The mutagenicity of a new anthracycline (moflomycin) with potent antileukemic activity was studied by the Ames test in four strains of Salmonella typhimurium (TA97a, TA98, TA100 and TA102), and compared to the mutagenicity of doxorubicin, widely used as antineoplastic agent. Unlike doxorubicin, moflomycin displayed no mutagenic activity in strains TA98 and TA100. Low mutagenicity was only observed in TA102 strain and was not enhanced after metabolic activation. This result indicates that moflomycin induce mutagenicity by reverting base-pair substitution. The structural changes in the sugar moiety may be involved in the reduced mutagenicity of moflomycin. The low mutagenicity of moflomycin shown in this study enhances the potential advantage of this new derivative which displays a high antileukemic activity.
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http://dx.doi.org/10.1016/0165-1218(95)00052-6 | DOI Listing |
Front Pharmacol
January 2025
Department of Surgical Sciences, Functional Pharmacology and Neuroscience, Uppsala University, Uppsala, Sweden.
Background: Xanthones are dubbed as putative lead-like molecules for cancer drug design and discovery. This study was aimed at the synthesis, characterization, and target fishing of novel xanthone derivatives.
Methods: The products of reactions of xanthydrol with urea, thiourea, and thiosemicarbazide reacted with α-haloketones to prepare the thiazolone compounds.
Eur J Med Chem
December 2024
Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 N. Pine St., Baltimore, MD, 21201, USA; University of Maryland Marlene & Stewart Greenebaum Comprehensive Cancer Center, 22 S. Greene St., Baltimore, MD, 21201, USA. Electronic address:
Current treatments for acute myeloid leukemias (AMLs) cure fewer than 30 % of patients. This low efficacy is due, in part, to the inter-patient and intra-patient heterogeneity of AMLs; accordingly, all current AML treatment regimens involve drug combinations (polypharmacy). A recently-completed clinical trial in relapsed/refractory AML using a combination of two newer targeted antileukemics, the BCL-2 inhibitor venetoclax (VEN) plus the FLT3 inhibitor gilteritinib (GIL), yielded highly promising results for this two-drug polypharmacy combination.
View Article and Find Full Text PDFActa Pharm Sin B
December 2024
School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China.
The fat mass and obesity-associated protein (FTO) is an RNA demethylase required for catalytic demethylation of -methyladenosine (mA); it is highly expressed and functions as an oncogene in acute myeloid leukemia (AML). Currently, the overarching objective of targeting FTO is to precisely inhibit the catalytic activity. Meanwhile, whether FTO degradation also exerts antileukemic effects remains unknown.
View Article and Find Full Text PDFBiotechnol Bioeng
January 2025
Chair of Technical Biochemistry, Technische Universität Dresden, Dresden, Saxony, Germany.
Ikarugamycin is a member of the natural product family of the polycyclic tetramate macrolactams (PoTeMs). The compound exhibits a diverse range of biological activities, including antimicrobial, antiprotozoal, anti-leukemic, and anti-inflammatory properties. In addition, it interferes with several crucial cellular functions, such as oxidized low-density lipoprotein uptake in macrophages, Nef-induced CD4 cell surface downregulation, and mechanisms of endocytosis.
View Article and Find Full Text PDFBlood
December 2024
Department of Hematology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with a poor prognosis and limited options for targeted therapies. Identifying new molecular targets to develop novel therapeutic strategies is the pressing immediate issue in T-ALL. Here, we observed high expression of WD Repeat-Containing Protein 5 (WDR5) in T-ALL; with in vitro and in vivo models we demonstrated the oncogenic role of WDR5 in T-ALL by activating cell cycle signaling through its new downstream effector, ATPase family AAA domain-containing 2 (ATAD2).
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