title: Synthesis and anticancer potential of novel xanthone derivatives with 3,6-substituted chains.
abstract: In an effort to develop new drug candidates with enhanced anticancer activity, our team synthesized and assessed the cytotoxicity of a series of novel xanthone derivatives with two longer 3,6-disubstituted amine carbonyl methoxy side chains on either benzene ring in selected human cancer cell lines. An MTT assay revealed that a set of compounds with lower IC50 values than the positive control, 5-FU, exhibited greater anticancer effects. The most potent derivative (XD8) exhibited anticancer activity in MDA-MB-231, PC-3, A549, AsPC-1, and HCT116 cells lines with IC50 values of 8.06, 6.18, 4.59, 4.76, and 6.09μM, respectively. Cell cycle analysis and apoptosis activation suggested that the mechanism of action of these derivatives includes cell cycle regulation and apoptosis induction.
authors.affiliation: Department of Radiation Oncology, University of Florida, Cancer/Genetics Research Complex, 2033 Mowry Road, Suite 145, PO Box 103633, Gainesville, FL 32610, USA. Electronic address: liucha@shands.ufl.edu.
authors.forename: Chaomei
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, University of Florida, Cancer/Genetics Research Complex, 2033 Mowry Road, Suite 145, PO Box 103633, Gainesville, FL 32610, USA.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, University of Florida, Cancer/Genetics Research Complex, 2033 Mowry Road, Suite 145, PO Box 103633, Gainesville, FL 32610, USA.
authors.forename: Zhenhuan
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, University of Florida, Cancer/Genetics Research Complex, 2033 Mowry Road, Suite 145, PO Box 103633, Gainesville, FL 32610, USA.
authors.forename: Steven B
authors.initials: SB
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, University of Florida, Cancer/Genetics Research Complex, 2033 Mowry Road, Suite 145, PO Box 103633, Gainesville, FL 32610, USA.
authors.forename: Shanmin
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Radiation Oncology, University of Florida, Cancer/Genetics Research Complex, 2033 Mowry Road, Suite 145, PO Box 103633, Gainesville, FL 32610, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, University of Florida, Cancer/Genetics Research Complex, 2033 Mowry Road, Suite 145, PO Box 103633, Gainesville, FL 32610, USA.
authors.forename: Liangjie
authors.initials: L
authors.lastname: Yin
authors.affiliation: Department of Radiation Oncology, University of Florida, Cancer/Genetics Research Complex, 2033 Mowry Road, Suite 145, PO Box 103633, Gainesville, FL 32610, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Swarts
authors.affiliation: Department of Radiation Oncology, University of Florida, Cancer/Genetics Research Complex, 2033 Mowry Road, Suite 145, PO Box 103633, Gainesville, FL 32610, USA.
authors.forename: Sadasivan
authors.initials: S
authors.lastname: Vidyasagar
authors.affiliation: Department of Radiation Oncology, University of Florida, Cancer/Genetics Research Complex, 2033 Mowry Road, Suite 145, PO Box 103633, Gainesville, FL 32610, USA.
authors.forename: Lurong
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, University of Florida, Cancer/Genetics Research Complex, 2033 Mowry Road, Suite 145, PO Box 103633, Gainesville, FL 32610, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Okunieff
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D013329:Structure-Activity Relationship; D044004:Xanthones / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D044004:Xanthones; C505407:CASP3 protein, human; C505520:CASP7 protein, human; D053148:Caspase 3; D053179:Caspase 7
keywords: 3,6-Substituted long chains; A549; Anticancer potential; Apoptosis; Caspase 3/7 activity; Cell cycle arrest; IC(50); Structure–activity relationship; Synthesis; Xanthone derivatives