Computational evaluation and experimental in vitro antibacterial, antifungal and antiviral activity of bis-Schiff bases of isatin and its derivatives

Abstract

A computational model has been developed for the rational design of bioactive pharmacophore sites as an antibacterial, antifungal and antiviral candidates based on available X-ray structures of bis-Schiff bases (Blagus et al., Maced J Chem Chem Eng 29:117-138, 2010; Nabei et al., Polyhedron 28:1734-1739, 2009; Zhang et al., Inorg Chem Commun 14:1636-1639, 2011; Zhong et al., Eur J Med Chem 41:1090-1092, 2006; Zhou et al., Inorg Chim Acta 359:1442-1448, 2006). A dozen of bis-Schiff bases 3-14 of isatin, benzylisatin and 5-fluoroisatin 1a-c were designed using this model. The compounds were screened for antibacterial, antifugal and antiviral activity against a panel of DNA and RNA viruses. The most potent of these compounds 8 and 11 was tested in viral cultures for their ability to present a potential (Oδ-- Nδ-) antiviral pharmacophore site. Compounds 8 and 11 were the most cytotoxic in HEL cells. All these synthesized bis-Schiff bases were also tested for their antibacterial and antifungal activities. They did not display activity against S. cerevisiae (ATCC 28383) or C. albicans (CIP 1180-79); may be because they did not have an antibacterial pharmacophore site (X δ--Yδ+). The best inhibitors tested in vitro against HIV-1 are genetically predisposed to be inhibited by similar pharmacophore sites. The results from all the aspects of this bioinformatic approaches are discussed as par with our experience with screening candidates. Graphical Abstract: [Figure not available: see fulltext.] © 2012 Springer Science+Business Media, LLC.