title: Insights into the strong in-vitro anticancer effects for bis(triphenylphosphane)iminium compounds having perchlorate, tetrafluoridoborate and bis(chlorido)argentate anions.
abstract: Three new compounds containing the bis(triphenylphosphane)iminium cation (PPN(+)) with ClO4(-), BF4(-) and [AgCl2](-) as counter anions have been synthesized and structurally characterized. The two derivatives with ClO4(-) and BF4(-) were found to be isostructural by single crystal X-ray diffraction. Interestingly, the three compounds show extremely potent antiproliferative effects against the human cancer cell line SKOV3. To gain insights into the possible mechanisms of biological action, several intracellular targets have been considered. Thus, DNA binding has been evaluated, as well as the effects of the compounds on the mitochondrial function. Furthermore, the compounds have been tested as possible inhibitors of the seleno-enzyme thioredoxin reductase.
authors.affiliation: Department of Biomedical Sciences, University of Padova, via Ugo Bassi 58/b, 35131 Padova, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Folda
authors.affiliation: Institute of Neuroscience (CNR), viale G. Colombo 3, 35131 Padova, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Scalcon
authors.affiliation: Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Kingdom of Saudi Arabia.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ghazzali
authors.affiliation: Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Kingdom of Saudi Arabia.
authors.forename: Mohammed H
authors.initials: MH
authors.lastname: Jaafar
authors.affiliation: Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Kingdom of Saudi Arabia.
authors.forename: Rais Ahmad
authors.initials: RA
authors.lastname: Khan
authors.affiliation: Department of Pharmacokinetics, Toxicology and Targeting, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
authors.forename: Angela
authors.initials: A
authors.lastname: Casini
authors.affiliation: Department of Biomedical Sciences, University of Padova, via Ugo Bassi 58/b, 35131 Padova, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Citta
authors.affiliation: Institute of Neuroscience (CNR), viale G. Colombo 3, 35131 Padova, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Bindoli
authors.affiliation: Department of Biomedical Sciences, University of Padova, via Ugo Bassi 58/b, 35131 Padova, Italy. Electronic address: mariapia.rigobello@unipd.it.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Rigobello
authors.affiliation: Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Kingdom of Saudi Arabia.
authors.forename: Khalid
authors.initials: K
authors.lastname: Al-Farhan
authors.affiliation: Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Kingdom of Saudi Arabia.
authors.forename: Ali
authors.initials: A
authors.lastname: Alsalme
authors.affiliation: Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Kingdom of Saudi Arabia; Leiden Institute of Chemistry, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands. Electronic address: reedijk@chem.leidenuniv.nl.
authors.forename: Jan
authors.initials: J
authors.lastname: Reedijk
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008928:Mitochondria / Q000187:drug effects; D008969:Molecular Sequence Data; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D018030:Silver Compounds / Q000737:chemistry*; D013880:Thioredoxin-Disulfide Reductase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D009942:Organometallic Compounds; D018030:Silver Compounds; D004247:DNA; D013880:Thioredoxin-Disulfide Reductase
keywords: Anti-cancer compounds; Crystal structure; DNA binding; Isomorphism; Mitochondria; Thioredoxin reductase