Polycyclic Tetramate Macrolactams and Their Potential as Anticancer Agents
Alexandria Montavon, M. Raquel Marchán-Rivadeneira, Yong Han
Organics · pp. 361–377 · Published 27 Sep 2024
10.3390/org5040019Abstract
Natural products have been a reliable source of drug compounds in medical research. Technological advances have led to the discovery and characterization of many compounds that were previously difficult to isolate. However, when searching for anticancer drugs, finding natural compounds that can bind to specific targets is a daunting task. Polycyclic tetramate macrolactams (PoTeMs), specifically, have been a source of antibiotics for a long time, though they possess certain cytotoxic properties that make them attractive candidates for anticancer drug discovery. This review covers the structural diversity and widespread availability of PoTeM compounds and the past research that demonstrates their effects on human cancer cell lines. Additionally, this review documents the known receptors and molecular mechanisms of these compounds in mammalian cells.
References (45)
- 1 Demain, 2014, Importance of microbial natural products and the need to revitalize their discovery [DOI]
- 2 David, 2015, The pharmaceutical industry and natural products: Historical status and new trends [DOI]
- 3 Atanasov, 2021, Natural products in drug discovery: Advances and opportunities [DOI]
- 4 Siegel, 2024, Cancer statistics, 2024 [DOI]
- 5 Sun, 2023, Targeting GDP-Dissociation Inhibitor Beta (GDI2) with a Benzo[a]quinolizidine Library to Induce Paraptosis for Cancer Therapy [DOI]
- 6 Huang, 2021, Natural Products in Cancer Therapy: Past, Present and Future [DOI]
- 7 Zheng, 2016, Novel Benzo[a]quinolizidine Analogs Induce Cancer Cell Death through Paraptosis and Apoptosis [DOI]
- 8 Wang, H., He, Y., Jian, M., Fu, X., Cheng, Y., He, Y., Fang, J., Li, L., and Zhang, D. (2022). Breaking the Bottleneck in Anticancer Drug Development: Efficient Utilization of Synthetic Biology. Molecules, 27. [DOI]
- 9 Surade, 2012, Structural biology and drug discovery of difficult targets: The limits of ligandability [DOI]
- 10 Mallinson, 2012, Macrocycles in new drug discovery [DOI]
- 11 Liu, W., Zhang, W., Jin, H., Zhang, Q., Chen, Y., Jiang, X., Zhang, G., Zhang, L., Zhang, W., and She, Z. (2019). Genome Mining of Marine-Derived Streptomyces sp. SCSIO 40010 Leads to Cytotoxic New Polycyclic Tetramate Macrolactams. Mar. Drugs, 17. [DOI]
- 12 Blodgett, 2010, Common biosynthetic origins for polycyclic tetramate macrolactams from phylogenetically diverse bacteria [DOI]
- 13 Luo, 2013, Activation and characterization of a cryptic polycyclic tetramate macrolactam biosynthetic gene cluster [DOI]
- 14 Medema, 2021, Mining genomes to illuminate the specialized chemistry of life [DOI]
- 15 Ding, W., Tu, J., Zhang, H., Wei, X., Ju, J., and Li, Q. (2021). Genome Mining and Metabolic Profiling Uncover Polycyclic Tetramate Macrolactams from Streptomyces koyangensis SCSIO 5802. Mar. Drugs, 19. [DOI]
- 16 Mo, 2014, Naturally occurring tetramic acid products: Isolation, structure elucidation and biological activity [DOI]
- 17 Lowery, 2009, Defining the mode of action of tetramic acid antibacterials derived from Pseudomonas aeruginosa quorum sensing signals [DOI]
- 18 Bodenschatz, 2022, A synthetic approach to 5/5/6-polycyclic tetramate macrolactams of the discodermide type [DOI]
- 19 Xu, 2015, Bioactive Polycyclic Tetramate Macrolactams from Lysobacter enzymogenes and Their Absolute Configurations by Theoretical ECD Calculations [DOI]
- 20 Saha, 2017, Activation and characterization of a cryptic gene cluster reveals a cyclization cascade for polycyclic tetramate macrolactams [DOI]
