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Medicinal Mushrooms
Published in Anil K. Sharma, Raj K. Keservani, Surya Prakash Gautam, Herbal Product Development, 2020
Temitope A. Oyedepo, Adetoun E. Morakinyo
Polyketides are secondary metabolites with structurally complex organic compounds which are produced by most living organisms. Higher fungi are important producers of this metabolite (Volman et al., 2010b). Polyketides are extremely active biologically and this has made them to be a good source of drug discovery. Hence, many pharmaceuticals including antibiotic, anticancer, antifungal, hypolipidemic, and immunosuppressive drugs are derived from polyketides (Hung and Nhi, 2012; Staunton and Weissman, 2001).
Natural Polyketides to Prevent Cardiovascular Disease
Published in Catherina Caballero-George, Natural Products and Cardiovascular Health, 2018
This chapter will not attempt to address the numerous controversies that surround the use of statins with relation to cardiovascular disease and their associated side effects. Rather, the focus of this chapter is on the nature of statins, their structure and how they interact with relevant biological processes. This should provide some perspective on the use of polyketides as pharmaceuticals. While statin intervention may be straightforward life-or-death in a microbial world, these molecules operate in the context of a more complex system, the human body, which has carefully regulated mechanisms to maintain function. It becomes more difficult to predict how the introduction of statins will affect the organism as a whole. Regardless, statins have proven to be the most consistent and effective lipid-lowering agent on the market since their introduction and are a valuable case study for the role of polyketides in disease prevention.
Microalgae and Cyanobacteria as a Potential Source of Anticancer Compounds
Published in Gokare A. Ravishankar, Ranga Rao Ambati, Handbook of Algal Technologies and Phytochemicals, 2019
Polyketides are a diverse class of compounds that are synthesized through a series of modular enzymes that condense and then modify chains of acetate or propionate units via reduction, dehydration, cyclization and aromatization reactions (Tidgewell et al. 2010). A polyketide isolated from the marine cyanobacterium Trichodemium thiebautii, trichophycin A, was found to exhibit cytotoxic activity against neuro-2a neuroblastoma cell line (EC50=6.5 µM) and human colon cancer cell line HCT-116 (EC50=11.7 µM) (Bertin et al. 2017). The cytotoxicity of the compound could be related to its polyol character. In another study, nuiapolide isolated from Okeaniaplumata was found to display antichemotactic activity against Jurkat cells as well as slowing or blocking the G2/M phase of the cancerous cells (Mori et al. 2015). Another polyketide, polycavernoside D, isolated from Okeania sp, showed moderate activity against the H-460 human lung carcinoma cell line (Navarro et al. 2015). Andrianasolo et al. (2005) isolated another polyketide, swinholide A, from Symploca cf. sp collected from Fiji; and two related glycosylated derivatives, ankaraholides A and B, from Geitlerinema sp. collected from Madagascar. The swinholide-based compounds showed potent inhibition against cancer cell growth and exerted their cytotoxic effect by disrupting actin cytoskeleton. Teruya et al. (2009) tested biselyngbyaside, a macrolide glycoside isolated from Lyngbya sp., and found that it displayed broad-spectrum cytotoxicity in a human tumor cell line panel consisting of 39 cancer cell lines. The compound showed potent antiproliferative activity against the central nervous system cancer SNB-78 (GI50= 0.036 μM) and lung cancer NCI H522 (GI50 = 0.067 μM) cell lines.
Cytogenotoxic evaluation of the acetonitrile extract, citrinin and dicitrinin-A from Penicillium citrinum
Published in Drug and Chemical Toxicology, 2022
José Williams Gomes de Oliveira Filho, Teresinha de Jesus Aguiar dos Santos Andrade, Rosália Maria Tôrres de Lima, Dulce Helena Siqueira Silva, Antonielly Campinho dos Reis, José Victor de Oliveira Santos, Ag-Anne Pereira Melo de Meneses, Ricardo Melo de Carvalho, Ana Maria Oliveira da Mata, Marcus Vinícius Oliveira Barros de Alencar, Ana Carolina Soares Dias, Felipe Cavalcanti Carneiro da Silva, Muhammad Torequl Islam, Cain C. T. Clark, João Marcelo de Castro e Sousa, Ana Amélia de Carvalho Melo-Cavalcante
Polyketides are evident to induce apoptosis and MN formation (Yu et al.2006, Chan 2007, Dönmez-Altuntas et al.2007). CIT induces DNA damage via ROS formation through mitogen-activated protein kinase (MAPK) activation (Chan et al.2007, Farrugia and Balzan 2012). In rats, CIT at high doses was seen to increase mRNA expression for Ccna2, Ccnb1 and E2f1 transcription factors, leading to cell cycle modifications, CA and genotoxicity (Liu et al.2003, Knasmüller et al.2004, Bouslimi et al.2008, Folkmann et al.2009, Chang et al.2011, Kuroda et al.2013). In addition, the induction of MN, mediated by CIT, and several other damages caused to DNA were observed in HepG2 cells (Knasmüller et al.2004). A good candidate for an antitumor agent should have the ability to induce cytotoxic, genotoxic and mutagenic effects in neoplastic cells, generating blocking effects of the neoplastic process. CIT is capable of causing clastogenic effects in in vivo and in vitro test systems (Liu et al.2017).
Recent advances and future perspectives in the pharmacological treatment of Candida auris infections
Published in Expert Review of Clinical Pharmacology, 2021
Daniele R. Giacobbe, Laura Magnasco, Chiara Sepulcri, Malgorzata Mikulska, Philipp Koehler, Oliver A. Cornely, Matteo Bassetti
Turbinmicin was discovered through the screening of 1482 actinobacteria from marine invertebrates and subsequent challenge in vitro for activity against C. albicans. Turbinmicin was isolated from a sea squirt microbiome constituent, Micromonospora spp., and belongs to highly oxidized type II polyketides [112]. Its antifungal activity was tested against 39 fungi, including one isolate of fluconazole-resistant and micafungin-resistant C. auris, showing a MIC of 0.25 mg/L [112]. Turbinmicin was also evaluated in a neutropenic murine model of C. auris bloodstream infection, showing a greater reduction in fungal load in comparison with micafungin. Sec14p, a transfer protein essential for cellular trafficking, was identified as the antifungal target of turbinmicin [112].
Anti-inflammatory effect of 3,7-dimethyl-1,8-hydroxy-6-methoxyisochroman via nuclear factor erythroid 2-like 2-mediated heme oxygenase-1 expression in lipopolysaccharide-stimulated RAW264.7 and BV2 cells
Published in Immunopharmacology and Immunotoxicology, 2019
Wonmin Ko, Tran Hong Quang, Jae Hak Sohn, Joung Han Yim, Dae Gill Kang, Ho Sub Lee, Youn-Chul Kim, Hyuncheol Oh
The ocean contains the largest group of natural resources. Marine-derived fungi possess numerous novel potential therapeutic agents; thus, for many years, studies of marine-derived fungi have revealed new secondary metabolites and their pharmacological activities [23,24]. Fungi of the genus Penicillium have been considered as a profitable source for bioactive compounds for a long time. Recently, studies on marine-derived secondary metabolites from the genus Penicillium are rapidly increasing [25], and these metabolites account for 22% of the natural marine-derived fungal products. The structures of these metabolites have been identified to belong to various chemical classes such as polyketides, nitrogen compounds, sterols, and terpenoids. In addition, a considerable number of these compounds possess bioactivities such as antimicrobial, antiviral, antioxidant, and anti-inflammatory [26,27].