Aclarubicin Hydrochloride is a second-generation anthracycline compound produced by Streptomyces galilaeus that has antibacterial and anti-cancer properties. It is a fluorescent molecule that has specificity for the chymotrypsin-like activity of the 20S proteasome. Aclarubicin is soluble in DMSO and DMF and insoluble in water.
|Mechanism of Action||Aclarubicin prevents nucleic acid synthesis by intercalating between DNA and RNA base pairs and inhibiting topoisomerase I and II, an enzyme that relaxes supercoiled DNA.Aclarubicin prevents nucleic acid synthesis by intercalating between DNA and RNA base pairs and inhibiting topoisomerase I and II, an enzyme that relaxes supercoiled DNA.|
|Cancer Applications|| |
Aclarubicin is used for cancer research including lymphoma, leukemia, and lung cancer. In one study, Aclarubicin alleviated vasoconstriction in rat aorta and was shown to be less cardiotoxic than doxorubicin and daunorubicin.
Aclarubicin was studied in a clonogenic assay using the human small cell lung cancer cell line OC-NYH along with an MDR murine subline of Ehrlich ascites tumor (EHR2/DNR+). When used in combination with daunorubicin, it was able to mediate the cytotoxicity induced by daunorubicin due interaction with topoisomerase II (Jensen et al, 1991).
Aclarubicin emitted fluorescence and human cervical cancer HeLa cells exposed to Aclarubicin exhibited bright fluorescence signals in the cytoplasm when fluorescence microscopy was done. It accumulates in the mitochondria of living human cells and leads to dysfunction, implying a previously overlooked cytotoxicity of Aclarubicin in the cytoplasm and adding mechanistic insight into its anti-cancer activity (Iihoshi H et al, 2017).
Jensen PB et al (1991) Antagonistic effect of aclarubicin on daunorubicin-induced cytotoxicity in human small cell lung cancer cells: relationship to DNA integrity and topoisomerase II. Cancer Res. 51(19):5093–5099 PMID 1655244
Jensen PB (1994) Postincubation with Aclarubicin Reverses Topoisomerase II Mediated DNA Cleavage, Strand Breaks, and Cytotoxicity Induced by VP-16. Investigational New Drugs12:289-97 PMID 7775129