review · Food Science & Nutrition
Acute myeloid leukaemia is a complex blood malignancy driven by disrupted cell growth, differentiation, and death, with treatment often hindered by therapeutic resistance and relapse. A systematic evaluation of scientific literature identified over sixty bioactive compounds capable of serving as potential drug leads against the disease. These compounds span five primary categories: flavonoids, alkaloids, organosulfur compounds, terpenes and terpenoids, alongside other emerging bioactive molecules. The documented modes of action vary significantly among the individual molecules. Reported biological activities include disrupting chromatin architecture, enhancing the synthesis of specific DNA repair proteins, and prompting cell cycle arrest as well as programmed cell death. Furthermore, these substances function through the modulation or inhibition of key cellular regulators, such as heat shock protein 90, DNA methyltransferase 1, and histone deacetylase 1.
Current clinical treatments for acute myeloid leukaemia, including conventional chemotherapy and targeted therapies, frequently encounter drug resistance and patient relapse. Identifying diverse naturally derived bioactive compounds offers alternative pathways for anti-leukaemic drug discovery. Understanding the distinct cellular mechanisms targeted by these molecules provides researchers with critical biochemical templates to develop therapies capable of overcoming established clinical treatment barriers.
This work highlights chemical leads for pharmaceutical developers and drug discovery teams seeking candidates to address treatment-resistant acute myeloid leukaemia. Because the findings derive from a systematic review compiling laboratory-level mechanisms, the identified compounds represent early-stage discovery assets. Further preclinical validation, chemical optimisation, and pharmacokinetic assessment are necessary before any of these bioactive molecules can progress into formal translational pipelines or clinical testing.
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This systematic review identified various bioactive compounds which have the potential to serve as novel drugs or leads against acute myeloid leukemia. Acute myeloid leukemia (AML) is a heterogeneous hematopoietic malignancy that arises from the dysregulation of cell differentiation, proliferation, and cell death. The risk factors associated with the onset of AML include long-term exposure to radiation and chemicals such as benzene, smoking, genetic disorders, blood disorders, advancement in age, and others. Although novel strategies to manage AML, including a refinement of the conventional chemotherapy regimens, hypomethylating agents, and molecular targeted drugs, have been developed in recent years, resistance and relapse remain the main clinical problems. In this study, three databases, PubMed/MEDLINE, ScienceDirect, and Google Scholar, were systematically searched to identify various bioactive compounds with antileukemic properties. A total of 518 articles were identified, out of which 59 were viewed as eligible for the current report. From the data extracted, over 60 bioactive compounds were identified and divided into five major groups: flavonoids, alkaloids, organosulfur compounds, terpenes, and terpenoids, and other known and emerging bioactive compounds. The mechanism of actions of the analyzed individual bioactive molecules differs remarkably and includes disrupting chromatin structure, upregulating the synthesis of certain DNA repair proteins, inducing cell cycle arrest and apoptosis, and inhibiting/regulating Hsp90 activities, DNA methyltransferase 1, and histone deacetylase 1.
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DOI: 10.1002/fsn3.3420
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