Assessing the differential action on cancer cells of LDH-A inhibitors based on the N-hydroxyindole-2-carboxylate (NHI) and malonic (Mal) scaffolds.
نویسندگان
چکیده
A head-to-head study of representative examples of N-hydroxyindole-2-carboxylates (NHI) and malonic derivatives (Mal) as LDH-A inhibitors was conducted, comparing the enzyme inhibition potency, cellular uptake, reduction of lactate production in cancer cells and anti-proliferative activity. Among the compounds tested, methyl 1-hydroxy-6-phenyl-4-(trifluoromethyl)-1H-indole-2-carboxylate (2, NHI-2), a methyl ester belonging to the NHI class, displayed optimal properties in the cell-based assays, proving to be an efficient anti-glycolytic agent against cancer cells.
منابع مشابه
The comparison of the effect of different inhibitors on aromatase enzyme effective in the breast cancer by molecular docking method
Background: Aromatase is an enzyme that plays an important role in the development of estrogen-positive breast cancer. Estrogens are essential in human and mainly in women because of their role in sexual development and reproduction. Adverse effects of some aromatase inhibitors increase the need to discover new inhibitors with higher selectivity, lower toxicity and improved potency. In this stu...
متن کاملEffect of Nanoclay Addition on the Properties of Polycaprolactone Nanocomposite Scaffolds Containing Adipose Derived Mesenchymal Stem Cells used in Soft Tissue Engineering
Tissue-engineering scaffolds provide biological and mechanical frameworks for cell adhesion, growth, and differentiation. Nanofibrous scaffolds mimic the native extracellular matrix (ECM) and play a significant role in formation and remodeling of tissues and/or organs . One way to mimic the desired properties of fibrous ECM is adding nanoparticles into the polymer matrix. In the current study, ...
متن کاملDiscovery of N-hydroxyindole-based inhibitors of human lactate dehydrogenase isoform A (LDH-A) as starvation agents against cancer cells.
Highly invasive tumor cells are characterized by a metabolic switch, known as the Warburg effect, from "normal" oxidative phosphorylation to increased glycolysis even under sufficiently oxygenated conditions. This dependence on glycolysis also confers a growth advantage to cells present in hypoxic regions of the tumor. One of the key enzymes involved in glycolysis, the muscle isoform of lactate...
متن کاملSynthesis and biological evaluation of non-glucose glycoconjugated N-hydroyxindole class LDH inhibitors as anticancer agents.
Inhibitors of human lactate dehydrogenase A (LDH-A) are promising therapeutic agents against cancer. The development of LDH-A inhibitors that possess cellular activities has so far proved to be particularly challenging, since the enzyme's active site is narrow and highly polar. In the recent past, we were able to develop a glucose-conjugated N-hydroxyindole-based LDH-A inhibitor designed to exp...
متن کاملProgress in HIV-1 integrase inhibitors: A review of their chemical structure diversity
HIV-1 integrase (IN) enzyme, one of the three main enzymes of HIV-1, catalyzed the insertion of the viral DNA into the genome of host cells. Because of the lack of its homologue in human cells and its essential role in HIV-1 replication, IN inhibition represents an attractive therapeutic target for HIV-1 treatment. Since identification of IN as a promising therapeutic target, a major progress h...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Organic & biomolecular chemistry
دوره 11 38 شماره
صفحات -
تاریخ انتشار 2013