Synthesis, Characterization, Hirshfeld Surface Analysis, Crystal Structure and Molecular Modeling Studies of 1-(4-(Methoxy(phenyl)methyl)-2-methylphenoxy)butan-2-one Derivative as a Novel α-Glucosidase Inhibitor
Chandra Shivanna,
Shashank M. Patil,
C. Mallikarjunaswamy,
Ramith Ramu,
Prabhuswamy Akhileshwari,
Latha Rani Nagaraju,
Mandayam A. Sridhar,
Shaukath Ara Khanum,
V. Lakshmi Ranganatha,
Ekaterina Silina,
Victor Stupin,
Raghu Ram Achar
Affiliations
Chandra Shivanna
Department of Physics, The National Institute of Engineering, Manandavadi Road, Mysore 570008, India
Shashank M. Patil
Department of Biotechnology and Bioinformatics, JSS Academy of Higher Education and Research, Mysuru 570015, India
C. Mallikarjunaswamy
Postgraduate Department of Chemistry, JSS College of Arts, Commerce and Science, JSS Research Centre (A Recognized Research Centre of University of Mysore), Mysuru 570025, India
Ramith Ramu
Department of Biotechnology and Bioinformatics, JSS Academy of Higher Education and Research, Mysuru 570015, India
Prabhuswamy Akhileshwari
Department of Studies in Physics, University of Mysore, Manasagangotri, Mysuru 570006, India
Latha Rani Nagaraju
Department of Studies in Physics, University of Mysore, Manasagangotri, Mysuru 570006, India
Mandayam A. Sridhar
Department of Studies in Physics, University of Mysore, Manasagangotri, Mysuru 570006, India
Shaukath Ara Khanum
Department of Chemistry, Yuvaraja’s College, University of Mysore, Mysore 570005, India
V. Lakshmi Ranganatha
Department of Chemistry, The National Institute of Engineering, Manandavadi Road, Mysore 570008, India
Ekaterina Silina
Department of Human Pathology, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia
Victor Stupin
Department of Hospital Surgery 1, N.I. Pirogov Russian National Research Medical University (RNRMU), 117997 Moscow, Russia
Raghu Ram Achar
Division of Biochemistry, School of Life Sciences, JSS Academy of Higher Education and Research, Mysuru 570015, India
The crystal compound was synthesized and characterized using conventional analytical techniques. The compound C19H21O3 crystallizes in a monoclinic crystal system with the space group P21/c. The crystal structure is stabilized by C-H…O interactions. The structure is further reinforced by π-π interactions. During in vitro inhibition of α-glucosidase, the crystal compound exhibited a significant inhibition of the enzyme (IC50: 10.30 ± 0.25 µg/mL) in comparison with the control, acarbose (IC50: 12.00 ± 0.10 µg/mL). Molecular docking studies were carried out for the crystal compound with the α-glucosidase protein model, which demonstrated that the crystal molecule has a good binding affinity (−10.8 kcal/mol) compared with that of acarbose (−8.2 kcal/mol). The molecular dynamics simulations and binding free energy calculations depicted the stability of the crystal molecule throughout the simulation period (100 ns). Further, a Hirshfeld analysis was carried out in order to understand the packing pattern and intermolecular interactions. The energy difference between the frontier molecular orbitals (FMO) was 4.95 eV.
