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Triphenyltin(IV) 2-[(E)-2-(aryl)-1-diazenyl]benzoates as anticancer drugs: synthesis, structural characterization, in vitro cytotoxicity and study of its influence towards the mechanistic role of some key enzymes

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Summary

Triphenyltin(IV) complexes of composition [Ph3SnL1H]n (1) and [Ph3SnL2H]n (2) (where L1H = 2-[(E)-2-(3-formyl-4-hydroxyphenyl)-1-diazenyl]benzoate and L2H = 2-[(E)-2-(4-Hydroxy-5-methylphenyl)-1-diazenyl]benzoate) were synthesized and characterized by spectroscopic (1H, 13C and 119Sn NMR, IR, 119Sn Mössbauer) techniques in combination with elemental analysis. The molecular structures and geometries of the complexes (1 and 2) were fully optimized using the quantum mechanical method (PM3). Complexes (1 and 2) were found to exhibit stronger cytotoxic activity in vitro across a panel of human tumour cell lines viz., A498, EVSA-T, H226, IGROV, M19 MEL, MCF-7 and WIDR. The test compounds 1 and 2 exhibit comparable results and both the compounds are found to be far superior to CCDP (cisplatin), 5-FU (5-fluorouracil) and ETO (etoposide) across a panel of cell lines and the activity is more pronounced for the A498 (22 fold) and H226 (33 fold) cell lines compared to CCDP, and A498 (13 fold), H226 (39 fold) and MCF-7 (33 fold) cell lines compared to ETO. The test compounds are even 23 fold more active in magnitude in terms of the ID50 value at least against the H226 cell lines when compared with MTX (methotrexate). Further, the mechanistic role of cytotoxic activity of test compounds (1 and 2), are discussed in relations to the theoretical results of docking studies with some of the key enzymes such as ribonucleotide reductase, thymidylate synthase, thymidylate phosphorylase and topoisomerase II.

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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. Pharmachemie BV, P.O. Box 552, 2003, RN Haarlem, The Netherlands

    Dick de Vos

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  1. Tushar S. Basu Baul
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Correspondence to Tushar S. Basu Baul.

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Tushar S. Basu Baul dedicates this paper to his collaborator Dr. D. de Vos on his retirement, who was a key person in his research career.

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Basu Baul, T.S., Paul, A., Pellerito, L. et al. Triphenyltin(IV) 2-[(E)-2-(aryl)-1-diazenyl]benzoates as anticancer drugs: synthesis, structural characterization, in vitro cytotoxicity and study of its influence towards the mechanistic role of some key enzymes. Invest New Drugs 28, 587–599 (2010). https://doi.org/10.1007/s10637-009-9293-x

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