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

Eur J Med Chem. 2014 Sep 12:84:739-45. doi: 10.1016/j.ejmech.2014.07.065. Epub 2014 Jul 21.

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.

Keywords: Anticancer activity; Antimicrobial activity; Breast cancer cell line; Diethyl 2,5-diaminothiophene-3,4-dicarboxylate; PTP-1B inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Antifungal Agents / chemical synthesis
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Candida albicans / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • Drug Evaluation, Preclinical
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Escherichia coli / drug effects
  • HeLa Cells
  • Humans
  • Hypoglycemic Agents / chemical synthesis
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / pharmacology*
  • MCF-7 Cells
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
  • Staphylococcus aureus / drug effects
  • Structure-Activity Relationship
  • Thiophenes / chemical synthesis
  • Thiophenes / chemistry
  • Thiophenes / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Antifungal Agents
  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Hypoglycemic Agents
  • Thiophenes
  • diethyl 2-amino-5-(((4-nitrophenyl)methylidene)amino)thiophene-3,4-dicarboxylate
  • diethyl 2-amino-5-(((5-nitrofuran-2-yl)methylidene)amino)thiophene-3,4-dicarboxylate
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1