title: In silico screening for identification of novel β-1,3-glucan synthase inhibitors using pharmacophore and 3D-QSAR methodologies.
abstract: The enzyme β-1,3-glucan synthase, which catalyzes the synthesis of β-1,3-glucan, an essential and unique structural component of the fungal cell wall, has been considered as a promising target for the development of less toxic anti-fungal agents. In this study, a robust pharmacophore model was developed and structure activity relationship analysis of 42 pyridazinone derivatives as β-1,3-glucan synthase inhibitors were carried out. A five-point pharmacophore model, consisting of two aromatic rings (R) and three hydrogen bond acceptors (A) was generated. Pharmacophore based 3D-QSAR model was developed for the same reported data sets. The generated 3D-QSAR model yielded a significant correlation coefficient value (R (2) = 0.954) along with good predictive power confirmed by the high value of cross-validated correlation coefficient (Q (2) = 0.827). Further, the pharmacophore model was employed as a 3D search query to screen small molecules database retrieved from ZINC to select new scaffolds. Finally, ADME studies revealed the pharmacokinetic efficiency of these compounds.
authors.affiliation: Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad, 500046 India.
authors.forename: Potshangbam Angamba
authors.initials: PA
authors.lastname: Meetei
authors.affiliation: Bioinformatics Infrastructure Facility, School of Life Sciences, University of Hyderabad, Hyderabad, 500046 India ; Centre for Biological Sciences, School of Earth, Biological and Environmental Sciences, Central University of South Bihar, Patna, 800014 India.
authors.forename: R S
authors.initials: RS
authors.lastname: Rathore
authors.affiliation: Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad, 500046 India.
authors.forename: N Prakash
authors.initials: NP
authors.lastname: Prabhu
authors.affiliation: Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad, 500046 India ; Bioinformatics Infrastructure Facility, School of Life Sciences, University of Hyderabad, Hyderabad, 500046 India.
authors.forename: Vaibhav
authors.initials: V
authors.lastname: Vindal
keywords: 3D-QSAR; ADME; Pharmacophore; Virtual screening; β-1,3-Glucan synthase