- 21 Jin, 2020, Engineered Biosynthesis of 5/5/6 Type Polycyclic Tetramate Macrolactams in an Ikarugamycin (5/6/5 Type)-Producing Chassis [DOI]
- 22 Li, 2018, Biosynthesis of the Polycyclic System in the Antifungal HSAF and Analogues from Lysobacter enzymogenes [DOI]
- 23 Li, 2019, OX4 Is an NADPH-Dependent Dehydrogenase Catalyzing an Extended Michael Addition Reaction to Form the Six-Membered Ring in the Antifungal HSAF [DOI]
- 24 Harper, C.P., Day, A., Tsingos, M., Ding, E., Zeng, E., Stumpf, S.D., Qi, Y., Robinson, A., Greif, J., and Blodgett, J.A.V. (2024). Critical analysis of polycyclic tetramate macrolactam biosynthetic gene cluster phylogeny and functional diversity. Appl. Environ. Microbiol., 90. [DOI]
- 25 Yan, 2021, Combinatorial Biosynthesis of Oxidized Combamides Using Cytochrome P450 Enzymes from Different Polycyclic Tetramate Macrolactam Pathways [DOI]
- 26 Jiang, 2023, A Mechanistic Understanding of the Distinct Regio- and Chemoselectivity of Multifunctional P450s by Structural Comparison of IkaD and CftA Complexed with Common Substrates [DOI]
- 27 DeVita, 2012, Two hundred years of cancer research [DOI]
- 28 Sullivan, 2015, Global cancer surgery: Delivering safe, affordable, and timely cancer surgery [DOI]
- 29 Craver, 1952, Recent advances in treatment of inoperable cancer
- 30 Aoki, 2000, Melophlins A and B, novel tetramic acids reversing the phenotype of ras-transformed cells, from the marine sponge Melophlus sarassinorum [DOI]
- 31 Birnie, 1988, The HL60 cell line: A model system for studying human myeloid cell differentiation
- 32 Li, 2023, Discovery and biosynthesis of pseudoamides reveal enzymatic cyclization of the polyene precursor to 5–5 bicyclic tetramate macrolactams [DOI]
- 33 Chen, 2024, Discovery of Aburatubolactams Reveals Biosynthetic Logic for Distinct 5/5-Type Polycyclic Tetramate Macrolactams [DOI]
- 34 Dhaneesha, 2019, DNA Binding and Molecular Dynamic Studies of Polycyclic Tetramate Macrolactams (PTM) with Potential Anticancer Activity Isolated from a Sponge-Associated Streptomyces zhaozhouensis subsp. mycale subsp. nov [DOI]
- 35 Khoo, 1988, Enhanced macrophage uptake of low density lipoprotein after self-aggregation [DOI]
- 36 Gui, Y., Zheng, H., and Cao, R.Y. (2022). Foam Cells in Atherosclerosis: Novel Insights into Its Origins, Consequences, and Molecular Mechanisms. Front. Cardiovasc. Med., 9. [DOI]
- 37 Poznyak, A.V., Nikiforov, N.G., Markin, A.M., Kashirskikh, D.A., Myasoedova, V.A., Gerasimova, E.V., and Orekhov, A.N. (2021). Overview of OxLDL and its impact on cardiovascular health: Focus on atherosclerosis. Front. Pharmacol., 11. [DOI]
- 38 Hasumi, 1992, Inhibition of the uptake of oxidized low-density lipoprotein in macrophage J774 by the antibiotic ikarugamycin [DOI]
- 39 Elkin, 2016, Ikarugamycin: A Natural Product Inhibitor of Clathrin-Mediated Endocytosis [DOI]
- 40 Motley, 2003, Clathrin-mediated endocytosis in AP-2-depleted cells [DOI]
- 41 Luo, 2001, Human immunodeficiency virus type 1 Nef-induced CD4 cell surface downregulation is inhibited by ikarugamycin [DOI]
- 42 Popescu, 2011, Ikarugamycin induces DNA damage, intracellular calcium increase, p38 MAP kinase activation and apoptosis in HL-60 human promyelocytic leukemia cells [DOI]
- 43 Bertasso, 2020, Ripromycin and other polycyclic macrolactams from Streptomyces sp. Tu 6239: Taxonomy, fermentation, isolation and biological properties [DOI]
- 44 Jiang, 2020, Ikarugamycin inhibits pancreatic cancer cell glycolysis by targeting hexokinase 2
- 45 Minamidate, A., Onizawa, M., Saito, C., Hikichi, R., Mochimaru, T., Murakami, M., Sakuma, C., Asakawa, T., Hiraoka, Y., and Oshima, S. (2021). A potent endocytosis inhibitor Ikarugamycin up-regulates TNF production. Biochem. Biophys. Rep., 27. [DOI]
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