Identification of Pyrroloformamide as a Cytokinesis Modulator

Abreu, Paula Alvarez; Sousa, Thiciana S.; Jimenez, Paula Christine; Wilke, Diego Veras; Rocha, Danilo D.; Freitas, Hozana P. S.; Pessoa, Otília Deusdênia Loiola; Clair, James J. La; Costa-Lotufo, Letı́cia V.

doi:10.1002/cbic.201300717

Cited by 13 publications

(10 citation statements)

References 31 publications

(54 reference statements)

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“…Our research group has focused on the isolation of biologically relevant molecules from invertebrates from the Brazilian coast for the past 17 years 59 - 62 . Lately, to pursue sustainability and broaden the bioprospective regions, the group has begun to examine marine bacteria, including both free-living and invertebrate endophytes, for their anticancer potential 63 - 67 . Microorganism collection and isolation efforts from diverse matrixes and localities, ranging from the coast to remote islands, have led to a current in-house bank of over 1,000 bacterial strains.…”

Section: Introductionmentioning

confidence: 99%

Marine drugs for cancer: surfacing biotechnological innovations from the oceans

Jimenez¹,

Wilke²,

Costa-Lotufo³

2018

Clinics

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This review will discuss the contributions of marine natural molecules, a source only recently found to have pharmaceutical prospects, to the development of anticancer drugs. Of the seven clinically utilized compounds with a marine origin, four are used for the treatment of cancer. The development of these drugs has afforded valuable knowledge and crucial insights to meet the most common challenges in this endeavor, such as toxicity and supply. In this context, the development of these compounds will be discussed herein to illustrate, with successful examples provided by cytarabine, trabectedin, eribulin and brentuximab vedotin, the steps involved in this process as well as the scientific advances and technological innovation potential associated with developing a new drug from marine resources.

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Section: Introductionmentioning

confidence: 99%

Marine drugs for cancer: surfacing biotechnological innovations from the oceans

Jimenez¹,

Wilke²,

Costa-Lotufo³

2018

Clinics

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“…70 Bioactivity-guided fractionation of this strain yielded an orange crystalline compound, whose structure corresponds to that of VD844. As described in Section 2.2, VD844 was first isolated in 1969 as a potent antimicrobial.…”

Section: Mode Of Action and Self-resistancementioning

confidence: 95%

Dithiolopyrrolones: biosynthesis, synthesis, and activity of a unique class of disulfide-containing antibiotics

et al. 2014

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Dithiolopyrrolone (DTP) group antibiotics were first isolated in the early half of the 20th century, but only recently has research been reawakened by insights gained from the synthesis and biosynthesis of this structurally intriguing class of molecules. DTPs are characterized by an electronically unique bicyclic structure, which contains a compact disulfide bridge between two ene-thiols. Points of diversity within the compound class occur outside of the bicyclic core, at the two amide nitrogens. Such modifications distinguish three of the most well studied members of the class, holomycin, thiolutin, and aureothricin; the DTP core has also more recently been identified in the marine antibiotic thiomarinol, in which it is linked to a marinolic acid moiety, analog of the FDA-approved topical antibiotic Bactroban® (GlaxoSmithKline). Dithiolopyrrolones exhibit relatively broad-spectrum antibiotic activity against many Gram-positive and Gram-negative bacteria, as well as strains of Mycobacterium tuberculosis. Additionally, they have been shown to exhibit potent and selective anti-cancer activity. Despite this promising profile, there is still much unknown about the mechanisms of action for DTPs. Early reports suggested that they inhibit yeast growth at the level of transcription and that this effect is largely responsible for their distinctive microbial static properties; a similar mechanism is supported in bacteria. Elucidation of biosynthetic pathways for holomycin in Streptomyces clavuligerus and Yersinia ruckeri and thiomarinol in Alteromonas rava sp. nov. SANK 73390, have contributed evidence suggesting that multiple mechanisms may be operative in the activity of these compounds. This review will comprehensively cover the history and development of dithiolopyrrolones with particular emphasis on the biosynthesis, synthesis, biological activity and mechanism of action.

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“…Dithiolopyrrolones have been described as potent antibiotics against MRSA strains, most likely by targeting RNA polymerase 27. 30, 31 Although xenorhabdins might indeed function as antibiotics in the bacterium–nematode–insect relationship (killing other insect‐associated bacteria and thus food competitors), we thought that they might also target eukaryotic cells, as recently suggested for pyrroloformamide 32. Therefore, we tested 12 and 13 (as well as 9 ) against the causative agents of tropical diseases as well as for their cytotoxic effects against L6 (rat skeletal muscle) cells (Table 1).…”

Section: Resultsmentioning

confidence: 71%