title: Structure Optimization of Neuraminidase Inhibitors as Potential Anti-Influenza (H1N1Inhibitors) Agents Using QSAR and Molecular Docking Studies.
abstract: The urgent need of neuraminidase inhibitors (NI) has provided an impetus for understanding the structure requisite at molecular level. Our search for selective inhibitors of neuraminidase has led to the identification of pharmacophoric requirements at various positions around acyl thiourea pharmacophore. The main objective of present study is to develop selective NI, with least toxicity and drug like ADMET properties. Electronic, Steric requirements were defined using kohnone nearest neighbour- molecular field analysis (kNN-MFA) model of 3D-QSAR studies. Results generated by QSAR studies showed that model has good internal as well as external predictivity. Such defined requirements were used to generate new chemical entities which exhibit higher promising predicted activities. To check selective binding of designed NCE's docking studies were carried out using the crystal structure of the neuraminidase enzyme having co-crystallized ligand Oseltamivir. Thus, molecular modelling provided a good platform to optimize the acyl thiourea pharmacophore for designing its derivatives having potent anti-viral activity.
authors.affiliation: Department of Pharmaceutical Chemistry- PG Wing, AISSMS College of Pharmacy, Pune-01, Maharashtra, India.
authors.forename: Poonam
authors.initials: P
authors.lastname: Inamdar
authors.affiliation: Department of Pharmaceutical Chemistry- PG Wing, AISSMS College of Pharmacy, Pune-01, Maharashtra, India.
authors.forename: Shashikant
authors.initials: S
authors.lastname: Bhandari
authors.affiliation: Department of Pharmaceutical Chemistry- PG Wing, AISSMS College of Pharmacy, Pune-01, Maharashtra, India.
authors.forename: Bhagyashri
authors.initials: B
authors.lastname: Sonawane
authors.affiliation: Department of Pharmaceutical Chemistry- PG Wing, AISSMS College of Pharmacy, Pune-01, Maharashtra, India.
authors.forename: Asha
authors.initials: A
authors.lastname: Hole
authors.affiliation: Department of Pharmaceutical Chemistry- PG Wing, AISSMS College of Pharmacy, Pune-01, Maharashtra, India.
authors.forename: Chintamani
authors.initials: C
authors.lastname: Jadhav
keywords: Anti-influenza agents; Drug design; Molecular Modelling; Neuraminidase Inhibitors; Optimization
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