Insights into the binding of thiosemicarbazone derivatives with human serum albumin: spectroscopy and molecular modelling studies

Abstract

4-[(1Z)-1-(2-carbamothioylhydrazinylidene)ethyl]phenyl acetate [Ace semi],4-[(1Z)-1-(2-carbamothioylhydrazinylidene)ethyl]phenyl propanoate [Pro semi] from the family of thiosemicarbazones derivative has been newly synthesized. It has good anticancer activity as well as antibacterial and it is also less toxic in nature, its binding characteristics are therefore of huge interest for understanding pharmacokinetic mechanism of the drug. The binding of thiosemicarbazone derivative to human serum albumin (HSA) has been investigated by studying its quenching mechanism, binding kinetics and the molecular distance (r) between donor (HSA) and acceptor (thiosemicarbazone derivative) was estimated according to Forster’s theory of non-radiative energy transfer using fluorescence spectroscopy. The binding dynamics has been elaborated using synchronous fluorescence spectroscopy, and the feature of thiosemicarbazone derivative induced structural changes of HSA has been studied by circular dichorism, Fourier transform infrared spectroscopy. Molecular modelling simulations explore the hydrophobic interaction and hydrogen bonding which stabilizes the interaction.

Keywords:

• anticancer
• drug-binding pocket
• florescence resonance energy transfer
• molecular modelling

Acknowledgments

The authors are thankful to Centre for Research, Anna University, Chennai for offering Anna Centenary Fellowship (Lr. No. CRF/ACRF/ Jan. 2015/36) to Subramani Karthikeyan, Department of Medical Physics, Anna University, Chennai-25. We are also thankful for Mr Karuppusamy Shanmugam for helping in FTIR studies, Department of Physics, Anna University, Chennai-25, and also thankful to Dr N. Nishad Fathima for allowing us to utilize CD spectroscopy, CLRI, Adyar, Chennai-600 020.

Disclosure statement

No potential conflict of interest was reported by the authors.

Funding

This work was supported by the Board of Research in Nuclear Sciences, Department of Atomic Energy, Government of India [project number 2009/34/38/BRNS/3206].