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Synthesis, characterization, and SAR of arylated indenoquinoline-based cholinesterase and carbonic anhydrase inhibitors.
Arch Pharm (Weinheim). 2018 Sep; 351(9):e1800167.AP

Abstract

We report the synthesis of bromoindenoquinolines (15a-f) by Friedlander reactions in low yields (13-50%) and the conversion of the corresponding phenyl-substituted indenoquinoline derivatives 16-21 in high yields (80-96%) by Suzuki coupling reactions. To explore the structure-activity relationship (SAR), their inhibition potentials to inhibit acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and human carbonic anhydrase cyctosolic (hCA I and II) enzymes were determined. Monophenyl (16-18) indenoquinolines significantly inhibited the AChE and BChE enzymes in ranges of IC50 37-57 nM and 84-93 nM, respectively, compared with their starting materials 15a-c and reference compounds (galanthamine and tacrine). On the other hand, these novel arylated indenoquinoline-based derivatives were effective inhibitors of the BChE, hCA I and II, BChE and AChE enzymes with Ki values in the range of 37 ± 2.04 to 88640 ± 1990 nM for AChE, 120.94 ± 37.06 to 1150.95 ± 304.48 nM for hCA I, 267.58 ± 98.05 to 1568.16 ± 438.67 nM for hCA II, and 84 ± 3.86 to 144120 ± 2910 nM for BChE. As a result, monophenyl indenoquinolines 16-18 may have promising anti-Alzheimer drug potential and 3,8-dibromoindenoquinoline amine (15f) can be novel hCA I and hCA II enzyme inhibitors.

Authors+Show Affiliations

Faculty of Art and Science, Department of Chemistry, Sakarya University, Serdivan, Turkey.Faculty of Art and Science, Department of Chemistry, Sakarya University, Serdivan, Turkey.Faculty of Education, Department of Maths and Science Education, Kırıkkale University, Kirikkale, Turkey.Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Bezmialem Vakif University, Istanbul, Turkey.Vocational School of Health Services, Cumhuriyet University, Sivas, Turkey.Faculty of Science, Department of Chemistry, Ataturk University, Erzurum, Turkey.Faculty of Pharmacy, Department of Pharmacognosy/Phytochemistry, Bezmialem Vakif University, Istanbul, Turkey.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30079554

Citation

Ekiz, Makbule, et al. "Synthesis, Characterization, and SAR of Arylated Indenoquinoline-based Cholinesterase and Carbonic Anhydrase Inhibitors." Archiv Der Pharmazie, vol. 351, no. 9, 2018, pp. e1800167.
Ekiz M, Tutar A, Ökten S, et al. Synthesis, characterization, and SAR of arylated indenoquinoline-based cholinesterase and carbonic anhydrase inhibitors. Arch Pharm (Weinheim). 2018;351(9):e1800167.
Ekiz, M., Tutar, A., Ökten, S., Bütün, B., Koçyiğit, Ü. M., Taslimi, P., & Topçu, G. (2018). Synthesis, characterization, and SAR of arylated indenoquinoline-based cholinesterase and carbonic anhydrase inhibitors. Archiv Der Pharmazie, 351(9), e1800167. https://doi.org/10.1002/ardp.201800167
Ekiz M, et al. Synthesis, Characterization, and SAR of Arylated Indenoquinoline-based Cholinesterase and Carbonic Anhydrase Inhibitors. Arch Pharm (Weinheim). 2018;351(9):e1800167. PubMed PMID: 30079554.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synthesis, characterization, and SAR of arylated indenoquinoline-based cholinesterase and carbonic anhydrase inhibitors. AU - Ekiz,Makbule, AU - Tutar,Ahmet, AU - Ökten,Salih, AU - Bütün,Burcu, AU - Koçyiğit,Ümit M, AU - Taslimi,Parham, AU - Topçu,Gülaçtı, Y1 - 2018/08/05/ PY - 2018/06/01/received PY - 2018/07/07/revised PY - 2018/07/11/accepted PY - 2018/8/7/pubmed PY - 2018/12/12/medline PY - 2018/8/7/entrez KW - SAR KW - acetylcholinesterase KW - bromoindenoquinolines KW - butyrylcholinesterase KW - carbonic anhydrase KW - enzyme inhibition KW - phenyl indenoquinolines SP - e1800167 EP - e1800167 JF - Archiv der Pharmazie JO - Arch. Pharm. (Weinheim) VL - 351 IS - 9 N2 - We report the synthesis of bromoindenoquinolines (15a-f) by Friedlander reactions in low yields (13-50%) and the conversion of the corresponding phenyl-substituted indenoquinoline derivatives 16-21 in high yields (80-96%) by Suzuki coupling reactions. To explore the structure-activity relationship (SAR), their inhibition potentials to inhibit acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and human carbonic anhydrase cyctosolic (hCA I and II) enzymes were determined. Monophenyl (16-18) indenoquinolines significantly inhibited the AChE and BChE enzymes in ranges of IC50 37-57 nM and 84-93 nM, respectively, compared with their starting materials 15a-c and reference compounds (galanthamine and tacrine). On the other hand, these novel arylated indenoquinoline-based derivatives were effective inhibitors of the BChE, hCA I and II, BChE and AChE enzymes with Ki values in the range of 37 ± 2.04 to 88640 ± 1990 nM for AChE, 120.94 ± 37.06 to 1150.95 ± 304.48 nM for hCA I, 267.58 ± 98.05 to 1568.16 ± 438.67 nM for hCA II, and 84 ± 3.86 to 144120 ± 2910 nM for BChE. As a result, monophenyl indenoquinolines 16-18 may have promising anti-Alzheimer drug potential and 3,8-dibromoindenoquinoline amine (15f) can be novel hCA I and hCA II enzyme inhibitors. SN - 1521-4184 UR - https://www.unboundmedicine.com/medline/citation/30079554/Synthesis_characterization_and_SAR_of_arylated_indenoquinoline_based_cholinesterase_and_carbonic_anhydrase_inhibitors_ L2 - https://doi.org/10.1002/ardp.201800167 DB - PRIME DP - Unbound Medicine ER -