One-pot synthesis via 1, 3-dipolar cycloaddition reaction to piperazinyl-quinolinyl dispiro heterocyclic derivatives and spectrofluorometric and molecular docking studies on their binding with human serum albumin Arul Murugesan a , Robert Moonsamy Gengan a, * , Ramar Rajamanikandan b , Malaichamy Ilanchelian b a Department of Chemistry, Faculty of Applied Sciences, Durban University of Technology, Durban, South Africa b Department of Chemistry, Bharathiar University Coimbatore, India article info Article history: Received 4 February 2017 Received in revised form 4 August 2017 Accepted 5 August 2017 Available online 7 August 2017 Keywords: 1, 3 Dipolar cycloaddition Microwave irradiation HSA protein Molecular docking abstract A series of novel dispiro piperazinyl-quinolinyl-thioxothiazolidin-2, 4-dione derivatives were synthesised and characterised by FT-IR 1 H, 13 C, 2D NMR and HRMS spectroscopic techniques. A representative compound 1'-(2-(4-methylpiperazin-1-yl)quinolin-3-yl)-2 00 -thioxo-5 0 ,6 0 ,7 0 ,7a'-tetrahydro-1 0 H,2H-dispiro [acenaphthylene-1,3 0 -pyrrolizine-2 0 ,5 00 -thiazolidine]-2,4 00 -dione was studied for its binding ability with human serum albumin (HSA) using the fluorescence quench titration method. Addition of the compound to HSA produced slight fluorescence quenching and red shift. The free energy change for the complex- ation process was evaluated as 29.98 kJ mol 1 thereby indicating a spontaneous and highly favourable reaction. Molecular docking analyses revealed the binding as 20.79 kJ mol 1 which was analogous with the experimental value obtained from emission data. It was concluded that TYR-263 is the moiety responsible for the binding in the complex. © 2017 Elsevier B.V. All rights reserved. 1. Introduction Rhodanine based molecules display good biological activities including anti-inflammatory and anti-hypertensive activities [1] hence they are highly utilised in drug discovery strategies [2]. The pyrrolo-thiazoles are also endowed with a wide-ranging of bio- logical activities, namely for their heptoprotective [3], anti-biotic [4], anti-diabetic [5] and anti-convulsant actions [6]. The 2, 3 dihydro-4-quinolone derivatives, present in many alkaloids [7], is an important intermediate in organic synthesis [8] and exhibits a wide range of pharmacological properties such as anti-bacterial [9], anti-malarial [10], anti-tumor [11], CRTH2 antagonist receptor [12] and 5HT6 serotonin receptor [13]. When these functionalised scaffolds are fused into a single molecule, the biological potency of the new molecule is predicted to have increased activity. The dispiro nitrogen containing heterocyclic compounds are usually prepared by a 1, 3 dipolar cycloaddition reaction [14e18] of an olefin dipolarophile azomethine ylide with a particular substrate especially with a five-membered heterocycles such as substituted pyrrolidines [19]. When this reaction is performed in a multi- component system, the creation of chemical archives of potent drug-like compounds is possible which might be used in combi- natorial chemistry for their profiling [20]. These dispiro heterocy- cles containing two sp 3 carbon atom, with different cyclic moieties, are biologically important [21] molecules. The spiro oxindole are important pharmacological agents which display pronounced cell- type-specific anti-cancer properties [22]. Typical examples are Horsfiline [23] which is a natural product, spirotryptostatine A and B [24] and NITD 609 which is a non-peptide inhibitor of MDM2-p53 [25,26] (Fig. 1). Since the 1, 3 cycloaddition of azomethine ylide with an acety- lenic dipolarophile is one of the most effective approaches for the regio- and stereo selective construction of a variety of complex spiro-oxindole derivatives [27] including a quinoline based mole- cule [28]. Quinolines display potent biological activity hence the 1, 3 cycloaddition reaction was selected for the synthesis of novel dispiro heterocyclic derivatives containing the quinoline moiety. * Corresponding author. E-mail address: genganrm@dut.ac.za (R.M. Gengan). Contents lists available at ScienceDirect Journal of Molecular Structure journal homepage: http://www.elsevier.com/locate/molstruc http://dx.doi.org/10.1016/j.molstruc.2017.08.017 0022-2860/© 2017 Elsevier B.V. All rights reserved. Journal of Molecular Structure 1149 (2017) 439e451