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

被引:71
作者
Islam, Arshad [1 ,2 ]
Rodrigues, Bernardo Lages [2 ]
Marzano, Ivana Marques [2 ]
Perreira-Maia, Elene C. [2 ]
Dittz, Dalton [3 ]
Paz Lopes, Miriam Teresa [3 ]
Ishfaq, Muhammad [4 ,5 ]
Frezard, Frederic [1 ]
Demicheli, Cynthia [2 ]
机构
[1] Fed Univ Minas Gerais UFMG, Inst Biol Sci, Dept Physiol & Biophys, Av Antonio Carlos 6627, BR-31270901 Belo Horizonte, MG, Brazil
[2] Fed Univ Minas Gerais UFMG, Inst Exact Sci, Dept Chem, Av Antonio Carlos 6627, BR-31270901 Belo Horizonte, MG, Brazil
[3] Fed Univ Minas Gerais UFMG, Inst Biol Sci, Dept Pharmacol, Antonio Carlos 6627, BR-31270901 Belo Horizonte, MG, Brazil
[4] Univ Southampton, Fac Med, Canc Res UK Ctr, Southampton SO9 5NH, Hants, England
[5] Shaukat Khanum Mem Canc Hosp & Res Ctr, Lahore, Punjab, Pakistan
关键词
Organobismuth(V) dicarboxylates; Organoantimony(V) dicarboxylates; Crystal structure; Cytotoxic activity; Apoptosis; Flow cytometry; RING-CHAIN TAUTOMERISM; IN-VITRO; CRYSTAL-STRUCTURES; FLOW-CYTOMETRY; DIPHENYLANTIMONY(III) DERIVATIVES; BIOLOGICAL CHARACTERIZATION; ANTILEISHMANIAL ACTIVITY; 2-AROYL-BENZOIC ACIDS; BINDING-PROPERTIES; ANTITUMOR-ACTIVITY;
D O I
10.1016/j.ejmech.2016.01.003
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
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. (C) 2016 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码:254 / 267
页数:14
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