title: Discovery of diethyl 2,5-diaminothiophene-3,4-dicarboxylate derivatives as potent anticancer and antimicrobial agents and screening of anti-diabetic activity: synthesis and in vitro biological evaluation. Part 1.
abstract: Series of diethyl 2,5-diaminothiophene-3,4-dicarboxylate (DDTD) derivatives: azomethines of DDTD (2a-l) have been synthesized and screened for their anticancer, antimicrobial and anti-diabetic activities. The novel synthesized compounds were characterized by (1)H, (13)C NMR, MS and FT-IR analyses. All compounds were evaluated for their antiproliferative activity against three types of cancer cell line such as T47D and MCF-7 (human breast cancer), Hela (human cervical cancer) and Ishikawa (human endometrial cancer) lines. The results showed that most compounds exhibited significant antiproliferative activity against breast cancer cells. The majority of azomethines DDTD influenced strongly against breast cancer cells T47D and MCF-7, among them compounds 2b (2.3 μM), 2c (12.1 μM), 2e (13.2 μM), 2i (14.9 μM), 2j (16.0 μM), 2k (7.1 μM), 2l (8.6 μM) manifest potent anticancer activity against cancer cell T47D than Doxorubicin (DOX, 15.5 μM). Compound 2j has shown potent activity on all three types of cancer cells concurrently and IC50 values were considerably low in comparison with positive control DOX. In addition, all compounds were tested for antimicrobial activity against Staphylococcus aureus ATCC 6538 (Gram positive bacteria), Escherichia coli ATCC 11229 (Gram negative bacteria) and Candida albicans ATCC 10231 (Fungi) strains and 2j which contains in the ring nitrofurfural fragment, showed the highest effect on the three species of microbial pathogens simultaneously. Some compounds induced enzymatic inhibition in a concentration-dependent manner on PTP-1B inhibitor.
authors: Key Laboratory of Plant Resources and Chemistry in Arid Regions, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, South Beijing Road 40-1, Urumqi, Xinjiang 830011, PR China; Institute of the Chemistry of Plant Substances, Academy of Sciences of Uzbekistan, 77, Mirzo Ulugbek Str., 100170 Tashkent, Uzbekistan.
authors: Khurshed
authors: K
authors: Bozorov
authors: Key Laboratory of Plant Resources and Chemistry in Arid Regions, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, South Beijing Road 40-1, Urumqi, Xinjiang 830011, PR China.
authors: Hai-Rong
authors: HR
authors: Ma
authors: Key Laboratory of Plant Resources and Chemistry in Arid Regions, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, South Beijing Road 40-1, Urumqi, Xinjiang 830011, PR China.
authors: Jiang-Yu
authors: JY
authors: Zhao
authors: Key Laboratory of Plant Resources and Chemistry in Arid Regions, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, South Beijing Road 40-1, Urumqi, Xinjiang 830011, PR China.
authors: Hai-Qing
authors: HQ
authors: Zhao
authors: Key Laboratory of Plant Resources and Chemistry in Arid Regions, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, South Beijing Road 40-1, Urumqi, Xinjiang 830011, PR China.
authors: Hua
authors: H
authors: Chen
authors: Key Laboratory of Plant Resources and Chemistry in Arid Regions, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, South Beijing Road 40-1, Urumqi, Xinjiang 830011, PR China; Institute of the Chemistry of Plant Substances, Academy of Sciences of Uzbekistan, 77, Mirzo Ulugbek Str., 100170 Tashkent, Uzbekistan.
authors: Khayrulla
authors: K
authors: Bobakulov
authors: Key Laboratory of Plant Resources and Chemistry in Arid Regions, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, South Beijing Road 40-1, Urumqi, Xinjiang 830011, PR China.
authors: Xue-Lei
authors: XL
authors: Xin
authors: Institute of the Chemistry of Plant Substances, Academy of Sciences of Uzbekistan, 77, Mirzo Ulugbek Str., 100170 Tashkent, Uzbekistan.
authors: Burkhon
authors: B
authors: Elmuradov
authors: Institute of the Chemistry of Plant Substances, Academy of Sciences of Uzbekistan, 77, Mirzo Ulugbek Str., 100170 Tashkent, Uzbekistan.
authors: Khusnutdin
authors: K
authors: Shakhidoyatov
authors: Key Laboratory of Plant Resources and Chemistry in Arid Regions, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, South Beijing Road 40-1, Urumqi, Xinjiang 830011, PR China. Electronic address: haji@ms.xjb.ac.cn.
authors: Haji A
authors: HA
authors: Aisa
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D061986:MCF-7 Cells; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D013876:Thiophenes; C000596765:diethyl 2-amino-5-(((4-nitrophenyl)methylidene)amino)thiophene-3,4-dicarboxylate; C000596767:diethyl 2-amino-5-(((5-nitrofuran-2-yl)methylidene)amino)thiophene-3,4-dicarboxylate; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1
keywords: Anticancer activity; Antimicrobial activity; Breast cancer cell line; Diethyl 2,5-diaminothiophene-3,4-dicarboxylate; PTP-1B inhibitor