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Zinc complex of tryptophan appended 1,4,7,10-tetraazacyclododecane as potential anticancer agent: Synthesis and evaluation.
Adhikari, Anupriya; Kumari, Neelam; Adhikari, Manish; Kumar, Nitin; Tiwari, Anjani K; Shukla, Abha; Mishra, Anil K; Datta, Anupama.
Afiliação
  • Adhikari A; Institute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organization, Brig S K Mazumdar Road, Delhi, India; Department of Chemistry, Kanya Gurukul Campus, GKV, Haridwar, Uttarakhand, India.
  • Kumari N; Institute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organization, Brig S K Mazumdar Road, Delhi, India.
  • Adhikari M; Institute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organization, Brig S K Mazumdar Road, Delhi, India.
  • Kumar N; Institute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organization, Brig S K Mazumdar Road, Delhi, India.
  • Tiwari AK; Institute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organization, Brig S K Mazumdar Road, Delhi, India.
  • Shukla A; Department of Chemistry, Kanya Gurukul Campus, GKV, Haridwar, Uttarakhand, India.
  • Mishra AK; Institute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organization, Brig S K Mazumdar Road, Delhi, India. Electronic address: akmishra63@gmail.com.
  • Datta A; Institute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organization, Brig S K Mazumdar Road, Delhi, India. Electronic address: anupama@inmas.drdo.in.
Bioorg Med Chem ; 25(13): 3483-3490, 2017 07 01.
Article em En | MEDLINE | ID: mdl-28495383
ABSTRACT
With the rising incidences of cancer cases, the quest for new metal based anticancer drugs has led to extensive research in cancer biology. Zinc complexes of amino acid residue side chains are well recognized for hydrolysis of phosphodiester bond in DNA at faster rate. In the presented work, a Zn(II) complex of cyclen substituted with two l-tryptophan units, Zn(II)-Cyclen-(Trp)2 has been synthesized and evaluated for antiproliferative activity. Zn(II)-Cyclen-(Trp)2 was synthesized in ∼70% yield and its DNA binding potential was evaluated through QM/MM study which suggested good binding (G=-9.426) with B-DNA. The decrease in intensity of the positive and negative bands of CT-DNA at 278nm and 240nm, respectively demonstrated an effective unwinding of the DNA helix with loss of helicity. The complex was identified as an antiproliferative agent against U-87MG cells with 5 fold increase in apoptosis with respect to control (2h post incubation, IC50 25µM). Electrophoresis and comet assay studies exhibited an increase in DNA breakage after treatment with complex while caspase-3/ß-actin cleavage established a caspase-3 dependent apoptosis pathway in U-87 MG cells after triggering DNA damage. In vivo tumor specificity of the developed ligand was validated after radiocomplexation with 99mTc (>98% radiochemical yield and specific activity of 2.56GBq/µmol). Avid tumor/muscle ratio of >6 was depicted in biodistribution and SPECT imaging studies in U-87 MG xenograft model nude mice.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Compostos Organometálicos / Triptofano / Zinco / Compostos Heterocíclicos / Antineoplásicos Limite: Animals / Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Compostos Organometálicos / Triptofano / Zinco / Compostos Heterocíclicos / Antineoplásicos Limite: Animals / Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article