Novel Cytotoxic Thiodiketopiperazine Derivatives from a <i>Tilachlidium</i> sp.

Feng, Yunjiang; Blunt, John W.; Cole, and Anthony L. J.; Munro, Murray H. G.

doi:10.1021/np030326w

Cited by 54 publications

(56 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These compounds have been earlier reported from Tilachlidium sp. and were shown to possess potential cytotoxic activity against P388 leukemia cells [29]. Subsequently, compound 1 was prepared synthetically and was found having broad range of cytotoxic activity against several cancer cell lines [36].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Antimicrobial Potential of Thiodiketopiperazine Derivatives Produced by Phoma sp., an Endophyte of Glycyrrhiza glabra Linn.

et al. 2016

View full text Add to dashboard Cite

During the screening of endophytes obtained from Glycyrrhiza glabra Linn., the extract from a fungal culture designated as GG1F1 showed significant antimicrobial activity. The fungus was identified as a species of the genus Phoma and was most closely related to Phoma cucurbitacearum. The chemical investigation of the GG1F1 extract led to the isolation and characterization of two thiodiketopiperazine derivatives. Both the compounds inhibited the growth of several bacterial pathogens especially that of Staphylococcus aureus and Streptococcus pyogenes, with IC values of less than 10 μM. The compounds strongly inhibited biofilm formation in both the pathogens. In vitro time kill kinetics showed efficient bactericidal activity of these compounds. The compounds were found to act synergistically with streptomycin while producing varying effects in combination with ciprofloxacin and ampicillin. The compounds inhibited bacterial transcription/translation in vitro, and also inhibited staphyloxanthin production in S. aureus. Although similar in structure, they differed significantly in some of their properties, particularly the effect on the expression of pathogenecity related genes in S. aureus at sub-lethal concentrations. Keeping in view the antimicrobial potential of these compounds, it would be needful to scale up the production of these compounds through fermentation technology and further explore their potential as antibiotics using in vivo models.

show abstract

Section: Discussionmentioning

confidence: 99%

“…The compounds were characterized by the analyses of HRESIMS, NMR (1D and 2D spectroscopy), and their comparison with the known compounds [29]. (Fig.…”

Section: Characterization Of Secondary Metabolitesmentioning

confidence: 99%

Antimicrobial Potential of Thiodiketopiperazine Derivatives Produced by Phoma sp., an Endophyte of Glycyrrhiza glabra Linn.

et al. 2016

View full text Add to dashboard Cite

show abstract

“…(R)-Lipoic acid (179) and sulfoxide-lipoic acid (180) are present both in animals and in plant organisms. They are bound to amidic nitrogen in the pyruvate dehydrogenaseand 2-oxoglutarate dehydrogenase complex.…”

Section: Thiolanesmentioning

confidence: 99%

“…All the compounds showed potent cytotoxicity against cultured P388 leukemia cells with ID 50 values of 0.25, 2.18, and 0.56 µM, respectively [180]. The minor components, Sch 52900 (228) and Sch 52901 (229), were isolated from a fermentation broth of the fungus Gliocladium sp.…”

