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Relevant academic research and scientific papers

Synthesis of new 2,3-disubstituted 4-chloro-1-hydroxyindoles

The syntheses of new 2,3-disubstituted 4-chloro-1-hydroxyindoles were described. The conjugate nitro ketoester was reacted with various thiol and alcohol nucleophiles by the action of stannous chloride dihydrate through the unique processes of reduction o

One-pot synthesis of novel multisubstituted 1-alkoxyindoles

Studies on a one-pot synthesis of novel multisubstituted 1-alkoxyindoles 1 and their mechanistic investigations are presented. The synthesis of 1 was successfully achieved through consecutive four step reactions from substrates 2. The substrates 2, prepar

Synthesis and Antiproliferative Activities of 1-Hydroxyindole-2-Carboxylates

Synthesis and evaluation of antiproliferative activities of 1-hydroxyindole-2-carboxylates 1 were described. The toluene compounds 3 were treated with dimethyl oxalate and then, dimethylmethyleneammonium chloride to give intermediates 2. Compounds 2 were

Synthesis of New 1-Hydroxyindole-2-Carboxylates and Mechanistic Studies on Reaction Pathways

Synthesis of new 1-hydroxyindole-2-carboxylates 1 and mechanistic studies on the reaction pathways were described. The substrates 2, prepared through two-step synthetic sequences, were treated with nucleophiles in the presence of SnCl2 · 2H2O to obtain compounds 1. In particular, the mechanistic studies led to a significant finding that reactions with thiol nucleophiles occur through a newly proposed pathway (path B: 1,4-addition followed by reduction/condensation) rather than through a previously assumed pathway (path A: reduction/condensation followed by 1,5-addition). Further mechanistic investigations revealed steric effects of o-substituents in 2 governing the ratio of products (1i/7).

Synthesis of new highly substituted and hindered 1-hydroxyindole-2-carboxylates

The synthesis of new, highly substituted, and hindered 1-hydroxyindole-2-carboxylates 1 is described. Substrates 2, prepared through a two-step synthetic sequence, were treated with relatively weak nucleophiles in the presence of SnCl2 · 2H2O to afford compounds 1. In particular, nucleophiles of low reactivity and/or high steric hindrance reacted efficiently to give 1 in good to modest yields.

Discovery 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 dehydrogenase (LDH-A), is overexpressed by metastatic cancer cells and is linked to the vitality of tumors in hypoxia. This enzyme may be considered as a potential target for new anticancer agents, since its inhibition cuts cancer energetic and anabolic supply, thus reducing the metastatic and invasive potential of cancer cells. We have discovered new and efficient N-hydroxyindole-based inhibitors of LDH-A, which are isoform-selective (over LDH-B) and competitive with both the substrate (pyruvate) and the cofactor (NADH). The antiproliferative activity of these compounds was confirmed on a series of cancer cell lines, and they proved to be particularly effective under hypoxic conditions. Moreover, NMR experiments showed that these compounds are able to reduce the glucose-to-lactate conversion inside the cell.