NPI-2358 is a tubulin-depolymerizing agent: in-vitro evidence for activity as a tumor vascular-disrupting agent

Nicholson, Benjamin; Lloyd, G. Kenneth; Miller, Brian; Palladino, Michael A.; Kiso, Yoshiaki; Hayashi, Yoshio; Neuteboom, Saskia

doi:10.1097/01.cad.0000182745.01612.8a

Cited by 242 publications

(132 citation statements)

References 17 publications

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“…Structurally, halimide is composed of a phenylalanine, a histidine, and a tertiary butyl group. An analog of halimide, plinabulin (KPU-2, 79, Figure 16), that was obtained by molecular modification at the phenyl ring, has revealed a potent in vitro antitumor activity not only against various human tumor cell lines, but also against those with various MDR profiles [176]. Moreover, 79 was reported to have a similar mechanism of action to that of eribulin (31) as microtubule-disrupting agent with colchicine-like tubulin-depolymerizing activity, but the main problem concerning 79 is its poor solubility (<0.1 μM), which can trigger further studies on this scaffold.…”

Section: Halimide and Derivativesmentioning

confidence: 99%

Marine Natural Products as Models to Circumvent Multidrug Resistance

et al. 2016

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Multidrug resistance (MDR) to anticancer drugs is a serious health problem that in many cases leads to cancer treatment failure. The ATP binding cassette (ABC) transporter P-glycoprotein (P-gp), which leads to premature efflux of drugs from cancer cells, is often responsible for MDR. On the other hand, a strategy to search for modulators from natural products to overcome MDR had been in place during the last decades. However, Nature limits the amount of some natural products, which has led to the development of synthetic strategies to increase their availability. This review summarizes the research findings on marine natural products and derivatives, mainly alkaloids, polyoxygenated sterols, polyketides, terpenoids, diketopiperazines, and peptides, with P-gp inhibitory activity highlighting the established structure-activity relationships. The synthetic pathways for the total synthesis of the most promising members and analogs are also presented. It is expected that the data gathered during the last decades concerning their synthesis and MDR-inhibiting activities will help medicinal chemists develop potential drug candidates using marine natural products as models which can deliver new ABC transporter inhibitor scaffolds.

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Section: Halimide and Derivativesmentioning

confidence: 99%

Marine Natural Products as Models to Circumvent Multidrug Resistance

et al. 2016

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“…DKPs have long been disregarded; however, more recently they have received an increasing amount of attention in drug discovery (Krchnak et al, 1996). For both natural and synthetic DKPs, a wide variety of biological activities was reported, including antitumor (Milne et al, 1998;Nicholson et al, 2006), antiviral (Sinha et al, 2004), antifungal (Houston et al, 2004) and antibacterial (Kwon et al, 2000) activities.…”

Section: Discussionmentioning

confidence: 99%

Antimycobacterial activity of cyclic dipeptides isolated fromBacillussp. N strain associated with entomopathogenic nematode

Kumar

Mohandas

2013

Pharmaceutical Biology

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Context: Tuberculosis (TB) is one of the leading causes of morbidity and mortality with a global mortality rate of two million deaths per year; one-third of the world's population is infected with Mycobacterium tuberculosis. Objective: The aim of this study was to determine the antimycobacterial activity of six diketopiperazines (DKPs) purified from a Bacillus sp. N strain associated with entomopathogenic nematode Rhabditis (Oscheius) sp. Materials and methods: The minimum inhibitory concentration (MIC) and minimum bactericidal concentration of DKPs were determined using the broth dilution method on Middlebrook 7H11 against M. tuberculosis H 37 Rv. Time-kill assay was used to determine the rate of killing of M. tuberculosis H 37 Rv by DKPs. The cytotoxicity of the DKPs was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay against the VERO cell line. Results: Out of six DKP-tested cyclo-(D-Pro-L-Leu), cyclo-(L-Pro-L-Met) and cyclo-(D-Pro-L-Phe)recorded antimycobacterial activity, the cyclo-(L-Pro-L-Met) showed the highest activity and MIC values of 4 mg/ml for M. tuberculosis H 37 Rv. The MIC value for rifampicin was 0.06 mg/ml. Growth curve study by the MIC concentration of cyclic dipeptides recorded significant inhibition when compared with control. Time-kill curve showed maximum reduction of colony count was between 3 and 5 weeks. The DKPs are nontoxic to the VERO cell line up to 200 mg/ml. The antimycobacterial activity of cyclo-(D-Pro-L-Leu), cyclo-(L-Pro-L-Met) and cyclo-(D-Pro-L-Phe) is reported in this study for the first time. Discussion and conclusion: In conclusion, the potency, low cytotoxicity and selectivity of these compounds make them valid lead compounds for treatment against TB.

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“…Overall, 2,5-diketopiperazine derivatives emerged in the last decade as very attractive molecules in drug discovery [204][205][206][207][208][209][210]. Indeed, these derivatives usually exhibit various biological properties [211], including antitumor [212,213] antiviral [214], antifungal [215,216] antibacterial [217,218] or antifouling activities [219]. Interestingly, their role in the bitter taste of coffee, beer, cacao and chocolate has been highlighted [220].…”

Section: Piperazines Pyrazines and Oxazinesmentioning

confidence: 99%

Microwave-Assisted Synthesis of Bioactive Six-Membered Heterocycles and Their Fused Analogues

et al. 2016

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This review describes the formation of six-membered heterocyclic compounds and their fused analogues under microwave activation using modern organic transformations including cyclocondensation, cycloaddition, multicomponents and other modular reactions. The review is divided according to the main heterocycle types in order of increasing complexity, starting with heterocyclic systems containing one, two and three heteroatoms and their fused analogues. Recent microwave applications are reviewed, with special focus on the chemistry of bioactive compounds. Selected examples from the 2006 to 2015 literature are discussed.

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NPI-2358 is a tubulin-depolymerizing agent: in-vitro evidence for activity as a tumor vascular-disrupting agent

Cited by 242 publications

References 17 publications

Marine Natural Products as Models to Circumvent Multidrug Resistance

Marine Natural Products as Models to Circumvent Multidrug Resistance

Antimycobacterial activity of cyclic dipeptides isolated fromBacillussp. N strain associated with entomopathogenic nematode

Microwave-Assisted Synthesis of Bioactive Six-Membered Heterocycles and Their Fused Analogues

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