In search of Tuberculosis drug design : An in silico approach to azoimidazolyl derivatives as antagonist for Cytochrome P450
Sayantan Pradhan, Sudipa Mondal, Chittaranjan Sinha · Zenodo (CERN European Organization for Nuclear Research) · 2016
Department of Chemistry, Inorganic Chemistry Section, Jadavpur University, Kolkata-700 032, India E-mail : [email protected] Fax : 91-33-2414658 Manuscript received online 04 January 2016, accepted 29 February 2016 Tuberculosis is a deadly disease and is caused by Mycobacterium tuberculosis (Mtb). Cytochrome P450s (CYPs) in the Mtb genome is playing important physiological role for its growth and survivability. Azole drugs have potent anti-mycobacterial activity and molecular docking studies indicate that CYP inhibition is the major target of the drugs. Out of six structures of CYPs in PDB (CYP51, CYP121, CYP124, CYP125, CYP130 and CYP142) CYP121 has shown better binding affinity with fluconazole, an antifungal medicine. In this work we have searched for a series of arylazoimidazole molecules, the structural analogue of fluconazole, those act as antagonist via in-silico approach with CYP121. It is calculated that arylazoimidazole ligands have better binding affinity and higher docking score compared to fluconazole and other available azole drugs. Most of the molecules have crossed the druglikeness filter though Lipinski’s rule and Ghosh’s rule. QSAR calculation has shown that there is positive correlation (R2 > 0.5) among the docking scores and molecular properties of the azole structure analogous. ADMET calculation has also shown that one of the arylazoimidazoles, (E)-6-((3-((1H-imidazol-2-yl)diazenyl)naphthalen-2-yl)amino)-2H-chromen-2-one (Molecular ID-85; Mol. wt., 453.54; docking score, –10.9; log P, 3.928), is best docked and druglikeness passed and crossed the barrier of ADMET filter.