Tổng hợp các hợp chất bis-heterocyclic chứa thieno[2,3-b]thiophene - Các dẫn xuất dược lý mới

International Journal of Molecular Sciences - Tập 14 Số 3 - Trang 5712-5722
Yahia N. Mabkhot1, Assem Barakat2, Abdullah Mohammed Al‐Majid3, M. Iqbal Choudhary3
1Department of Chemistry, Faculty of Science, King Saud University, P. O. Box 2455, Riyadh 11451, Saudi Arabia. [email protected]
2Hussain Ebrahim Jamal Research Institute of Chemistry
3King Saud University

Tóm tắt

Các dẫn xuất thiênethiofen đại diện cho một lớp hợp chất quan trọng với nhiều hoạt tính sinh học khác nhau. Chúng tôi mô tả ở đây quy trình tổng hợp một loạt hợp chất mới chứa thieno[2,3-b]thiophene 3–7. Tất cả các hợp chất đã được đánh giá về tiềm năng chống oxy hóa in vitro, khả năng ức chế α-glucosidase và β-glucuronidase cũng như hoạt tính chống ung thư đối với dòng tế bào PC-3. Các hợp chất 2b (IC50 = 1.3 ± 0.2 μM), 5a (IC50 = 2.3 ± 0.4 μM) và 5b (IC50 = 8.7 ± 0.1 μM) cho thấy khả năng ức chế mạnh mẽ enzyme β-glucuronidase, hoạt động hiệu quả hơn so với tiêu chuẩn d-saccharic acid 1,4-lactone (IC50 = 45.8 ± 2.5 μM). Các hợp chất 5a (IC50 = 22.0 ± 0.3 μM) và 5b (IC50 = 58.4 ± 1.2 μM) cũng cho thấy khả năng ức chế α-glucosidase mạnh mẽ so với thuốc tiêu chuẩn (acarbose, IC50 = 841 ± 1.7 μM).

Từ khóa


Tài liệu tham khảo

Heeney, 2005, Stable polythiophene semiconductors incorporating thieno[2,3-b]thiophene, J. Am. Chem. Soc, 127, 1078, 10.1021/ja043112p

Mashraqui, 2006, Synthesis and structures of thieno[2,3-b]thiophene incorporated [3,3]dithiacyclophanes. Enhanced first hyperpolarizability in an unsymmetrically polarized cyclophane, Tetrahedron Lett, 47, 5599, 10.1016/j.tetlet.2006.05.098

Mashraqui, 2005, Dipyridyl/Pyridinium thieno[2,3-b]thiophenes as new atropisomeric systems. Synthesis, conformat-ional analysis and energy minimization, Tetrahedron, 61, 3507, 10.1016/j.tet.2005.01.123

Leriche, 2003, Linearly extended tetrathiafulvalene analogues with fused thiophene units as π conjugated spacers, J. Mater. Chem, 13, 1324, 10.1039/B301149F

Lee, 2005, Ring-Sulfonated poly(thienothiophene), J. Adv. Mater, 17, 1792, 10.1002/adma.200500210

Lim, 2005, Thin-Film morphologies and solution-processable field-effect transistor behavior of a fluorine-thieno[3,2-b]thiophene-based conjugated copolymer, Macromolecules, 38, 4531, 10.1021/ma048128e

Kim, 2007, Synthesis and studies on 2-hexylthieno[3,2-b]thiophene end-capped oligomers for OTFTs, Chem. Mater, 19, 3561, 10.1021/cm070053g

Jarak, 2006, Novel cyano- and amidino-substituted derivatives of thieno[2,3-b]- and thien-o[3,2-b]thiophene-2-carboxanilides and thieno[30,20:4,5]thieno- and thieno[20,30:4,5]thieno[2,3-c]quinolones: Synthesis, photochemical synthesis, DNA binding, and antitumor evaluation, Bioorg. Med. Chem, 14, 2859, 10.1016/j.bmc.2005.12.004

Peters, 1990, Synthesis of various 5-substituted uracils, J. Heterocycl. Chem, 27, 2165, 10.1002/jhet.5570270756

