Isolation, purification, synthesis, and antiinvasive/antimetastatic activity of U-77863 AND U-77864 from Streptomyces griseoluteus, strain WS6724.

Harper, Don E.; Welch, Danny R.

doi:10.7164/antibiotics.45.1827

Cited by 15 publications

(7 citation statements)

References 9 publications

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“…Among them, compound 2 was previously found in a terrestrial Streptomycete GW 10/2517 ( Venugopal et al, 2002 ) and a marine-derived Streptomyces isolate B8112 ( Shaaban et al, 2011 ). o -Methylcinnamide (U-77863), the amide form of compound 3 , was reported in Streptomyces griseoluteus ( Harper and Welch, 1992 ). During our preparation of the manuscript, the compound with the same structure as globisporamic acid was isolated from Streptomyces sp.…”

Section: Resultsmentioning

confidence: 99%

Production of chain-extended cinnamoyl compounds by overexpressing two adjacent cluster-situated LuxR regulators in Streptomyces globisporus C-1027

Ren

et al. 2022

Front. Microbiol.

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Natural products from microorganisms are important sources for drug discovery. With the development of high-throughput sequencing technology and bioinformatics, a large amount of uncharacterized biosynthetic gene clusters (BGCs) in microorganisms have been found, which show the potential for novel natural product production. Nine BGCs containing PKS and/or NRPS in Streptomyces globisporus C-1027 were transcriptionally low/silent under the experimental fermentation conditions, and the products of these clusters are unknown. Thus, we tried to activate these BGCs to explore cryptic products of this strain. We constructed the cluster-situated regulator overexpressing strains which contained regulator gene(s) under the control of the constitutive promoter ermE*p in S. globisporus C-1027. Overexpression of regulators in cluster 26 resulted in significant transcriptional upregulation of biosynthetic genes. With the separation and identification of products from the overexpressing strain OELuxR1R2, three ortho-methyl phenyl alkenoic acids (compounds 1–3) were obtained. Gene disruption showed that compounds 1 and 2 were completely abolished in the mutant GlaEKO, but were hardly affected by deletion of the genes orf3 or echA in cluster 26. The type II PKS biosynthetic pathway of chain-extended cinnamoyl compounds was deduced by bioinformatics analysis. This study showed that overexpression of the two adjacent cluster-situated LuxR regulator(s) is an effective strategy to connect the orphan BGC to its products.

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Section: Resultsmentioning

confidence: 99%

Production of chain-extended cinnamoyl compounds by overexpressing two adjacent cluster-situated LuxR regulators in Streptomyces globisporus C-1027

Ren

et al. 2022

Front. Microbiol.

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“…The antimelanoma activity of molecules produced by Streptomyces griseoluteus was also evaluated using this approach. One of the tested molecules demonstrated a dose-dependent antimetastatic activity in vivo , however, none of them showed activity against solid melanoma tumor models in vivo (94). A liposome-based formulation of ET-18-OCH3 was also shown to be more effective in reducing lung tumor nodules in metastatic B16/F10 melanoma bearing mice than non-liposome-based formulations (97).…”

Section: Introductionmentioning

confidence: 99%

“…Although the B16 allogenic tumor model deserves special attention as it is the most widely used melanoma model for in vivo drug screening, other murine cells are also available to be inoculated into mice to form graft tumor models. These include K1735 and its subclone K1735-M2, both derived from C3H/HeN mice (86, 94), and the Cloudman S-9 cell line, obtained from the DBA/2 mouse (113, 125), in addition to a variety of other cell lines not addressed here.…”

Section: Introductionmentioning

confidence: 99%

“…In one study, TPI-1 analogs were tested, with analog TPI-1a4 found to inhibit growth of K1735 melanoma tumors in mice (86). In a screening of actinomycetes for substances with solid antitumor activity, a structure named U-77863 obtained from Streptomyces griseoluteus (strain WS6724) exhibited a dose-dependent antimetastatic activity in vivo in both K1735-M2 and B16-F10 murine melanoma models (94). Lastly, vitalethine was evaluated in mice inoculated with the uniformly fatal Cloudman S-91 melanoma cell line, displaying substantially diminished tumor sizes as well as increased survival (125).…”

