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Densely substituted piperidines as a new class of elastase inhibitors: Synthesis and molecular modeling studies
Author(s) -
Hamdani Syeda S.,
Khan Bilal A.,
Saeed Aamer,
Larik Fayaz A.,
Hameed Shahid,
Channar Pervaiz A.,
Ahmad Khalil,
Mughal Ehsan Ullah,
Abbas Qamar,
Amin Noor Ul,
Ghumro Sarfaraz A.,
Maitlo Habibullah,
Hassan Mubashir,
Raza Hussain,
Seo SungYum
Publication year - 2019
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201900061
Subject(s) - piperidine , elastase , chemistry , trifluoromethyl , stereochemistry , enzyme , hydrogen bond , elastin , ic50 , molecular model , ligand (biochemistry) , pancreatic elastase , active site , biochemistry , organic chemistry , molecule , in vitro , receptor , medicine , alkyl , pathology
Elastase is the only enzyme that has the capability to degrade elastin and collagen, the two proteins essential for skin and bones. The synthesis of some densely substituted piperidines functionalized with the trifluoromethyl group ( 4a‐j ) was carried out. The newly prepared compounds were subjected to elastase enzyme inhibitory potential and antioxidant activity assays. Among the series, 4i (IC 50 = 0.341 ± 0.001 μM) exhibited the maximum inhibition against elastase. Binding analysis delineated that the fluorine atom of ligand 4i showed hydrogen and hydrophobic bonds with Thr41 and Thr96, with bond distances of 3.84 and 5.631 Å, respectively. The obtained results indicate that these trifluoromethyl functionalized piperidine derivatives could be considered as potential candidates to treat skin disorders.