory activity . It has been well reported that coumarins primarily interact with PAS of AChE. The AChE degrades the neurotransmitter acetycholine into choline and an acetate. Any molecule which inhibits breaking of acetylcholine is considered as potent AChE inhibitors[3,4]. Efforts have been made by scientists in synthesizing dual inhibitors of AChE by incorporating a catalytic site interacting moiety with coumarin by introducing different chemical groups at various positions. The present work mainly discusses the development in the area of design and synthesis of new coumarin derivatives as AChE inhibitors.After thorough screening of chemical and structural features of AD related drugs along with biological importance of coumarins and its derivatives, some novel 2-iso propyl amino derivatives of 7-methoxy coumarin were designed and synthesized. The chemical synthesis of compounds were characterized and finally docked into target protein acetyl cholinesterase(PDB No.1N5R). The docking studies have confirmed that, out of 23 compounds 17 compounds have shown remarkable binding with active site of AChE which is in-par with the standard AD drugs Rivastigmine[5,6] and Tacrine[7,8].This study heled us to understand the binding mechanism.
Manidhar D.M.,Sri Venkateswara University |
K. Uma Maheswara Rao,Sri Venkateswara University |
C. Suresh Reddy,Sri Venkateswara University |
Ch. Syamasunder,Sri Venkateswara University |
And 3 more authors.
Research on Chemical Intermediates | Year: 2012
A convenient procedure has been developed for preparation of aminesubstituted or monomethylamine-substituted alkyl/arylurea derivatives. The method comprises two steps-reaction of an alkyl/aryl amine with chlorocarbonylsulfenyl chloride in a non-polar solvent to produce an alkyl/arylcarbonylsulfenyl chloride, then reaction of this alkyl/ arylcarbonylsulfenyl chloride with ammonia or monomethylamine in a two-phase reaction with a phase-transfer catalyst, to produce the corresponding alkyl/aryl-substituted urea. © Springer Science+Business Media B.V. 2012.
Darla M.M.,Sri Venkateswara University |
Krishna B.S.,Sri Venkateswara University |
Umamaheswara Rao K.,Sri Venkateswara University |
Reddy N.B.,Sri Venkateswara University |
And 5 more authors.
Research on Chemical Intermediates | Year: 2015
Coumarin and 7-hydroxy coumarins have great significance as natural fragrances, having a characteristic odour like vanilla beans and their hydroxy position at 7 has importance in biosynthesis. Treatment of 8-formyl-7-hydroxy coumarin with N,N-disubstituted cyano acetamides in the presence of piperidine afforded novel 8-substituted-7-hydroxy coumarin derivatives. Their structures were characterized by IR, 1H, 13C NMR, mass spectral and elemental analysis data. Two out of these 12 compounds, i.e. 2-Cyano-3-(7-hydroxy-2-oxo-2H-chromen-8-yl)-N-[2-(2-methoxy-phenoxy)-ethyl]-acrylamide and 2-Cyano-N-(2,5-dihydro-thiazol-2-yl)-3-(7-hydroxy-2-oxo-2H-chromen-8-yl)-acryl amide showed enhanced in vitro antifungal activity against Candida albicans and Aspergillus niger vis-à-vis standard, i.e. fluconazole, and enhanced in vitro antibacterial activity against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa vis-à-vis standard, i.e. norfloxacin. Graphical Abstract: [Figure not available: see fulltext.]. © 2013 The Author(s).