title: Microwave-assisted synthesis, characterization and cytotoxic studies of novel estrogen receptor α ligands towards human breast cancer cells.
abstract: A new, simple, and microwave-assisted, solution-phase T3P®-DMSO mediated method for the preparation of a novel class of estrogen receptor alpha (ERα) ligands based on the 2-phenylquinoline scaffold was developed. Furthermore, the novel ERα ligands were tested for their bioactivity against ERα-positive and ERα-negative cell lines. The ligand (entry 4), with amine and nitro group substitution at C4 position, displayed significant cytotoxicity against MCF-7 and HepG2 cells with an IC50 value of 6 and 11μM, respectively. On the other hand, ERα-negative cells displayed resistance to quinolines induced cytotoxicity with an IC50 value >100Mm and they does not induce cytotoxicity in normal breast epithelial cells. Molecular docking analyses suggest a consistent binding mode for these ERα ligands in the ligand binding domain of the human ERα and predict the ligands to occupy the hydrophobic cavity in a similar fashion as estradiol or GW2368.
authors: Laboratory of Chemical Biology, Department of Chemistry, Bangalore University, Palace Road, Bangalore 560 001, India.
authors: Hanumantharayappa
authors: H
authors: Bharathkumar
authors: Department of Chemistry, University of Mysore, Mysore 570 006, India.
authors: Chakrabhavi Dhananjaya
authors: CD
authors: Mohan
authors: Department of Chemistry, University of Mysore, Mysore 570 006, India.
authors: Hanumappa
authors: H
authors: Ananda
authors: Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, CB2 1EW Cambridge, United Kingdom.
authors: Julian E
authors: JE
authors: Fuchs
authors: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117 597, Singapore.
authors: Feng
authors: F
authors: Li
authors: Frontier Research Center for Post-genome Science and Technology Hokkaido University, Sapporo 060 0808, Japan.
authors: Shobith
authors: S
authors: Rangappa
authors: CAS in Crystallography and Biophysics, University of Madras, Chennai 600 025, Tamil Nadu, India.
authors: Mohan
authors: M
authors: Surender
authors: Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, CB2 1EW Cambridge, United Kingdom.
authors: Krishna C
authors: KC
authors: Bulusu
authors: Department of Studies and Research in Biochemistry, Tumkur University, Tumkur 572 103, India.
authors: Kesturu S
authors: KS
authors: Girish
authors: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117 597, Singapore.
authors: Gautam
authors: G
authors: Sethi
authors: Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, CB2 1EW Cambridge, United Kingdom.
authors: Andreas
authors: A
authors: Bender
authors: Laboratory of Chemical Biology, Department of Chemistry, Bangalore University, Palace Road, Bangalore 560 001, India.
authors: Basappa
authors: Department of Chemistry, University of Mysore, Mysore 570 006, India.
authors: Kanchugarakoppal S
authors: KS
authors: Rangappa
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D047628:Estrogen Receptor alpha / Q000737:chemistry* / Q000378:metabolism; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D008024:Ligands; D061986:MCF-7 Cells; D008872:Microwaves; D062105:Molecular Docking Simulation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D008024:Ligands; D011804:Quinolines; C037219:quinoline
keywords: Cancer; Estrogen receptor ligand; Molecular docking; Quinolines; T3P-DMSO mediated synthesis