title: Cytotoxicity and apoptotic activity of novel organobismuth(V) and organoantimony(V) complexes in different cancer cell lines.
abstract: Novel organobismuth(V) and organoantimony(V) complexes of Ph3ML2 type were synthesized, in which L = deprotonated 2-acetylbenzoic acid (2AcBH), 4-acetylbenzoic acid (4AcBH) or 5-acetylsalicylic acid (5AcSH) and M = bismuth(V) or antimony(V). Complexes [Ph3Bi(2AcB)2] (1) [Ph3Sb(4AcB)2] (2), [Ph3Bi(4AcB)2] (3) and [Ph3Sb(5AcS)2(.)CHCl3] (4) were characterized by elemental analysis, IR, and NMR. Crystal structures of 2 and 4 were determined by single crystal X-ray diffraction. In vitro cytotoxic activities against cancerous (human chronic myelogenous leukemia, K562 and murine metastatic melanoma, B16F10) and healthy non-cancerous (murine fibroblasts, L929 and murine melanocytes, Melan-A) cells showed that, compared to free ligands, both of the metal complexes are more active as anticancer agents at low concentration in cancerous cell lines, but also possessed toxic effect at comparatively higher concentration towards the non-cancerous cells. The organobismuth(V) complex Ph3Bi(2AcB)2 was found to be more active than the Ph3BiCl2 metal precursor against the tumor cell lines and exhibited the highest selectivity index. Moreover, evaluation of the pro-apoptotic activity of Ph3Bi(2AcB)2 in B16F10 cells, by quantifying the cellular DNA using flow cytometry, indicates that cell cycle arrest and cell apoptosis contribute to the drug cytotoxicity. This work supports the great potential of organobismuth(V) dicarboxylate complexes as anticancer agents.
authors.affiliation: Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Av. Antônio Carlos 6627, 31270-901, Belo Horizonte, MG, Brazil; Department of Chemistry, Institute of Exact Sciences, Federal University of Minas Gerais (UFMG), Av. Antônio Carlos 6627, 31270-901, Belo Horizonte, MG, Brazil. Electronic address: arshad.cgl@gmail.com.
authors.forename: Arshad
authors.initials: A
authors.lastname: Islam
authors.affiliation: Department of Chemistry, Institute of Exact Sciences, Federal University of Minas Gerais (UFMG), Av. Antônio Carlos 6627, 31270-901, Belo Horizonte, MG, Brazil. Electronic address: bernardo@mail.qui.ufmg.br.
authors.forename: Bernardo Lages
authors.initials: BL
authors.lastname: Rodrigues
authors.affiliation: Department of Chemistry, Institute of Exact Sciences, Federal University of Minas Gerais (UFMG), Av. Antônio Carlos 6627, 31270-901, Belo Horizonte, MG, Brazil. Electronic address: ivanadq@gmail.com.
authors.forename: Ivana Marques
authors.initials: IM
authors.lastname: Marzano
authors.affiliation: Department of Chemistry, Institute of Exact Sciences, Federal University of Minas Gerais (UFMG), Av. Antônio Carlos 6627, 31270-901, Belo Horizonte, MG, Brazil. Electronic address: elene@qui.ufmg.br.
authors.forename: Elene C
authors.initials: EC
authors.lastname: Perreira-Maia
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Av. Antônio Carlos 6627, 31270-901, Belo Horizonte, MG, Brazil. Electronic address: daltondittz@gmail.com.
authors.forename: Dalton
authors.initials: D
authors.lastname: Dittz
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Av. Antônio Carlos 6627, 31270-901, Belo Horizonte, MG, Brazil. Electronic address: mtpl@icb.ufmg.br.
authors.forename: Miriam Teresa
authors.initials: MT
authors.lastname: Paz Lopes
authors.affiliation: Cancer Research UK Centre, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; Shaukat Khanum Memorial Cancer Hospital and Research Centre, 7A/Bl-R3, Johar Town, Lahore, Punjab, Pakistan. Electronic address: M.ishfaq@southampton.ac.uk.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ishfaq
authors.affiliation: Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Av. Antônio Carlos 6627, 31270-901, Belo Horizonte, MG, Brazil. Electronic address: frezard@icb.ufmg.br.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Frézard
authors.affiliation: Department of Chemistry, Institute of Exact Sciences, Federal University of Minas Gerais (UFMG), Av. Antônio Carlos 6627, 31270-901, Belo Horizonte, MG, Brazil. Electronic address: cynthia.demicheli@pq.cnpq.br.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Demicheli
mesh_terms: D000818:Animals; D000965:Antimony / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001729:Bismuth / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D000965:Antimony; D001729:Bismuth
keywords: Apoptosis; Crystal structure; Cytotoxic activity; Flow cytometry; Organoantimony(V) dicarboxylates; Organobismuth(V) dicarboxylates