Correlated changes in neuronal cerebral rat brain RNA synthesis and hypo- and hypermotoric disorders induced by 6-aminonicotinamide (6-AN)

Knoll-Köhler, E; Wojnorowicz, F.; Sarkander, H.-I.

doi:10.1007/bf00236738

Cited by 7 publications

(2 citation statements)

References 37 publications

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“…The cultures were subjected to either 6AN or compound 5i at 5 or 50 μM for 24 h. Treatment with 6AN at both 5 and 50 μM led to a significant increase in the percentage of cells that were positive for TUNEL staining compared to the DMSO control (Figure ). This result is consistent with the previously reported neurotoxicity of 6AN. ,− In contrast, neither 5 nor 50 μM treatment of compound 5i led to a significant increase in TUNEL-positive cells compared with DMSO-treated cells. Taken together, these data demonstrate that compound 5i does not cause significant neurotoxicity at concentrations that reverse the epigenetic and metabolic changes in the distant metastatic pancreatic carcinoma.…”

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confidence: 93%

“…Given the well-documented neurotoxicity of 6AN, ,− we investigated whether compound 5i retains the neurotoxic properties of 6AN using primary rat hippocampal neurons. The cultures were subjected to either 6AN or compound 5i at 5 or 50 μM for 24 h. Treatment with 6AN at both 5 and 50 μM led to a significant increase in the percentage of cells that were positive for TUNEL staining compared to the DMSO control (Figure ).…”

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confidence: 99%

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Effects of 6-Aminonicotinic Acid Esters on the Reprogrammed Epigenetic State of Distant Metastatic Pancreatic Carcinoma

Gao

Tallon

Feinberg

et al. 2022

ACS Med. Chem. Lett.

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In the search for alternatives to 6-aminonicotinamide (6AN), a series of 6-aminonicotinic acid esters were designed and synthesized as precursors of 6-amino-NADP+, a potent inhibitor of 6-phosphogluconate dehydrogenase (6PGD). Like 6AN, some of these esters were found to reverse the loss of histone 3 lysine 9 trimethylation (H3K9me3) in patient-derived pancreatic ductal adenocarcinoma (PDAC) distant metastasis (A38-5). Among them, 1-(((cyclohexyloxy)carbonyl)oxy)ethyl 6-aminonicotinate (5i) showed more potent antiproliferative activity than 6AN. Metabolite analysis revealed that compound 5i produced a marked increase in metabolites upstream of 6PGD, indicating intracellular inhibition of 6PGD by 6-amino-NADP+ derived from compound 5i through 6-aminonicotinic acid (6ANA) via the Preiss–Handler pathway. Despite the more potent pharmacological effects shown by compound 5i in A38-5, compound 5i was found to be substantially less toxic to primary hippocampal rat neurons compared to 6AN, indicating its therapeutic potential in targeting distant metastatic cells.

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confidence: 99%