Development of MBRI-001, a deuterium-substituted plinabulin derivative as a potent anti-cancer agent

Ding, Zhongpeng; Cheng, Hejuan; Wang, Shixiao; Hou, Yingwei; Zhao, Jianchun; Guan, Hongzai; Li, Wenbao

doi:10.1016/j.bmcl.2017.01.096

Cited by 17 publications

(10 citation statements)

References 23 publications

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“…Use of cesium carbonate as base for the condensation reaction is reported to give good yields. [61][62][63][64][65] This synthetic route is economically viable and possible to achieve high degree of chemically diverse dCDPs. The biological activity of many of the dCDPs are discussed (vide infra).…”

Section: Syntheses Of Dehydrocyclic Dipeptidesmentioning

confidence: 99%

Cyclic Dipeptide: A Privileged Molecular Scaffold to Derive Structural Diversity and Functional Utility

2021

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Cyclic dipeptides (CDPs) are the simplest form of cyclic peptides with a wide range of applications from therapeutics to biomaterials. CDP is a versatile molecular platform endowed with unique properties such as conformational rigidity, intermolecular interactions, structural diversification through chemical synthesis, bioavailability and biocompatibility. A variety of natural products with the CDP core exhibit anticancer, antifungal, antibacterial, and antiviral activities. The inherent bioactivities have inspired the development of synthetic analogues as drug candidates and drug delivery systems. CDP plays a crucial role as conformation and molecular assembly directing core in the design of molecular receptors, peptidomimetics and fabrication of functional material architectures. In recent years, CDP has rapidly become a privileged scaffold for the design of advanced drug candidates, drug delivery agents, bioimaging, and biomaterials to mitigate numerous disease conditions. This review describes the structural diversification and multifarious biomedical applications of the CDP scaffold, discusses challenges, and provides future directions for the emerging field.

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Section: Syntheses Of Dehydrocyclic Dipeptidesmentioning

confidence: 99%

Cyclic Dipeptide: A Privileged Molecular Scaffold to Derive Structural Diversity and Functional Utility

2021

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“…The Npropargyl-plinabulin derivatives 5 and 6 were synthesized from 1,4-diacetyl-2,5-piperazinedione 1 through 2 steps [1][2][3][4][5][6][7][8]11,17 (Schemes 1 and 2, Supplemental Figures S6-S13). The first was aldol condensation between aldehyde derivatives and 1,4-diacetyl-2,5-piperazinedione via K 2 CO 3 -catalysis and methylation with propargyl bromide in one-pot 4 to give the Npropargyl-piperidinedione derivatives 3 in high yield 91% (Supplemental Figures S1 and 2).…”

Section: Resultsmentioning

confidence: 99%

“…1 Historically, notable VDAs, such as colchicine and combretastatin, have been found to be effective anti-cancer drugs. 2 On the other hand, plinabulin has a relatively favorable safety profile while still exhibiting colchicine-like tubulin depolymerizing activity. Several plinabulin derivatives showed high cytotoxicity against different cancer cell lines, for example, benzophenone derivatives were evaluated against human HT-29 colorectal cancer cells, while 5-tertbutyl-substituted imidazole analogs were not highly active.…”

mentioning

confidence: 99%

Synthesis and Cytotoxic Activity of Several Novel N-Alkyl-Plinabulin Derivatives With Aryl Group Moieties

Tham¹,

Quynh²,

Tuyen³

et al. 2021

Natural Product Communications

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Seven novel N-alkyl-plinabulin derivatives with aryl groups moieties (nitroquinoline, 1,4-dihydroquinoline, 4-methoxybenzene, and 4-chlorobenzene) have been synthesized via aldol condensation and alkylation in one-pot, and tested for their cytotoxicity against 4 cancer cell lines (KB, HepG2, Lu, and MCF7). Compounds ( Z)−3-((6,8-dimethyl-4-oxo-1,4-dihydroquinolin-2-yl)methylene)−6-(( Z)−4-methoxybenzylidene)−1-(prop-2-yn-1-yl)piperazine-2,5-dione (5a), ( Z)−6-(( Z)−4-methoxybenzylidene)−1-(prop-2-yn-1-yl)−3-((1,6,8-trimethyl-4-oxo-1,4-dihydroquinolin-2-yl)methylene)piperazine-2,5-dione (5b), and ( Z)−3-(( Z)−4-chlorobenzylidene)−1,4-dimethyl-6-((8-methyl-4-nitroquinolin-2-yl)methylene)piperazine-2,5-dione (8) showed strong cytotoxicity against 3 of the cancer cells lines (KB, HepG2 and Lu) with IC50 values ranging from 3.04 to 10.62 µM. The quinoline-derived compounds had higher cytotoxic activity than the benzaldehyde derivatives. The successful synthesis of these derivatives offers useful information for the development of more potent vascular disrupting agents based on plinabulin.

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“…23 Plinabulin VII is in a world-wide Phase III clinical trial for non-small cell lung cancer. 24 Plinabulin blocks the polymerization of tubulin in a unique manner, resulting in multifactorial effects including an enhanced immune-oncology response, 25 activation of the JNK pathway and disruption of the tumor blood supply. 26 Indibulin VIII has shown promising anticancer activity with a minimal neurotoxicity in preclinical animal studies and in Phase I clinical trials for cancer chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

Design, eco-friendly synthesis, molecular modeling and anticancer evaluation of thiazol-5(4H)-ones as potential tubulin polymerization inhibitors targeting the colchicine binding site

et al. 2020

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Development of MBRI-001, a deuterium-substituted plinabulin derivative as a potent anti-cancer agent

Cited by 17 publications

References 23 publications

Cyclic Dipeptide: A Privileged Molecular Scaffold to Derive Structural Diversity and Functional Utility

Cyclic Dipeptide: A Privileged Molecular Scaffold to Derive Structural Diversity and Functional Utility

Synthesis and Cytotoxic Activity of Several Novel N-Alkyl-Plinabulin Derivatives With Aryl Group Moieties

Design, eco-friendly synthesis, molecular modeling and anticancer evaluation of thiazol-5(4H)-ones as potential tubulin polymerization inhibitors targeting the colchicine binding site

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