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  2. Cytotoxicity and apoptotic activity of novel organobismuth(V) and organoantimony(V) complexes in different cancer cell lines

Cytotoxicity and apoptotic activity of novel organobismuth(V) and organoantimony(V) complexes in different cancer cell lines

  • Eur J Med Chem. 2016 Feb 15:109:254-67. doi: 10.1016/j.ejmech.2016.01.003.
Arshad Islam 1 Bernardo Lages Rodrigues 2 Ivana Marques Marzano 3 Elene C Perreira-Maia 4 Dalton Dittz 5 Miriam Teresa Paz Lopes 6 Muhammad Ishfaq 7 Frédéric Frézard 8 Cynthia Demicheli 9
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 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.
  • 4 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.
  • 5 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.
  • 6 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.
  • 7 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.
  • 8 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.
  • 9 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.
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.

Keywords

Apoptosis; Crystal structure; Cytotoxic activity; Flow cytometry; Organoantimony(V) dicarboxylates; Organobismuth(V) dicarboxylates.

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