title: Preparation of novel antiproliferative emodin derivatives and studies on their cell cycle arrest, caspase dependent apoptosis and DNA binding interaction.
abstract: Emodin (1) is the major bioactive compound of several herb species, which belongs to anthraquinone class of compound. As a part of our drug discovery program, large quantities of emodin (1) was isolated from the roots of Rheum emodi and a library of novel emodin derivatives 2-15 were prepared to evaluate their antiproliferative activities against HepG2, MDA-MB-231 and NIH/3T3 cells lines. The derivatives 3 and 12 strongly inhibited the proliferation of HepG2 and MDA-MB-231 cancer cell line with an IC₅₀ of 5.6, 13.03 and 10.44, 5.027, respectively, which is comparable to marketed drug epirubicin (III). The compounds 3 and 12 were also capable of inducing cell cycle arrest and caspase dependent apoptosis in HepG2 cell lines and exhibit DNA intercalating activity. These emodin derivatives hold promise for developing safer alternatives to the marketed epirubicin.
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226001, UP, India. t_narendra@cdri.res.in
authors.forename: T
authors.initials: T
authors.lastname: Narender
authors.forename: P
authors.initials: P
authors.lastname: Sukanya
authors.forename: Komal
authors.initials: K
authors.lastname: Sharma
authors.forename: Surendar Reddy
authors.initials: SR
authors.lastname: Bathula
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000502:physiology*; D002417:Cattle; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D004642:Emodin / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D012250:Rheum / Q000737:chemistry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004268:DNA-Binding Proteins; D004247:DNA; C427203:calf thymus DNA; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D004642:Emodin
keywords: Anthraquinones; Anticancer agents; Apoptosis; Caspase-3; Cell cycle; Emodin derivatives; Rheum emodi