In-Silico Design, Synthesis, Characterization and In Vitro Anti-tubercular Activity of Novel Cyclopentanone Analogues of Curcumin

Abstract

Curcumin is chemically 1,7-bis(4-hydroxy-3-methoxyphenyl) hepta-1,6-diene-3,5-dione found in turmeric as a yellow pigment. Major pharmacological actions of turmeric were mediated by the binding affinity of β-diketone found in this diaryl hepatanoid to various enzyme receptors in the human body. This study focuses on replacing this active pharmacophore with a cyclopentanone ring and evaluates the effect of terminal aryl rings on binding with a suitable anti-tubercular receptor. In this study, different proposed cyclopentanone analogues of curcumin were evaluated in silico by various software. 3D drawing of the proposed derivatives was done by ACD Lab Chemsketch 12.0. Drug likeness properties and obeying nature of proposed derivatives to Lipinski’s rule of five were analyzed by Molinspiration cheminformatics software. SwissADME and Protox-II software were used for the analysis of ADME and toxicity profile of proposed derivatives. PASS software was used for the screening of general biological activity and AutoDock Vina was used for the docking evaluation of proposed derivatives. Six among the 30 derivatives were selected for the synthesis with the help of these in-silico tools. The synthesized derivatives were characterized by various spectral methods. Anti-tubercular activity of synthesized compounds was evaluated by agar well diffusion method and minimum inhibitory concentration was determined by Resazurin micro titre assay method by using Mycobacterium smegmatis. Among the six tested derivatives two compounds named as CPP 1 and CPP 2 had possessing significant anti-tubercular activity. The polarity and hydrogen bond interactions that offered by pyridine ring could be reason for better pharmacological action reported by compounds CPP1 and CPP 2. Further studies on these molecules in the future may give more significant data.