Normaytansine, A New Antileukemic Ansa Macrolide From Maytenus buchananii

Sneden, Albert T.; Beemsterboer, George L.

doi:10.1021/np50011a019

Cited by 24 publications

(13 citation statements)

References 2 publications

(2 reference statements)

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“…59) Epimerisation at C10, e.g., in trewiasine to give 10- epitrewiasine, has little influence on the biological activity 58) and a hydroxy group at C15, as in colubrinol, is compatible with potent antitumor activity. 35,55) Neither the amide N-methyl group 60) nor the 20-O-methyl group 34) seem to be necessary for biological activity; in fact, 20-O-demethylansamitocin P3 is more active against P-388 and L-1210 leukemia in vivo than AP-3. 35) Surprisingly, the epoxide function also is not absolutely essential for antitumor activity, although it seems to modulate the activity.…”

Section: Structure-antitumor Activity Relationshipsmentioning

confidence: 99%

Recent Developments in the Maytansinoid Antitumor Agents

et al. 2004

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Section: Structure-antitumor Activity Relationshipsmentioning

confidence: 99%

Recent Developments in the Maytansinoid Antitumor Agents

et al. 2004

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“…Hydroxylation of C‐15 is compatible with potent antitumor activity 18, 19. Neither the amide 18‐ N ‐methyl group20 nor the 20‐ O ‐methyl group21 seems to be necessary for biological activity; in fact, 20‐ O ‐demethylansamitocin P‐3 was found to be more active than ansamitocin P‐3 against P‐338 and L‐1210 leukemia in vivo 18…”

Section: Introductionmentioning

confidence: 99%

Metabolism studies of the anti‐tumor agent maytansine and its analog ansamitocin P‐3 using liquid chromatography/tandem mass spectrometry

et al. 2005

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Maytansine, a potent clinically evaluated plant-derived anti-tumor drug, and its microbial counterpart, ansamitocin P-3, showed a substantially higher cytoxicity than many other anti-tumor drugs. Owing to a shortage of material and lack of sufficiently sensitive analytical methods at the time, no metabolism studies were apparently carried out in conjunction with the initial preclinical and clinical studies on maytansine, but some products of decomposition during the period of storage of the formulated drug were reported. In the current study, the in vitro metabolism of maytansine and ansamitocin P-3 was studied after incubation with rat and human liver microsomes in the presence of NADPH, and with rat and human plasma and whole blood, using liquid chromatography/multi-stage mass spectrometry. Unchanged ansamitocin P-3 and 11 metabolites and unchanged maytansine and seven metabolites were profiled and the structures of some metabolites were tentatively assigned based on their multi-stage electrospray ion-trap mass fragmentation data and in some cases accurate mass measurement. The major pathway of ansamitocin P-3 metabolism in human liver microsomes appears to be demethylation at C-10. Oxidation and sequential oxidation/demethylation also occurred, although to a lesser extent. However, the major pathway of maytansine metabolism in human liver microsomes is N-demethylation of the methylamide of the ester moiety. Several minor pathways including O/N-demethylation, oxidation and hydrolysis of the ester bond were also observed. There were no differences in maytansine metabolism between rat and human liver microsomes; however, the rate of metabolism of ansamitocin P-3 was different in rat and human liver microsomes. About 20% of ansamitocin P-3 was converted to its metabolites in rat liver microsomes and about 70% in human liver microsomes under the same conditions. Additionally, 10-O-demethylated ansamitocin P-3 was also detected in the urine after i.v. bolus administration of ansamitocin P-3 to Sprague-Dawley male rats. No metabolites were detected following incubation of maytansine and ansamitocin P-3 with human and rat whole blood and plasma.

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“…Compound 262 is an anti-tumor agent with a novel structure, and, therefore, is of great clinical interest. Subsequently, maytansine ( 262 ), maytanprine ( 263 ) and maytanbutine ( 264 ) were isolated from M. buchananii [ 89 ]. Larson et al [ 90 ] also isolated two new maytansinoid compounds, 2′- N -demethylmaytanbutine ( 265 ) and maytanbicyclinol ( 266 ) from M. buchananii ( Figure 7 ).…”

Section: Chemical Constituents Of Maytenusmentioning

confidence: 99%

A Review on Phytochemicals of the Genus Maytenus and Their Bioactive Studies

Huang

Chen

et al. 2021

Molecules

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The genus Maytenus is a member of the Celastraceae family, of which several species have long been used in traditional medicine. Between 1976 and 2021, nearly 270 new compounds have been isolated and elucidated from the genus Maytenus. Among these, maytansine and its homologues are extremely rare in nature. Owing to its unique skeleton and remarkable bioactivities, maytansine has attracted many synthetic endeavors in order to construct its core structure. In this paper, the current status of the past 45 years of research on Maytenus, with respect to its chemical and biological activities are discussed. The chemical research includes its structural classification into triterpenoids, sesquiterpenes and alkaloids, along with several chemical synthesis methods of maytansine or maytansine fragments. The biological activity research includes activities, such as anti-tumor, anti-bacterial and anti-inflammatory activities, as well as HIV inhibition, which can provide a theoretical basis for the better development and utilization of the Maytenus.

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Normaytansine, A New Antileukemic Ansa Macrolide From Maytenus buchananii

Cited by 24 publications

References 2 publications

Recent Developments in the Maytansinoid Antitumor Agents

Recent Developments in the Maytansinoid Antitumor Agents

Metabolism studies of the anti‐tumor agent maytansine and its analog ansamitocin P‐3 using liquid chromatography/tandem mass spectrometry

A Review on Phytochemicals of the Genus Maytenus and Their Bioactive Studies

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