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Dibutyltin(IV) complexes containing arylazobenzoate ligands: chemistry, in vitro cytotoxic effects on human tumor cell lines and mode of interaction with some enzymes

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Summary

Dibutyltin(IV) complexes of composition Bu2Sn(LH)2, where LH is a carboxylate residue derived from 2-[(E)-(5-tert-butyl-2-hydroxyphenyl)diazenyl]benzoate (L1H) with water molecule (1), 4-[(E)-(5-tert-butyl-2-hydroxyphenyl)diazenyl]benzoate (L2H) (2) and 4-[(E)-(4-hydroxy-5-methylphenyl)diazenyl]benzoate (L3H) (3), were synthesized and characterized by spectroscopic (1H, 13C and 119Sn NMR, IR, 119Sn Mössbauer) techniques. A full characterization was accomplished from the crystal structure of complex 1. The molecular structures and geometries of the complexes (1a i.e. 1 without water molecule and 3) were fully optimized using the quantum mechanical method (PM6). Complexes 1 and 3 were found to exhibit stronger cytotoxic activity in vitro across a panel of human tumor cell lines viz., A498, EVSA-T, H226, IGROV, M19 MEL, MCF-7 and WIDR. Compound 3 is found to be four times superior for the A498, EVSA-T and MCF-7 cell lines than CCDP (cisplatin), and four, eight and sixteen times superior for the A498, H226 and MCF-7 cell lines, respectively, compared to ETO (etoposide). The mechanistic role of cytotoxic activity of test compounds is discussed in relation to the theoretical results of docking studies with some key enzymes such as ribonucleotide reductase, thymidylate synthase, thymidylate phosphorylase and topoisomerase II associated with the propagation of cancer.

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Acknowledgements

The financial support of the Department of Science & Technology, New Delhi, India (Grant No.SR/S1/IC-03/2005,TSBB and SR/S1/OC-11A/2006, PS), of the Università degli Studi di Palermo, Italy (Grants ORPA079E5M and ORPA0737W2) and the University Grants Commission, New Delhi, India through SAP-DSA, Phase-III, are gratefully acknowledged. The in vitro cytotoxicity experiments were carried out by Ms. P. F. van Cuijk in the Laboratory of Translational Pharmacology, Department of Medical Oncology, Erasmus Medical Center, Rotterdam, The Netherlands, under the supervision of Dr. E. A. C. Wiemer and Prof. Dr. G. Stoter.

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Authors and Affiliations

  1. Department of Chemistry, North-Eastern Hill University, NEHU Permanent Campus, Umshing, Shillong, 793 022, India

    Tushar S. Basu Baul & Anup Paul

  2. Dipartimento di Chimica Inorganica e Analitica, “Stanislao Cannizzaro”, Università degli Studi di Palermo, Viale delle Scienze, Parco D’Orleans II, Edificio 17, 90128, Palermo, Italy

    Lorenzo Pellerito & Michelangelo Scopelliti

  3. Department of Chemistry, Guru Nanak Dev University, Amritsar, 143005, India

    Palwinder Singh & Pooja Verma

  4. School of Life & Environmental Science, Deakin University, Geelong, Victoria, 3217, Australia

    Andrew Duthie

  5. Pharmachemie BV, PO Box 552, 2003 RN, Haarlem, The Netherlands

    Dick de Vos

  6. Department of Chemistry, University of Malaya, 50603, Kuala Lumpur, Malaysia

    Edward R. T. Tiekink

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  1. Tushar S. Basu Baul
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Fig. S1

Unit cell contents viewed in projection down the c-axis for 1 (GIF 138 kb)

High resolution image (TIFF 383 kb)

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Basu Baul, T.S., Paul, A., Pellerito, L. et al. Dibutyltin(IV) complexes containing arylazobenzoate ligands: chemistry, in vitro cytotoxic effects on human tumor cell lines and mode of interaction with some enzymes. Invest New Drugs 29, 285–299 (2011). https://doi.org/10.1007/s10637-009-9360-3

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