title: Oxazolidinone derivatives: cytoxazone-linezolid hybrids induces apoptosis and senescence in DU145 prostate cancer cells.
abstract: In this study, we report the synthesis of novel oxazolidinone derivatives derived from linezolid 3 having p-methoxyphenyl group at C-4 position. In vitro evaluation for their anticancer activity toward cultured A549, DU145, HELA, and MCF7 were carried out. The series of compounds prepared displayed wide range of cytotoxicity in MTT assays (10-70 μM) across the cell lines tested. Of the all tested compounds 16 and 17 displayed good anticancer potential against A549 (lung) and DU145 (prostate) cancer cells. Further, to determine their anticancer potential, in the present study we have assessed effect of 17 on DU145 cells growth in in vitro assays. The results clearly demonstrated that the exposure of DU145 cells to 17 inhibits cell proliferation and induces apoptosis by activation of caspase-3 and -9. Long term exposure of DU145 cells to 17 induced cellular senescence confirmed by senescence marker β-galactosidase staining of cells on post exposure to 17. The results from this current report support that the oxazolidinone derivatives with ethyl and acryl substitutions showed promising anticancer activity which will be helpful to develop further novel anticancer agents with better therapeutic potential.
authors.affiliation: Organic and Biomolecular Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors.forename: Annavareddi
authors.initials: A
authors.lastname: Naresh
authors.affiliation: Organic and Biomolecular Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors.forename: Maddimsetti
authors.initials: M
authors.lastname: Venkateswara Rao
authors.affiliation: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors.forename: Sudha Sravanti
authors.initials: SS
authors.lastname: Kotapalli
authors.affiliation: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India. Electronic address: ummanni@iict.res.in.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Ummanni
authors.affiliation: Organic and Biomolecular Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India. Electronic address: venky@iict.res.in.
authors.forename: Batchu
authors.initials: B
authors.lastname: Venkateswara Rao
mesh_terms: D000081:Acetamides / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000187:drug effects*; D006801:Humans; D000069349:Linezolid; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010080:Oxazoles / Q000737:chemistry*; D023303:Oxazolidinones / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000473:pathology*
chemical_list: D000081:Acetamides; D000970:Antineoplastic Agents; D010080:Oxazoles; D023303:Oxazolidinones; C117832:cytoxazone; D053148:Caspase 3; D053453:Caspase 9; D000069349:Linezolid
keywords: Anticancer; Apoptosis; Cytoxazone; FEXZFZUCRSWTRS-PTLVDUHHSA-N; Linezolid; Oxazolidinones; Senescence