Section: Epipolythiodioxopiperazinesmentioning

confidence: 99%

Pharmacologically Active Sulfur-Containing Compounds

Řezanka¹,

Sobotka²,

Spížek³

et al. 2006

AIAMC

View full text Add to dashboard Cite

In addition to sulfur-containing compounds that form essential and indispensable constituents of all living cells, there is a plethora of less wide-spread sulfur-containing compounds with much less common and often unexpected properties, chemical structures and biological activities. Some of these compounds have long been known as efficient antibiotics. This review surveys these less known compounds with two and more sulfur atoms in their molecule. In particular, it deals with natural heterocyclic compounds isolated, e.g., from bacteria, fungi, lichens, plants, and animals but also from unusual and exotic sources such as sea invertebrates (coelenterates, sponges, tunicates, sea worms), etc. Compounds such as calicheamicins, thiazole-related compounds and epipolythiodioxopiperazines may serve as examples. Because of their vast variety, individual compounds are grouped according to their chemical structure (only compounds whose chemical structure has been identified are included). These compounds affect a huge array of organisms from microorganisms to man, and the pharmacological activities they exert range from antiviral, antibacterial, antifungal, insecticidal or antiprotozoan effects to regulation of gene expression, cytoskeleton disruption, immunomodulation, plant growth stimulation or inhibition, pro-or antioxidant action, effects on selected enzymes, receptors and signal transduction pathways, etc. The activities are however often known only sketchily, and this paucity of data, and the fact that the activities were tested on a diverse spectrum of test organisms, cell lines, etc., is of necessity reflected in our survey. Two seemingly trivial but important points deserve attention: (a) compounds with widely different structures and from widely different sources have often very similar pharmacological effects; (b) a slight modification in the molecule may bring vast changes in the biological effects of the compound, in terms of quality, quantity and targeting. The purpose of the review was to show both the unique and common features of these compounds and to point out their potential usefulness for mankind.

show abstract

“…1a–b Indeed, the chemical ablation of the sulfur bridge in naturally occurring alkaloids ( e.g ., chaetocin A ( 4 ), 13f gliotoxin ( 1 ) 15 , sporidesmin 16 ) or the synthesis of analogs devoid of sulfur at the α-positions of the cyclo -dipeptide 17a results in biologically inactive compounds. Similarly, reductive S -methylation of the epidithiodiketopiperazine motif in a number of natural products ( e.g ., gliotoxin ( 1 ), 1b,5c,n,8a chaetocin A ( 4 ), 18 scabrosin, 19 sporidesmin, 16,20 T988 B, 21 bionectin C ( 8 ), 4 and chetracin D 22 ) unfailingly results in a dramatic loss of biological activity. Furthermore, a general pattern between the degree of sulfuration and the intensity of the biological response has not been clearly established.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and anticancer activity of epipolythiodiketopiperazine alkaloids

et al. 2013

View full text Add to dashboard Cite

The epipolythiodiketopiperazine (ETP) alkaloids are a highly complex class of natural products with potent anticancer activity. Herein, we report the application of a flexible and scalable synthesis, allowing the construction of dozens of ETP derivatives. The evaluation of these compounds against cancer cell lines in culture allows for the first expansive structure–activity relationship (SAR) to be defined for monomeric and dimeric ETP-containing natural products and their synthetic cognates. Many ETP derivatives demonstrate potent anticancer activity across a broad range of cancer cell lines, and kill cancer cellsviainduction of apoptosis. Several traits thatbode well for the translational potential of the ETP class of natural products includeconcise and efficient synthetic access, potent induction of apoptotic cell death, activity against a wide range of cancer types, and a broad tolerance for modifications at multiple sitesthat should facilitate small-molecule drug development, mechanistic studies, and evaluation in vivo.

show abstract

Novel Cytotoxic Thiodiketopiperazine Derivatives from a Tilachlidium sp.

Abstract: Three novel thiodiketopiperazine derivatives, T988 A, B, and C (1-3), were isolated from a Tilachlidium sp. Their structures were elucidated by spectroscopic analyses using various 1D and 2D NMR techniques. All the compounds showed potent cytotoxicity against cultured P388 leukemia cells.

Cited by 54 publications

References 10 publications

Antimicrobial Potential of Thiodiketopiperazine Derivatives Produced by Phoma sp., an Endophyte of Glycyrrhiza glabra Linn.

Antimicrobial Potential of Thiodiketopiperazine Derivatives Produced by Phoma sp., an Endophyte of Glycyrrhiza glabra Linn.

Pharmacologically Active Sulfur-Containing Compounds

Synthesis and anticancer activity of epipolythiodiketopiperazine alkaloids

Contact Info

Product

Resources

About