title: Synthesis and biological evaluation of nitric oxide-donating analogues of sulindac for prostate cancer treatment.
abstract: A series of analogues of the non-steroidal anti-inflammatory drug (NSAID) sulindac 1 were synthesised tethered to nitric oxide (NO) donating functional groups. Sulindac shows antiproliterative effects against immortal PC3 cell lines. It was previously demonstrated that the effect can be enhanced when tethered to NO releasing groups such as nitrate esters, furoxans and sydnonimines. To explore this approach further, a total of fifty-six sulindac-NO analogues were prepared and they were evaluated as NO-releasing cytotoxic agents against prostate cancer (PCa) cell lines. Compounds 1k and 1n exhibited significant cytotoxic with IC50 values of 6.1±4.1 and 12.1±3.2μM, respectively, coupled with observed nitric oxide release.
authors.affiliation: EaStCHEM School of Chemistry, Biomolecular Sciences Research Complex, University of St Andrews, North Haugh, St Andrews, Fife KY16 9ST, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Nortcliffe
authors.affiliation: EaStCHEM School of Chemistry, Biomolecular Sciences Research Complex, University of St Andrews, North Haugh, St Andrews, Fife KY16 9ST, UK.
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Ekstrom
authors.affiliation: Tissue Injury and Repair Group, Department of Clinical and Surgical Sciences (Surgery), University of Edinburgh, Edinburgh EH16 4SB, UK.
authors.forename: James R
authors.initials: JR
authors.lastname: Black
authors.affiliation: Tissue Injury and Repair Group, Department of Clinical and Surgical Sciences (Surgery), University of Edinburgh, Edinburgh EH16 4SB, UK.
authors.forename: James A
authors.initials: JA
authors.lastname: Ross
authors.affiliation: Prostate Research Group, Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh EH4 2XR, UK.
authors.forename: Fouad K
authors.initials: FK
authors.lastname: Habib
authors.affiliation: EaStCHEM School of Chemistry, Biomolecular Sciences Research Complex, University of St Andrews, North Haugh, St Andrews, Fife KY16 9ST, UK.
authors.forename: Nigel P
authors.initials: NP
authors.lastname: Botting
authors.affiliation: EaStCHEM School of Chemistry, Biomolecular Sciences Research Complex, University of St Andrews, North Haugh, St Andrews, Fife KY16 9ST, UK. Electronic address: do1@st-andrews.ac.uk.
authors.forename: David
authors.initials: D
authors.lastname: O'Hagan
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008297:Male; D015394:Molecular Structure; D009569:Nitric Oxide / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013329:Structure-Activity Relationship; D013467:Sulindac / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D013467:Sulindac; D009569:Nitric Oxide
keywords: Furoxan; Nitric oxide; Prostate cancer; Sulindac analogues; Sydnonimine