Synthesis and anti-inflammatory activity evaluation of novel triazolyl-isatin hybrids

摘要

Pramod K. Sharma ab , Sakshi Balwani c , Divya Mathur ad , Shashwat Malhotra a , Brajendra K. Singh a , Ashok K. Prasad a , Christophe Len ef , Erik V. Van der Eycken g , Balaram Ghosh c , Nigel G. J. Richards hi & Virinder S. Parmar aeh* a Department of Chemistry , Bioorganic Laboratory, University of Delhi , Delhi , India , b Chemical Research Laboratory, Wockhardt Research Centre , Aurangabad , Maharashtra , India , c Immunogenetics Laboratory, CSIR-Institute of Genomics and Integrative Biology , Delhi , India , d Department of Chemistry , Daulat Ram College, University of Delhi , Delhi , India , e Sorbonne Universités, Université de Technologie de Compiègne (UTC), Ecole Supérieure de Chimie Organique et Minérale (ESCOM) , Compiègne Cedex , France , f Department of Chemistry , University of Hull , Hull , UK , g Department of Chemistry , Laboratory for Organic & Microwave-Assisted Chemistry (LOMAC), University of Leuven (KU Leuven) , Leuven , Belgium , h Department of Chemistry and Chemical Biology , Indiana University-Purdue University (IUPUI) , Indianapolis , IN , USA , and i School of Chemistry, College of Physical Sciences & Engineering, Cardiff University , Cardiff , UK Address for correspondence: Prof. Virinder S. Parmar , Department of Chemistry , Bioorganic Laboratory, University of Delhi , Delhi – 110 007 , India . E-mail: virparmar@gmail.com New isatin-triazole based hybrids have been synthesized and evaluated for their inhibitory activity of TNF-α induced expression of Intercellular Adhesion Molecule-1 (ICAM-1) on the surface of human endothelial cells. Structure-activity relationship (SAR) studies revealed that the presence of the electron-attracting bromo substituent at position-5 of the isatin moiety played an important role in enhancing the anti-inflammatory potential of the synthesized compounds. Z-1-[3-(1H-1,2,4-Triazol-1-yl)propyl]-5-bromo-3-[2-(4-methoxyphenyl)hydrazono]indolin-2-one ( 19 ) with an IC₅₀?=?20?μM and 89% ICAM-1 inhibition with MTD at 200?μM was found to be the most potent of all the synthesized derivatives. Introduction of 1,2,4-triazole ring and electron-donating methoxy group on the phenylhydrazone moiety resulted in four-fold increase of the anti-inflammatory activity.