ArticleCurrent organic synthesis2025
The Conjugation of Chlorambucil with 4-Phenylbutanoic Acid and Valproic Acid respectively for Enhancing Anti-tumor Activity.
Article in Current organic synthesis, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
Abstract
backgroundNitrogen mustards exert their anticancer activity by alkylating DNA. However, except for alkylating DNA, nitrogen mustards may alkylate other biomolecules to cause off-target effects due to their highly active functional groups. So, more exposure of DNA from chromosomes can facilitate the binding of nitrogen mustards to DNA to present stronger anticancer activity, simultaneously avoiding more side effects.
objectivesTo design and synthesize the 4-phenylbutanoic acid-chlorambucil conjugates and valproic acid-chlorambucil conjugates. Upon cellular internalization, the two conjugates can more strongly damage the DNA of cancer cells due to the more exposure of cellular DNA caused by 4-phenylbutanoic acid or valproic acid.
methodsTo validate this hypothesis, we designed and synthesized two hybrids of chlorambucil with 4-phenylbutanoic acid and valproic acid, denoted as compound 2a and compound 2b respectively. The antitumor activity of the aforementioned hybrids was evaluated by the MTT method, mitochondrial membrane potential analysis, apoptosis assay, DNA damage assay, and scratch assay respectively.
resultsCompound 2a and compound 2b were synthesized via esterification. The results of bioactivity evaluation showed compound 2a and compound 2b had stronger cytotoxicity against breast cancer MDA-MB-231 cells and MCF-7 cells than chlorambucil. More importantly, toward triple negative breast cancer MDA-MB-231 cells, compound 2a exhibited significantly greater cytotoxicity compared to both compound 2b and chlorambucil. Further studies were conducted on MDA-MB-231 cells, showing that compound 2a could more strongly decrease the mitochondrial membrane potential, induce cell apoptosis, and damage cellular DNA compared to compound 2b and chlorambucil. Interestingly, in combating the migration of MDA-MB-231 cells, the results exhibited that compound 2b had a much stronger anti-migratory effect than compound 2a, inconsistent with the aforementioned in vitro cytotoxicity.
conclusionThese findings demonstrate that the combination of nitrogen mustards with histone deacetylase inhibitors is an effective strategy to exert synergistic anti-tumor effects.
Indexed as
Identifiers
39950290What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.