Kukolja, 1985, Orally absorbable cephalosporin antibiotics. 2. Structure-Activity studies of bicyclic glycine derivatives of 7-aminodeacetoxycephalosporanic acid, J. Med. Chem, 28, 1896, 10.1021/jm00150a023

Prugh, 1991, New isomeric classes of topically active ocular hypotensive carbonic anhydrase inhibitors: 5-Substituted thieno[2,3-b]thiophene-2-sulfonamides and 5-substituted thieno[3,2-b]thiophene-2-sulfonamides, J. Med. Chem, 34, 1805, 10.1021/jm00110a008

Egbertson, 1999, Centrally constrained thienothiophene α-sulfonamides are potent, long acting in vivo inhibitors of platelet aggregation, J. Med. Chem, 42, 2409, 10.1021/jm980722p

Allard, 2008, Organic semiconductors for solution-processable field-effect transistors (OFETs), Angew. Chem. Int. Ed, 47, 4070, 10.1002/anie.200701920

Wu, 2010, Synthesis of poly(3-alkylthiophene)-block-poly( arylisocyanide): Two sequential, mechanistically distinct polymerizations using a single catalyst, J. Am. Chem. Soc, 132, 14000, 10.1021/ja106999q

Li, 2011, Synthesis and self-assembly of poly(3-hexylthiophene)-block-poly(acrylic acid), Chem. Commun, 47, 197, 10.1039/C0CC02166K

Wu, 2011, Polythiophene-block-poly(γ-benzyl l-glutamate): Synthesis and study of a new rod-rod block copolymer, Polym. Chem, 2, 300, 10.1039/C0PY00299B

Sirringhaus, 1999, Two-Dimensional charge transport in self-organized, high-mobility conjugated polymers, Nature, 401, 685, 10.1038/44359

Schuett, 1962, The paralytic shellfish poison. Degradation to a pyrrolopyrimidine, J. Am. Chem. Soc, 84, 2266, 10.1021/ja00870a056

Ho, 2007, 5-(1-Pyrrolyl)-2-phenylthieno[2,3-d]pyrimidine as building block in heterocyclic synthesis: Novel synthesis of some pyrazoles, pyrimidines, imidazo[1,2-a]pyrimidines, pyrazolo[1,5-a]pyrimidines, pyrido-(pyrimido)pyrazolo[1,5-a]pyrimidines, 1,2,4-triazolo[1,5-a]pyrimidine and a 1,2,3,4-tetrazolo[1,5-a]pyrimidine derivative, J. Chin. Chem. Soc, 54, 1075, 10.1002/jccs.200700154

Alexander, 2006, Novel one pot synthesis of polysubstituted pyrazolo[1,5-a] and imidazo[1,2-a]pyrimidines, Tetrahedron Lett, 47, 2611, 10.1016/j.tetlet.2006.02.031

Riyadh, 2011, Enaminones as building blocks for the synthesis of substituted pyrazoles with antitumor and antimicrobial activities, Molecules, 16, 1834, 10.3390/molecules16021834

Mabkhot, 2011, 1,1′-(3-Methyl-4-phenylthieno[2,3-b]thiophene-2,5-diyl)diethanone as a building block in heterocyclic synthesis. Novel synthesis of some pyrazole and pyrimidine derivatives, Molecules, 16, 6502, 10.3390/molecules16086502

Mosmann, 1983, Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays, J. Immunol. Meth, 65, 55, 10.1016/0022-1759(83)90303-4

Khan, 2012, 2,4,6-Trichlorophenylhydrazine Schiff bases as DPPH radical and super oxide anion scavengers, Med. Chem, 8, 452, 10.2174/1573406411208030452

Khan, 2011, Synthesis of novel inhibitors of β-glucuronidase based on benzothiazole skeleton and study of their binding affinity by molecular docking, Bioorg. Med. Chem., 19, 4286, 10.1016/j.bmc.2011.05.052

Choudhary, 2011, Cyclopeptide alkaloids of Ziziphus oxyphylla Edgw as novel inhibitors of α-glucosidase enzyme and protein glycation, Phytochem. Lett., 4, 404, 10.1016/j.phytol.2011.08.006