Computational design syntheses and Biological evaluation of chalcones Hydrazones and thiosemicarbazones as Anticancer agents

Abstract

This research work focuses on the identification of simple organic molecules as newlinechemotherapeutic agents. It comprises the design, syntheses and biological newlineevaluation of three unique classes of compounds chalcones, hydrazones and newlinethiosemicarbazones. Simple condensation reactions were utilised to prepare all newlinethe compounds and spectroscopic techniques such as UV-Visible, FTIR, Mass, newline1H and 13C NMR were used to confirm their structures. Twelve of the compounds newlinewere crystallised and analysed using single crystal X-ray diffraction technique. newlineEach class of compounds was then subject to computational study via molecular newlinedocking, pharmacophore mapping and density functional theory studies. newlineMolecular docking was performed against and#946;-tubulin downloaded from the RCSB newlineProtein Data Bank website (www.rcsb.org). and#946;-tubulin is used in the assembly of newlinethe microtubule which is critical for cell division. Microtubules are important newlinecellular components that form the mitotic spindle during mitosis. Any disruption newlineof the spindle or the microtubule dynamics could lead to cell arrest and further newlineon, cell death. Hence, compounds that inhibit the tubulin-microtubule dynamics newlineare always considered important lead molecules in anticancer chemotherapy. This newlinethesis reports the effect of the three classes of compounds on and#946;-tubulin and its newlinepolymerisation with and#945;-tubulin into microtubules. These are called either Tubulin newlinebinding agents (TBAs) or anti-mitotic agents. The binding interactions of the title newlineix newlinecompounds against and#946;-tubulin were studied and their dock scores analysed. newlineAccelrys Discovery Studio software was used for the docking studies with newlineLigandFit protocol. The binding energy of the ligand-receptor complexes was newlinecalculated. The significant amino acid residues involved in the interactions were newlinealso analysed. Density Functional Theory studies were performed to study the newlineelectronic and geometric characteristics of the compounds. The HOMO and newlineLUMO energy levels with the band gaps were calculated. Guassian software was newlineused for the DFT