Available online www.jocpr.com Journal of Chemical and Pharmaceutical Research, 2013, 5(10):337-341 Research Article ISSN : 0975-7384 CODEN(USA) : JCPRC5 337 Molecular docking analysis of natural compounds as Human neutrophil elastase (HNE) inhibitors Radhakrishnan Narayanaswamy 1 , Lam Kok Wai 2 and Intan Safinar Ismail 1,3* 1 Laboratory of Natural Products, Institute of Bioscience (IBS), Universiti Putra Malaysia (UPM), Serdang, Selangor, Malaysia 2 Faculty of Pharmacy, Universiti Kebangsaan Malaysia (UKM), Jalan Raja Muda Abdul Aziz, Kuala Lumpur, Malaysia 3 Department of Chemistry, Faculty of Science, Universiti Putra Malaysia (UPM), Serdang, Selangor, Malaysia _____________________________________________________________________________________________ ABSTRACT In recent years regulation of the enzymatic activity of human neutrophil elastase (HNE) has been the main focus of investigation, due to its potential therapeutic application in medicinal field. In the present study, the docking behaviour of human neutrophil elastase (HNE) with 14 different ligands namely Chrotacumines-A, B, C, Grandols- B, D, G, Rohitukine, Quercitin, Ellagic acid, Artoindonesianin-F, Origanol-A Thymoquinone, Embelin and Vilangin was evaluated along with their putative binding sites using Discovery Studio Version 3.1. In addition, molecular descriptors analysis using Molinspiration online tool was also carried out. The molecular physicochemical analysis revealed that Quercitin, Artoindonesianin-F & Origanol-A violated the five rules of thumb. With regard to drug- likeness property, Thymoquinone exhibited better score compared to all other ligands. Docking studies and binding free energy calculations revealed that Vilangin has maximum interaction energy (-50.1 kcal/mol) and Thymoquinone with the least interaction energy (-18.1 kcal/mol) as compared to the other investigated ligands. Quercitrin is the only ligand showed interaction with Ser 195 amino acid residue. Therefore, it is strongly suggested that the present study outcomes might provide new insight in understanding these 14 ligands, as potential candidates for human neutrophil elastase (HNE) inhibitory activity. Key words: Molecular physicochemical properties, Molecular docking, Chrotacumines, Grandols, Rohitukine, Embelin. _____________________________________________________________________________________________ INTRODUCTION Elastases belong to family of serine proteases that possess the ability to cleave or hydrolytic the extracellular matrix protein, notably elastin, which is widely distributed in vertebrate tissue especially abundant in the lung, arteries, skin and ligaments of human beings [1]. Human neutrophil elastase (HNE) is a proteolytic enzyme involved in the response to inflammatory stimuli [2] and it is present in azurophilic granules of neutrophils. In generally, HNE extracellular activity is regulated under normal physiological conditions by endogenous inhibitors such as α1- proteinase inhibitor (α1PI) and α-macroglobulin. However, during several pathological conditions such as acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF) and as well as other inflammatory associate disorders such as atherosclerosis, psoriasis and dermatitis, elevated HNE activity is commonly reported. In recent years, HNE has also been implicated in the progression of non-small cell lung cancer progression [3]. Hence, a number of clinical observations indicated that HNE represents a good therapeutic target for the treatment of inflammatory diseases and might also be valuable therapeutic agents in lung cancer [4].