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New cyclopentaquinoline hybrids with multifunctional capacities for the treatment of Alzheimer's disease.
J Enzyme Inhib Med Chem. 2017 Dec; 33(1):158-170.JE

Abstract

Alzheimer's disease (AD) is the most common progressive form of brain neurodegeneration and the most prevailing cause of dementia. Unfortunately, the aetiology of AD is not completely studied but different factors are associated with the development of AD such as among others low level of acetylcholine, aggregation of β-amyloid (Aβ), hyperphosphorylated tau protein, oxidative stress, and inflammation. The study encompass organic syntheses of 2,3-dihydro-1H-cyclopenta[b]quinoline with 5,6-dichloronicotinic acid and suitable linkers derivatives as multifunctional agents for AD treatment. Afterwards self-induced amyloid beta aggregation, inhibition studies of acetylcholinesterase and butyrylcholinesterase and molecular docking studies were performed. The results showed that 3b compound exhibited the best acetylcholinesterase inhibitory activity, with IC50 value of 0.052 µM which is lower compared to references. Besides, all synthesised compounds showed good butyrylcholinesterase inhibitory activity with IC50 values from 0.071 to 0.797 µM. Compound 3b exhibited strong Aβ1-42 aggregation inhibitory effect with 25.7% at 5 µM to 92.8% at 100 µM as well as good anti-inflammatory effect. Thus, new compounds could create new perspectives for further development as a multi-target-directed agent for AD treatment.

Authors+Show Affiliations

a Department of Pharmaceutical Chemistry, Drug Analyses and Radiopharmacy, Faculty of Pharmacy , Medical University of Lodz , Lodz , Poland.a Department of Pharmaceutical Chemistry, Drug Analyses and Radiopharmacy, Faculty of Pharmacy , Medical University of Lodz , Lodz , Poland.a Department of Pharmaceutical Chemistry, Drug Analyses and Radiopharmacy, Faculty of Pharmacy , Medical University of Lodz , Lodz , Poland.b Department of Medicinal Chemistry, Faculty of Pharmacy , Medical University of Lublin , Lublin , Poland.c Department of Physicochemical Drug Analysis, Chair of Pharmaceutical Chemistry, Faculty of Pharmacy , Jagiellonian University Medical College , Krakow , Poland.c Department of Physicochemical Drug Analysis, Chair of Pharmaceutical Chemistry, Faculty of Pharmacy , Jagiellonian University Medical College , Krakow , Poland.d Department of Clinical Chemistry and Biochemistry , Medical University of Lodz , Lodz , Poland.d Department of Clinical Chemistry and Biochemistry , Medical University of Lodz , Lodz , Poland.d Department of Clinical Chemistry and Biochemistry , Medical University of Lodz , Lodz , Poland.a Department of Pharmaceutical Chemistry, Drug Analyses and Radiopharmacy, Faculty of Pharmacy , Medical University of Lodz , Lodz , Poland.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29210299

Citation

Czarnecka, Kamila, et al. "New Cyclopentaquinoline Hybrids With Multifunctional Capacities for the Treatment of Alzheimer's Disease." Journal of Enzyme Inhibition and Medicinal Chemistry, vol. 33, no. 1, 2017, pp. 158-170.
Czarnecka K, Girek M, Maciejewska K, et al. New cyclopentaquinoline hybrids with multifunctional capacities for the treatment of Alzheimer's disease. J Enzyme Inhib Med Chem. 2017;33(1):158-170.
Czarnecka, K., Girek, M., Maciejewska, K., Skibiński, R., Jończyk, J., Bajda, M., Kabziński, J., Sołowiej, P., Majsterek, I., & Szymański, P. (2017). New cyclopentaquinoline hybrids with multifunctional capacities for the treatment of Alzheimer's disease. Journal of Enzyme Inhibition and Medicinal Chemistry, 33(1), 158-170. https://doi.org/10.1080/14756366.2017.1406485
Czarnecka K, et al. New Cyclopentaquinoline Hybrids With Multifunctional Capacities for the Treatment of Alzheimer's Disease. J Enzyme Inhib Med Chem. 2017;33(1):158-170. PubMed PMID: 29210299.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - New cyclopentaquinoline hybrids with multifunctional capacities for the treatment of Alzheimer's disease. AU - Czarnecka,Kamila, AU - Girek,Małgorzata, AU - Maciejewska,Karolina, AU - Skibiński,Robert, AU - Jończyk,Jakub, AU - Bajda,Marek, AU - Kabziński,Jacek, AU - Sołowiej,Przemysław, AU - Majsterek,Ireneusz, AU - Szymański,Paweł, PY - 2017/12/7/entrez PY - 2017/12/7/pubmed PY - 2017/12/20/medline KW - Acetylcholinesterase inhibitors KW - Alzheimer’s disease KW - dementia KW - multifunctional drugs SP - 158 EP - 170 JF - Journal of enzyme inhibition and medicinal chemistry JO - J Enzyme Inhib Med Chem VL - 33 IS - 1 N2 - Alzheimer's disease (AD) is the most common progressive form of brain neurodegeneration and the most prevailing cause of dementia. Unfortunately, the aetiology of AD is not completely studied but different factors are associated with the development of AD such as among others low level of acetylcholine, aggregation of β-amyloid (Aβ), hyperphosphorylated tau protein, oxidative stress, and inflammation. The study encompass organic syntheses of 2,3-dihydro-1H-cyclopenta[b]quinoline with 5,6-dichloronicotinic acid and suitable linkers derivatives as multifunctional agents for AD treatment. Afterwards self-induced amyloid beta aggregation, inhibition studies of acetylcholinesterase and butyrylcholinesterase and molecular docking studies were performed. The results showed that 3b compound exhibited the best acetylcholinesterase inhibitory activity, with IC50 value of 0.052 µM which is lower compared to references. Besides, all synthesised compounds showed good butyrylcholinesterase inhibitory activity with IC50 values from 0.071 to 0.797 µM. Compound 3b exhibited strong Aβ1-42 aggregation inhibitory effect with 25.7% at 5 µM to 92.8% at 100 µM as well as good anti-inflammatory effect. Thus, new compounds could create new perspectives for further development as a multi-target-directed agent for AD treatment. SN - 1475-6374 UR - https://www.unboundmedicine.com/medline/citation/29210299/New_cyclopentaquinoline_hybrids_with_multifunctional_capacities_for_the_treatment_of_Alzheimer's_disease_ L2 - https://www.tandfonline.com/doi/full/10.1080/14756366.2017.1406485 DB - PRIME DP - Unbound Medicine ER -