Section: Introductionmentioning

confidence: 99%

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The Melding of Drug Screening Platforms for Melanoma

et al. 2019

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The global incidence of cancer is rising rapidly and continues to be one of the leading causes of death in the world. Melanoma deserves special attention since it represents one of the fastest growing types of cancer, with advanced metastatic forms presenting high mortality rates due to the development of drug resistance. The aim of this review is to evaluate how the screening of drugs and compounds for melanoma has been performed over the last seven decades. Thus, we performed literature searches to identify melanoma drug screening methods commonly used by research groups during this timeframe. In vitro and in vivo tests are essential for the development of new drugs; however, incorporation of in silico analyses increases the possibility of finding more suitable candidates for subsequent tests. In silico techniques, such as molecular docking, represent an important and necessary first step in the screening process. However, these techniques have not been widely used by research groups to date. Our research has shown that the vast majority of research groups still perform in vitro and in vivo tests, with emphasis on the use of in vitro enzymatic tests on melanoma cell lines such as SKMEL and in vivo tests using the B16 mouse model. We believe that the union of these three approaches ( in silico, in vitro , and in vivo ) is essential for improving the discovery and development of new molecules with potential antimelanoma action. This workflow would provide greater confidence and safety for preclinical trials, which will translate to more successful clinical trials and improve the translatability of new melanoma treatments into clinical practice while minimizing the unnecessary use of laboratory animals under the principles of the 3R's.

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“…150～152 ℃ (lit. [10] 151～153 ℃); 1 (E)-3-(间-甲苯基)丙烯酰胺(6b) [11] : 油状物, 产率 51.8%. 1 (E)-3-(2-甲氧苯基)丙烯酰胺(6d): 白色粉末, 产率 71.6%.…”

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Synthesis of (E)-N-(4-Styrene) Acrylamides for DNA Topoisomerase IIα Inhibitors and Antitumor Agents

Liu¹,

Li²,

Xiaoxia³

et al. 2022

Chinese Journal of Organic Chemistry

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研究论文 (E)-N-(4-苯乙烯基)丙烯酰胺类 DNA 拓扑异构酶 IIα 抑制剂的合成及抗肿瘤活性研究尹丽君 a 李超群 a 吴晓霞 a 徐广森 a 李志颖 a 沈月毛 * (山东大学药学院天然产物化学教育部重点实验室济南 250012) 摘要人 DNA 拓扑异构酶 IIα (topoisomerase IIα, Topo IIα)是重要的抗肿瘤药物靶标之一. 为发现新的高效、低毒 Topo IIα 抑制剂, 本研究通过对先导化合物 CL-2 进行骨架跃迁, 设计合成了 18 个(E)-N-(4-苯乙烯基)丙烯酰胺衍生物(A1～ A9, B1～B9). 18 个化合物对人三阴性乳腺癌 MDA-MB-231 细胞和人急性骨髓性白血病 KG1 细胞生长的抑制实验结果表明, (E)-N-(4-((E)-3,5-二羟基苯乙烯基)苯基)-3-(邻-甲苯基)丙烯酰胺(B1)和(E)-N-(4-((E)-3,5-二羟基苯乙烯基)苯基)-3-(4-硝基苯基)丙烯酰胺(B9)抑制 KG1 细胞生长的 IC50 分别为 0.43 和 0.5 μmol/L; (E)-N-(4-((E)-3,5-二羟基苯乙烯基) 苯基)-3-(2-羟基苯基)丙烯酰胺(B4)对 MDA-MB-231 细胞的生长抑制作用(IC50＝0.82 μmol/L)超过阳性对照 VP16 (IC50＝6.62 μmol/L). (E)-N-(4-((E)-3,5-二甲氧基苯乙烯基)苯基)-3-(邻-甲苯基)丙烯酰胺(A1)、B1、(E)-N-(4-((E)-3,5-二甲氧基苯乙烯基)苯基)-3-(2-甲氧苯基)丙烯酰胺(A4)、B4、(E)-N-(4-((E)-3,5-二甲氧基苯乙烯基)苯基)-3-(噻吩-3-基)丙烯酰胺(A9)和 B9 体外抑制 Topo IIα 介导的 DNA 松弛作用. 研究结果为发现新骨架 Topo IIα 抑制剂提供了新方向.

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Isolation, purification, synthesis, and antiinvasive/antimetastatic activity of U-77863 AND U-77864 from Streptomyces griseoluteus, strain WS6724.

Cited by 15 publications

References 9 publications

Production of chain-extended cinnamoyl compounds by overexpressing two adjacent cluster-situated LuxR regulators in Streptomyces globisporus C-1027

Production of chain-extended cinnamoyl compounds by overexpressing two adjacent cluster-situated LuxR regulators in Streptomyces globisporus C-1027

The Melding of Drug Screening Platforms for Melanoma

Synthesis of (E)-N-(4-Styrene) Acrylamides for DNA Topoisomerase IIα Inhibitors and Antitumor Agents

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