Preclinical evaluation and molecular docking of 4-phenyl-1-Napthyl phenyl acetamide (4P1NPA) from Streptomyces sp. DPTB16 as a potent antifungal compound

The incidence of fungal disease has increased dramatically over the past decades, mainly due to the emergence and transmission of antifungal resistance within the fungal pathogens. The present study investigates the use of novel antifungal compound 4-Phenyl-1-Napthyl Phenyl Acetamide (4P1NPA), isolated from marine Streptomyces sp. DPTB16 as a potent antifungal drug. The preclinical studies and molecular docking for 4P1NPA against Cytochrome P450 51 (CYP 51) were performed using in silico pharmacology and docking tools. The finding reveals the drug likeliness of 4P1NPA and satisfactory interaction of 4P1NPA with CYP 51. These results collectively evidence the use of 4P1NPA as a drug to treat fungal infections. On the whole, we highlight the findings of this research will be helpful to design 4P1NPA as novel antifungal drug to defend the emerging antifungal resistance.

[1]  J. Perfect,et al.  Resistance to Antifungal Agents : Mechanisms and Clinical Impact , 2007 .

[2]  Haitao Ji,et al.  New azoles with potent antifungal activity: design, synthesis and molecular docking. , 2009, European journal of medicinal chemistry.

[3]  N. Thajuddin,et al.  AN ANTIFUNGAL COMPOUND: 4' PHENYL -1-NAPTHYL -PHENYL ACETAMIDE FROM STREPTOMYCES SP. DPTB16 , 2008 .

[4]  F. Lombardo,et al.  Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. , 2001, Advanced drug delivery reviews.

[5]  Carla D'Angeli,et al.  In-Silico Prediction of Drug Properties in Man Using Preclinical Data and Computer-Assisted Drug Development , 2001 .

[6]  M. Waterman,et al.  CYP51 from Trypanosoma brucei is obtusifoliol-specific. , 2004, Biochemistry.

[7]  Honggang Hu,et al.  Synthesis, Molecular Docking, and Biological Evaluation of Novel Triazole Derivatives as Antifungal Agents , 2010, Chemical biology & drug design.

[8]  Y. Aoyama.  Recent progress in the CYP51 research focusing on its unique evolutionary and functional characteristics as a diversozyme P450. , 2005, Frontiers in Bioscience.

[9]  J. Thornton,et al.  PROCHECK: a program to check the stereochemical quality of protein structures , 1993 .

[10]  J. Arthur.  The MDCK cell line is made up of populations of cells with diverse resistive and transport properties. , 2000, Tissue & cell.

[11]  David W. Ritchie,et al.  Ultra-fast FFT protein docking on graphics processors , 2010, Bioinform..

[12]  F. D. D'Auria,et al.  Antifungal activity of ketoconazole and other azoles againstMalassezia furfur in vitro andin vivo , 1997, Infection.

[13]  F. Dromer,et al.  Antifungal drug resistance in pathogenic fungi. , 1998, Medical mycology.

[14]  Jürgen Bajorath,et al.  Bio- and chemo-informatics beyond data management: crucial challenges and future opportunities. , 2002, Drug discovery today.

[15]  P. Wakeley,et al.  Synthesis , 2013, The Role of Animals in Emerging Viral Diseases.

[16]  M. Ghannoum,et al.  Antifungal Agents: Mode of Action, Mechanisms of Resistance, and Correlation of These Mechanisms with Bacterial Resistance , 1999, Clinical Microbiology Reviews.

[17]  Jie Liang,et al.  CASTp: Computed Atlas of Surface Topography of proteins , 2003, Nucleic Acids Res..

[18]  G. Quindós,et al.  Antifungal agents: mode of action in yeast cells. , 2006, Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia.

[19]  H. Schaller.  The role of sterols in plant growth and development. , 2003, Progress in lipid research.

[20]  Sean Ekins,et al.  Reengineering the pharmaceutical industry by crash-testing molecules. , 2005, Drug discovery today.

[21]  Donna A Volpe,et al.  Variability in Caco-2 and MDCK cell-based intestinal permeability assays. , 2008, Journal of pharmaceutical sciences.

[22]  M. Waterman,et al.  Small-Molecule Scaffolds for CYP51 Inhibitors Identified by High-Throughput Screening and Defined by X-Ray Crystallography , 2007, Antimicrobial Agents and Chemotherapy.