Verticillin A, a new antibiotic from Verticillium sp.

Minato, Hitoshi; Matsumoto, Mamoru; Katayama, Tsuyoshi

doi:10.1039/c29710000044

Cited by 36 publications

(31 citation statements)

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“…These include the neurokinin antagonists (+)-WIN64 821 (38) and (+)-WIN64 745 (39), both isolated from a strain of Aspergillus sp. ; [64][65][66] (À)-ditryptophenaline (40), obtained from Aspergillus flavus; [67] the antiviral agent (+)-asperdimin (41), isolated from extracts of Aspergillus niger; [68] chaetocin (42), isolated from the fermentation broth of Chaetomium minutum; [69] verticillins A (43), B, and C, obtained from Verticillium sp., exhibit antimicrobial activity against Gram-positive bacteria and potent antitumor activity in HeLa cell lines; [70][71][72] gliocladines A (44) and B (45); [24] 11,11'-dideoxyverticillin A and 11'-deoxyverticillin A; [24,73] melinacidins; [74][75][76] Sch52 900 and Sch52 901; [24] and some leptosins A (46), B (47), and C (48). [23] Leptosins C and F, isolated from the marine fungus Leptoshaeria sp., have inhibitory activity against topoisomerases I and II [77] (Scheme 2).…”

Section: Structure and Bioactivitymentioning

confidence: 99%

Structure, Bioactivity and Synthesis of Natural Products with Hexahydropyrrolo[2,3‐b]indole

Ruiz-Sanchis

Savina

Alberício

et al. 2011

Chemistry A European J

446

203

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Research on natural products containing hexahydropyrrolo[2,3-b]indole (HPI) has dramatically increased during the past few years. Newly discovered natural products with complex structures and important biological activities have recently been isolated and synthesized. This review summarizes the structures, biological activities, and synthetic routes for natural compounds containing HPI, emphasizing the different strategies for assembling this motif. It covers a broad range of molecules, from small alkaloids to complex peptides.

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Section: Structure and Bioactivitymentioning

confidence: 99%

Structure, Bioactivity and Synthesis of Natural Products with Hexahydropyrrolo[2,3‐b]indole

Ruiz-Sanchis

Savina

Alberício

et al. 2011

Chemistry A European J

446

203

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“…The first in this series, verticillin A, was isolated and characterized by Hitato and colleagues in the early 1970’s [12, 13]. The trivial name of this structural class was derived from the name of the fungus, Verticillium sp.…”

Section: Introductionmentioning

confidence: 99%

Plasma pharmacokinetics and bioavailability of verticillin A following different routes of administration in mice using liquid chromatography tandem mass spectrometry

Wang

Zhu

Kolli

et al. 2017

Journal of Pharmaceutical and Biomedical Analysis

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Verticillin A is a natural product isolated from fungal cultures and has displayed potent antibiotic, antiviral, nematocidal, and anticancer properties in vitro. While in vivo studies have been limited due to sparse supply, the in vivo efficacy data that does exist demonstrates potent anti-tumor activity in murine cancer models. The current study aims to investigate the pharmacokinetics and bioavailability of verticillin A in mice to provide guidance for further efficacy assessment in mouse models. A sensitive and specific liquid chromatography-tandem mass spectrometry method was developed and validated for the quantification of verticillin A in mouse plasma. Sample preparation was accomplished through protein precipitation, and chromatographic separation was achieved on an Agilent Zorbax Extend C18 column with a security guard cartridge C8 using a binary gradient with mobile phase A (water/0.1% formic acid) and B (ACN/0.1% formic acid) at a flow rate of 400 μl/min. Elution of verticillin A and internal standard, hesperetin, occurred at 4.87 and 2.06 min, respectively. The total chromatographic run time was 8 min., and the assay was linear in the concentration range of 1–1000 nM. The within- and between day precisions and accuracy were in the range of 2.58–8.71 and 90–105%, respectively. The assay was applied to determine plasma drug concentration in a mouse pharmacokinetic study. It was found that intraperitoneal dosing of 3 mg/kg resulted in high systemic exposure and achieved Cmax of 110 nM with plasma concentrations sustained above 10 nM for the 24-hour duration of the study. Intravenous and oral dosing achieved observed Cmax of 73 nM and 9 nM, respectively. Oral dosing resulted in an approximate 9% bioavailability. Comparing with previously published in vitro studies that demonstrated verticillin A is active in the 20 nM to 130 nM range, the pharmacokinetic data demonstrate similar levels are achieved in mouse plasma via intravenous or intraperitoneal dosing routes.

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“…Dimeric epipolythiodioxopiperazine (ETP) alkaloids are bioactive secondary metabolites reported to have potent cytotoxic 1–10 and antibacterial activities, 11–16 along with antiparasitic, 17 nematicidal, 18 antiviral, 19 and immunosuppressive properties. 20 This class of compounds has been isolated largely from several terrestrial and marine fungi, including species of the Leptosphaeria, Chaetomium, Tilachlidium, Verticillium, Gliocladium , and Penicillium genera.…”

Section: Introductionmentioning

confidence: 99%

Cytotoxic epipolythiodioxopiperazine alkaloids from filamentous fungi of the Bionectriaceae

et al. 2012

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Bioactivity-directed fractionation of the organic extracts of two filamentous fungi of the Bionectriaceae, strains MSX 64546 and MSX 59553 from the Mycosynthetix library, led to the isolation of a new dimeric epipolythiodioxopiperazine alkaloid, verticillin H (1), along with six related analogues, Sch 52900 (2), verticillin A (3), gliocladicillin C (4), Sch 52901 (5), 11′-deoxyverticillin A (6), and gliocladicillin A (7). The structures of compounds 1–7 were determined by extensive NMR and HRMS analyses, as well as by comparisons to the literature. All compounds (1–7) were evaluated for cytotoxicity against a panel of human cancer cell lines, displaying IC50 values ranging from 1.2 µM to 10 nM. Compounds 1–5 were examined for activity in the NF-κB assay, where compounds 2 and 3 revealed activity in the sub-micromolar range. Additionally, compounds 1, 3, and 4 were tested for EGFR inhibition using an enzymatic assay, while compound 3 was examined against an overexpressing EGFR+ve cancer cell line.

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Verticillin A, a new antibiotic from Verticillium sp.

Cited by 36 publications

References 0 publications

Structure, Bioactivity and Synthesis of Natural Products with Hexahydropyrrolo[2,3‐b]indole

Structure, Bioactivity and Synthesis of Natural Products with Hexahydropyrrolo[2,3‐b]indole

Plasma pharmacokinetics and bioavailability of verticillin A following different routes of administration in mice using liquid chromatography tandem mass spectrometry

Cytotoxic epipolythiodioxopiperazine alkaloids from filamentous fungi of the Bionectriaceae

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