Synthesis, Structure–Activity Relationship of Some New Triorganotin(IV) Derivatives of Dipeptides as Anti-Inflammatory Agents

Abstract

New triorganotin(IV) derivatives of dipeptides with general formulae, R₃Sn(HL), where R = Me and Ph, and HL is the monoanion of histidinylalanine and histidinylleucine, have been synthesized and characterized on the basis of infrared (IR), multinuclear NMR (¹H, ¹³C, and ¹¹⁹Sn), and ¹¹⁹Sn Mössbauer spectroscopic studies. These derivatives exhibit distorted trigonal-bipyramidal geometry around tin in which dipeptide anion acts as bidentate ligand coordinating through carboxyl oxygen and amino nitrogen. Ph₃Sn(HHis-Ala),

Ph₃Sn(HHis-Leu), and previously reported Ph₂Sn(His-Ala), Me₂Sn(His-Ala), n-Oct₂Sn(His-Ala), Me₂Sn(His-Leu), n-Oct₂Sn(His-Leu), Ph₃Sn(HTyr-Phe), Ph₂Sn(Tyr-Phe), Bu₂Sn-(Tyr-Phe), and n-Oct₂Sn(Tyr-Phe) along with standard drugs, viz. phenyl butazone and indomethacin were screened for in vivo anti-inflammatory activity and acute toxicity (LD₅₀). Diorganotin(IV) derivatives are more active than triorganotin(IV) derivatives. Me₂Sn(His-Leu) shows the highest activity.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.

GRAPHICAL ABSTRACT

Keywords:

• Organotin(IV) complexes
• dipeptide
• NMR spectroscopy
• ¹¹⁹Sn Mössbauer spectroscopy
• anti-inflammatory activity

Acknowledgments

M.N. is thankful to the Department of Science and Technology (DST) for the financial support as this work is a part of major research project (grant no. SP/S1/F-07/2000) sponsored by the DST, New Delhi, India. H.S. is also grateful to DST (India) for the Research Fellowship. Financial support for the Mössbauer work from the National Institute of Biomedical Research Support Program (MBRS/SCORE, GM 08005) is gratefully acknowledged. Authors are highly thankful to (Late) Dr. Ashok Kumar, Department of Pharmacology, LLRM Medical College, Meerut, India, for providing the results of toxicity and anti-inflammatory activity.

The first and second authors contributed equally. The third and fourth authors recorded ¹¹⁹Sn Mössbauer spectra.