Synthesis and characterization of novel 1,2-oxazine-based small molecules that targets acetylcholinesterase

Synthesis and characterization of novel 1,2-oxazine-based small molecules that targets acetylcholinesterase Full article

Journal

Bioorganic & Medicinal Chemistry Letters
ISSN: 1464-3405 , E-ISSN: 0960-894X

Output data

Year: 2014, Volume: 24, Number: 15, Pages: 3618-3621 Pages count : 4 DOI: 10.1016/j.bmcl.2014.05.040

Authors

Sukhorukov Alexey Yu. ¹ , Nirvanappa Anilkumar C. ² , Swamy Jagadish ³ , Ioffe Sema L. ¹ , Nanjunda Swamy Shivananju ⁴ , Basappa _ ² , Rangappa Kanchugarakoppal S. ³

Affiliations

1	N.D. Zelinsky Institute of Organic Chemistry, Leninsky Prospect, 47, Moscow 119991, Russia
2	Laboratory of Chemical Biology, Department of Chemistry, Bangalore University, Palace Road, Bangalore 560001, India
3	Department of Chemistry, University of Mysore, Manasagangotri, Mysore 560001, India
4	Department of Biotechnology, Sri Jayachamarajendra College of Engineering, JSS, Technical Institutions Campus, Mysore 570006, India

Thirteen 2-oxazine-based small molecules were synthesized targeting 5-lipoxygenase (LOX), and acetylcholinesterase (AChE). The test revealed that the newly synthesized compounds had potent inhibition towards both 5-LOX and AChE in lower micro molar concentration. Among the tested compounds, the most active compound, 2-[(2-acetyl-6,6-dimethyl-4-phenyl-5,6-dihydro-2H-1,2-oxazin-3-yl)methyl]-1H-isoindole-1,3(2H)-dione (2a) showed inhibitory activity towards 5-LOX and AChE with an IC50 values of 1.88, and 2.5 μM, respectively. Further, the in silico molecular docking studies revealed that the compound 2a bound to the catalytic domain of AChE strongly with a highest CDOCKER score of −1.18 kcal/mol when compared to other compounds of the same series. Additionally, 2a showed a good lipophilicity (log P = 2.66), suggesting a potential ability to penetrate the blood–brain-barrier. These initial pharmacological data revealed that the compound 2a could serve as a drug-seed in developing anti-Alzheimer’s agents.

Sukhorukov A.Y. , Nirvanappa A.C. , Swamy J. , Ioffe S.L. , Nanjunda Swamy S. , Basappa _. , Rangappa K.S.
Synthesis and characterization of novel 1,2-oxazine-based small molecules that targets acetylcholinesterase
Bioorganic & Medicinal Chemistry Letters. 2014. V.24. N15. P.3618-3621. DOI: 10.1016/j.bmcl.2014.05.040 WOS Scopus OpenAlex

Web of science:	WOS:000339228700084
Scopus:	2-s2.0-84903975823
OpenAlex:	W2053981167

DB	Citing
OpenAlex	22
Scopus	27
Web of science	18