Natural Polyketides to Prevent Cardiovascular Disease
Catherina Caballero-George in 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.
Transformation of Natural Products by Marine-Derived Microorganisms
Se-Kwon Kim in Marine Biochemistry, 2023
Polyketides are a class of natural products normally formed from the condensation of methylmalonyl-CoA, propanoyl-CoA and acetyl-CoA units by the action of polyketide synthase (PKS) enzymes. These compounds are found in plants, fungi, and bacteria (Hertweck, 2009; Dewick, 2009). The polyketides have relevant biological properties and are used as antibiotics, cholesterol reducers, antifungals, anti-tuberculosis agents, and antineoplastics (Dewick, 2009; Goswami et al., 2012; Lim et al., 2013; Jelić and Antolović, 2016).
Microalgae and Cyanobacteria as a Potential Source of Anticancer Compounds
Gokare A. Ravishankar, Ranga Rao Ambati in 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.
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].
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).
Inhibition of heterotrophic bacterial biofilm in the soil ferrosphere by Streptomyces spp. and Bacillus velezensis
Published in Biofouling, 2022
Nataliia Tkachuk, Liubov Zelena
Although antagonistic properties of S. canus strain NUChC F2 have not been observed, various strains of S. canus have been studied in the past and a number of compounds with antifungal and bactericidal activity have been identified (Zhang et al. 2013). In particular S. canus strain C-509 (ATCC 12647) was found to produce telomycin, an antibiotic with marked bactericidal activity (Hooper et al. 1962; Fu et al. 2015). S. canus strain IMCC 34906 was indicated among microorganisms with antimicrobial potential and isolated from Nepalese Soil (Khadayat et al. 2020). Liu et al. (2016) performed whole genome sequence of S. canus strain ATCC 12647. Twelve secondary metabolite biosynthetic gene clusters were identified, of which three were nonribosomal peptides, six were polyketides, one was another hybrid peptide-polyketide, and two were other metabolites. The complete nonribosomal peptide gene cluster responsible for the production of telomycin and its associated analogues was identified. Researchers also observed gene clusters with high homology scores corresponding to those known to produce coelichelin and albaflavenone. Other remaining nonribosomal peptide, polyketide, and hybrid clusters of substantial size are also present with yet-unknown identity (Liu et al. 2016).
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