title: Sulfonated Schiff base Sn(IV) complexes as potential anticancer agents.
abstract: Syntheses, crystal structures and biological activities of the diphenoxo-bridged diorgano dinuclear Sn(IV) compounds [Sn(Et)2(HL)(H2O)]2(1) and [Sn(n-Bu)2(HL)(H2O)]2(2) derived from the Schiff base 2-[(2,3-dihydroxyphenyl)methylideneamino]benzenesulfonic acid trihydrate (H3L·3H2O) are described. The monoprotonated form (HL2-) of the Schiff base behaves as O,O'-bidentate ligand, chelating the metal by the two phenoxo oxygen atoms. The hexacoordinated metal centres in 1 and 2 are bridged by a phenoxo oxygen and the remaining coordination positions are fulfilled by the other phenoxo oxygen, two organic groups (ethyl for 1 and n-butyl for 2) and a water molecule. A two dimensional zigzag sheet in 1 and three dimensional polymeric networks in H3L·3H2O and 2 are stabilized by a number of non-covalent, H-bonding and π⋯π stacking interactions. The DNA binding activities of these complexes have been studied by UV-vis and fluorescence spectroscopies. Their antiproliferative efficacies have been evaluated on A-549, HeLa and MDA-MB-231 cancer cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. IC50values (1.35±0.23, 2.43±0.54 and 1.74±0.04μM for 2) are indicative of a substantial cytotoxicity of 2, mainly towards the A-549 lung cancer cell line. The greater antiproliferative efficacy of 2has further been studied by fluorescence activated cell sorting (FACS) and nuclear morphology by Hoechst/propidium iodide (PI) double staining method. The possible mode of the apoptotic pathway for 2has been substantiated by the reactive oxygen species (ROS) generation studies.
authors.affiliation: Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisbon, Portugal. Electronic address: h.susanta@gmail.com.
authors.forename: Susanta
authors.initials: S
authors.lastname: Hazra
authors.affiliation: Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisbon, Portugal.
authors.forename: Anup
authors.initials: A
authors.lastname: Paul
authors.affiliation: Department of Zoology, Faculty of Science, Banaras Hindu University, Varanasi 221 005, India.
authors.forename: Gunjan
authors.initials: G
authors.lastname: Sharma
authors.affiliation: Department of Zoology, Faculty of Science, Banaras Hindu University, Varanasi 221 005, India. Electronic address: kochbiplob@gmail.com.
authors.forename: Biplob
authors.initials: B
authors.lastname: Koch
authors.affiliation: Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisbon, Portugal. Electronic address: fatima.guedes@tecnico.ulisboa.pt.
authors.forename: M Fátima C Guedes
authors.initials: MFCG
authors.lastname: da Silva
authors.affiliation: Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisbon, Portugal.
authors.forename: Armando J L
authors.initials: AJL
authors.lastname: Pombeiro
mesh_terms: D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001557:Benzenesulfonates / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000494:pharmacology; D004247:DNA / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008968:Molecular Conformation; D009947:Organotin Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000819:agonists / Q000378:metabolism; D012545:Schiff Bases / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014001:Tin / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D056831:Coordination Complexes; D009947:Organotin Compounds; D017382:Reactive Oxygen Species; D012545:Schiff Bases; D014001:Tin; D004247:DNA; C427203:calf thymus DNA
keywords: Cytotoxicity in vitro; DNA binding; Diorgano dinuclear Sn(IV); Reactive oxygen species; Sulfonated Schiff base