Structure-Activity Relationships among Zygosporin Derivatives

Minato, Hitoshi; Katayama, Teruaki; Matsumoto, Makoto; Katagiri, Ken; Matsuura, S.; Sunagawa, Norio; Hori, Kenji; Harada, Minoru; Takeuchi, Mitsuo

doi:10.1248/cpb.21.2268

Cited by 30 publications

(29 citation statements)

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“…The relatively low host toxicity exhibited by cytochalasins B is favorable for obtaining significant in vivo preclinical activity against neoplastic growths. Antineoplastic activity is supported by this study, by our previous studies [ 16 , 21 ], and in the early experience of others in the use of cytochalasins in vivo [ 26 , 27 ].…”

Section: Discussionsupporting

confidence: 85%

Chemotherapy in vivo against M109 murine lung carcinoma with cytochalasin B by localized, systemic, and liposomal administration

et al. 2015

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Cytochalasin B is a potentially novel microfilament-directed chemotherapeutic agent that prevents actin polymerization, thereby inhibiting cytokinesis. Although cytochalasin B has been extensively studied in vitro, only limited data are available to assess its in vivo potential. Cytochalasin B was administered to Balb/c mice challenged i.d. with M109 murine lung carcinoma to determine whether the agent could affect an established i.d. tumor when the compound is administered s.c. in the region of the i.d. tumor, but not in direct contact with it. Cytochalasin B was also administered either i.p. or s.c. at a distant site or i.v. to determine whether it could affect the long-term development of an established i.d. tumor. Cytochalasin B was then liposome encapsulated to determine whether the maximum tolerated dose (MTD) of the compound could be increased, while reducing immunosuppression that we have previously characterized. Liposomal cytochalasin B was also administered to mice challenged i.d. with M109 lung carcinoma to assess its chemotherapeutic efficacy. The results can be summarized as follows: 1) cytochalasin B substantially delayed the growth of i.d. M109 tumor nodules, inhibited metastatic progression in surrounding tissues, and produced long-term cures in treated mice; 2) liposomal cytochalasin B increased the i.p. MTD by more than 3-fold, produced a different distribution in tissue concentrations, and displayed antitumor effects against M109 lung carcinoma similar to non-encapsulated cytochalasin B. These data show that cytochalasin B exploits unique chemotherapeutic mechanisms and is an effective antineoplastic agent in vivo in pre-clinical models, either in bolus form or after liposome encapsulation.

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Section: Discussionsupporting

confidence: 85%

Chemotherapy in vivo against M109 murine lung carcinoma with cytochalasin B by localized, systemic, and liposomal administration

et al. 2015

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“…62 Minato and co-workers investigated structure-activity relationships among several native and semisynthetic zygosporin derivatives and concluded that besides the intact macrocycle, the hydroxyl function at C-7 and the benzyl group at C-3 of the isoindolone moiety are important pharmacophores concerning cytotoxic activity. 63 Several years later, the structure-activity relations regarding the impact on cellular structures, lymphocyte capping and actin polymerization were summarized as follows: the isoindolone nucleus constitutes the most important structural feature; likewise, the macrocyclic ring is necessary to confer bioactivity, even though the size seems to be insignificant. Derivatives with an aromatic substituent at C-10 (i.e.…”

Section: Cytotoxic Properties and Potential As Anticancer Agentsmentioning

confidence: 99%

“…In 1973, Minato and co-workers reported the cytotoxicity of a broad range of cytochalasin D derivatives. 63 The aim of this investigation was to find a derivative with reduced skin-irritating effects compared to cytochalasin D, while retaining cytotoxicity. The only substance matching these criteria was cytochalasin C, which was prepared from cytochalasin D by palladium-catalyzed hydrogenation.…”

Section: Chemical Derivatization Of Cytochalasins and Structureactivi...mentioning

confidence: 99%

The chemistry and biology of cytochalasans

et al. 2010

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“…Prior to this study, Minato and coworkers investigated structureactivity relationships among several native and semisynthetic cytochalasin derivatives and concluded that besides the intact macrocycle, the hydroxyl function at C-7 and the benzyl group at C-3 of the isoindolone moiety are important pharmacophores concerning cytotoxic activity [5,23]. In our study, the cytotoxicity of the cytochalasins 1, 2, and 6-10 against K562, A549, Huh-7, H1975, MCF-7, U937, BGC823, HL60, Hela, and MOLT-4 cell lines was assayed with the CCK8 (DOjinDo) method [24].…”

Section: Resultsmentioning

confidence: 99%

Cytotoxic Cytochalasins from Marine-Derived Fungus Arthrinium arundinis

Wang

Zhang

et al. 2015

Planta Med

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Four new cytochalasins, arthriniumnins A-D (1-4), a new natural product, ketocytochalasin (5), as well as five known cytochalasin analogues (6-10) were isolated and identified from the fungus Arthrinium arundinis ZSDS1-F3 from the sponge Phakellia fusca. Their structures were elucidated by NMR spectroscopic and mass spectrometric analyses, as well as single crystal X-ray diffraction. Compounds 6 and 9 showed cytotoxicity against K562, A549, Huh-7, H1975, MCF-7, U937, BGC823, HL60, Hela, and MOLT-4 cell lines, with IC50 values ranging from 1.13 to 47.4 µM.

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Structure-Activity Relationships among Zygosporin Derivatives

Cited by 30 publications

References 0 publications

Chemotherapy in vivo against M109 murine lung carcinoma with cytochalasin B by localized, systemic, and liposomal administration

Chemotherapy in vivo against M109 murine lung carcinoma with cytochalasin B by localized, systemic, and liposomal administration

The chemistry and biology of cytochalasans

Cytotoxic Cytochalasins from Marine-Derived Fungus Arthrinium arundinis

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