Synthesis and Structure-Activity Relationship Study of Tacrine-Based Pyrano[2,3-C]Pyrazoles Targeting Ache/Buche and 15-Lox

Synthesis and Structure-Activity Relationship Study of Tacrine-Based Pyrano[2,3-C]Pyrazoles Targeting Ache/Buche and 15-Lox Publisher Pubmed

Pourabdi L¹ ; Khoobi M^{2, 3} ; Nadri H⁴ ; Moradi A⁴ ; Moghadam FH⁵ ; Emami S⁶ ; Mojtahedi MM¹ ; Haririan I² ; Forootanfar H⁷ ; Ameri A⁸ ; Foroumadi A³ ; Shafiee A³

Show Affiliations

1. Department of Organic Chemistry and Natural Products, Chemistry and Chemical Engineering Research Center of Iran, Pajohesh Blvrd., 17th Km of Tehran Karaj Highway, P.O. Box 14335-186, Tehran, Iran
2. Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
3. Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, 14176, Iran
4. Department of Medicinal Chemistry, Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
5. Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
6. Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
7. Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
8. Department of Medicinal Chemistry, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran

Source: European Journal of Medicinal Chemistry Published:2016

Abstract

A series of tacrine-based pyrazolo[4′,3′:5,6]pyrano[2,3-b]quinolines and related compounds were designed and synthesized for targeting AChE, BuChE and 15-LOX enzymes in the field of Alzheimer's disease therapy. Most of compounds showed potent activity against cholinesterases and mild potency toward 15-LOX enzyme. In particular, compounds 29, 32 and 40 displayed inhibition at nano-molar level against AChE and BuChE (IC50s = 0.005–0.08 μM), being more potent than reference drug tacrine. Moreover, compound 32 with IC50value of 31 μM was the most potent compound against 15-LOX. The cytotoxicity assay on HepG2 cells revealed that compounds 29 and 32 showed no significant cytotoxic activity even at concentration of 50 μM. The cytotoxicity of compounds 29 and 32 was significantly less than that of tacrine at higher concentrations. © 2016 Elsevier Masson SAS

Style	Citing Format
MLA	Pourabdi L, et al.. "Synthesis and Structure-Activity Relationship Study of Tacrine-Based Pyrano[2,3-C]Pyrazoles Targeting Ache/Buche and 15-Lox." European Journal of Medicinal Chemistry, vol. 123, no. , 2016, pp. 298-308.
APA	Pourabdi L, Khoobi M, Nadri H, Moradi A, Moghadam FH, Emami S, Mojtahedi MM, Haririan I, Forootanfar H, Ameri A, Foroumadi A, Shafiee A (2016). Synthesis and Structure-Activity Relationship Study of Tacrine-Based Pyrano[2,3-C]Pyrazoles Targeting Ache/Buche and 15-Lox. European Journal of Medicinal Chemistry, 123(), 298-308.
Chicago	Pourabdi L, Khoobi M, Nadri H, Moradi A, Moghadam FH, Emami S, Mojtahedi MM, et al.. "Synthesis and Structure-Activity Relationship Study of Tacrine-Based Pyrano[2,3-C]Pyrazoles Targeting Ache/Buche and 15-Lox." European Journal of Medicinal Chemistry 123, no. (2016): 298-308.
Harvard	Pourabdi L et al. (2016) 'Synthesis and Structure-Activity Relationship Study of Tacrine-Based Pyrano[2,3-C]Pyrazoles Targeting Ache/Buche and 15-Lox', European Journal of Medicinal Chemistry, 123(), pp. 298-308.
Vancouver	Pourabdi L, Khoobi M, Nadri H, Moradi A, Moghadam FH, Emami S, et al.. Synthesis and Structure-Activity Relationship Study of Tacrine-Based Pyrano[2,3-C]Pyrazoles Targeting Ache/Buche and 15-Lox. European Journal of Medicinal Chemistry. 2016;123():298-308.
BibTex	@article{ author = {Pourabdi L and Khoobi M and Nadri H and Moradi A and Moghadam FH and Emami S and Mojtahedi MM and Haririan I and Forootanfar H and Ameri A and Foroumadi A and Shafiee A}, title = {Synthesis and Structure-Activity Relationship Study of Tacrine-Based Pyrano[2,3-C]Pyrazoles Targeting Ache/Buche and 15-Lox}, journal = {European Journal of Medicinal Chemistry}, volume = {123}, number = {}, pages = {298-308}, year = {2016} }
RIS	TY - JOUR AU - Pourabdi L AU - Khoobi M AU - Nadri H AU - Moradi A AU - Moghadam FH AU - Emami S AU - Mojtahedi MM AU - Haririan I AU - Forootanfar H AU - Ameri A AU - Foroumadi A AU - Shafiee A TI - Synthesis and Structure-Activity Relationship Study of Tacrine-Based Pyrano[2,3-C]Pyrazoles Targeting Ache/Buche and 15-Lox JO - European Journal of Medicinal Chemistry VL - 123 IS - SP - 298 EP - 308 PY - 2016 ER -

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