Insight into the Structural Requirements of Theophylline-Based Aldehyde Dehydrogenase lAl (ALDHlAl) Inhibitors Through Multi-QSAR Modeling and Molecular Docking Approaches

Over expression of aldehyde dehydrogenase (ALDH1A1) is one of the vital hallmarks of the self-renewal and differentiational cancer stem cells (CSCs). Till now, no selective ALDH1A1 inhibitor is commercially available in the market. So there is an urgent need to explore some novel molecules which can selectively inhibit ALDH1A1 to combat cancer. Presently, our work deals with the development of QSAR models of some theophylline-based molecules by conventional 2D-QSAR, hologram QSAR (HQSAR), and Bayesian classification modeling. The descriptors identified from these QSAR models give avenues to modulate the structure of theophylline-based compounds to a desirable biological end point. Molecular docking study reveals the selectivity of these molecules towards ALDH1A1 (PDB: 4WP7) and important binding residues (GLY 125, 458; THR 129; TRP 178; TYR 297; PHE 171, 466; VAL 174, 460; MET 175; HIS 293 etc.) for the interaction with the receptors. The current study may help to design novel compounds as selective ALDH1A1 inhibitors.

Medienart:

E-Artikel

Erscheinungsjahr:

2016

Erschienen:

2016

Enthalten in:

Zur Gesamtaufnahme - volume:13

Enthalten in:

Current drug discovery technologies - 13(2016), 2 vom: 21., Seite 84-100

Sprache:

Englisch

Beteiligte Personen:

Abdul Amin, Sk [VerfasserIn]
Adhikari, Nilanjan [VerfasserIn]
Gayen, Shovanlal [VerfasserIn]
Jha, Tarun [VerfasserIn]

Themen:

ALDH1A1 protein, human
Aldehyde Dehydrogenase
Aldehyde Dehydrogenase 1 Family
C137DTR5RG
EC 1.2.1
EC 1.2.1.3
EC 1.2.1.36
Journal Article
Retinal Dehydrogenase
Theophylline

Anmerkungen:

Date Completed 03.10.2017

Date Revised 09.12.2020

published: Print

Citation Status MEDLINE

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM259906662