Aplyronines D–H from the sea hare Aplysia kurodai: isolation, structures, and cytotoxicity

Ojika, Makoto; Kigoshi, Hideo; Suenaga, Kiyotake; Imamura, Yoshifumi; Yoshikawa, Kohji; Ishigaki, Takeshi; Sakakura, Akira; Mutou, Tsuyoshi; Yamada, Kiyoyuki

doi:10.1016/j.tet.2011.11.095

Cited by 21 publications

(26 citation statements)

References 17 publications

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“…Aplyronines A–H 3 (Figure 1) comprise a family of actin-binding marine macrolides that can serve as small molecule mimics of actin-binding proteins. They were isolated in low yield (10 –5 –10 –7 % based on wet weight) from the Japanese sea hare Aplysia kurodai by Yamada and co-workers based on their potent cytotoxicity against HeLa-S3 cells.…”

mentioning

confidence: 99%

Total Synthesis of Aplyronine C

et al. 2013

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A highly stereocontrolled total synthesis of the cytotoxic marine macrolide aplyronine C is described. The route exploits aldol methodology to install the requisite stereochemistry and features a crucial boron-mediated aldol coupling of an N-vinylformamide-bearing methyl ketone with a macrocyclic aldehyde to introduce the full side chain. The synthesis of two novel C21–C34 side chain analogs is also reported.

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confidence: 99%

Total Synthesis of Aplyronine C

et al. 2013

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“…By virtue of its highly potent antitumor properties, aplyronine D( 300,S cheme 15) [119] deserves serious consider-Scheme 10. Total synthesis of shishijimicinA(237).…”

Section: Aplyronine Dmentioning

confidence: 99%

The Role of Organic Synthesis in the Emergence and Development of Antibody–Drug Conjugates as Targeted Cancer Therapies

Nicolaou

Rigol

2019

Angew Chem Int Ed

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With a number of antibody–drug conjugates (ADCs) approved for clinical use as targeted cancer therapies and numerous candidates in clinical trials, the field of ADCs is emerging as one of the frontiers in biomedical research, particularly in the area of cancer treatment. Chemists, biologists and clinicians, among other scientists, are partnering their expertise to improve their design, synthesis, efficacy and precision as they strive to advance this paradigm of personalized and targeted medicine to treat cancer patients more effectively and to expand its scope to other indications. Just as Alexander Fleming's penicillin, and the myriad other bioactive natural products that followed its discovery and success in the clinic, ignited a revolution in medicine after the Second World War, so did calicheamicin γ1I, and other highly potent naturally occurring antitumor agents, play a pivotal role in enabling the advent of this new paradigm of “biological‐small molecule hybrid” medical intervention. Today there are four clinically approved drugs from the ADC paradigm, Mylotarg, Adcetris, Kadcyla and Besponsa, in order of approval, the first and the last of which carry the same calicheamicin γ1I‐derived payload. Covering oncological applications, and after a brief history of the emergence of the field of antibody–drug conjugates triggered more than a century ago by Paul Ehrlich's “magic bullet” concept, this Review is primarily focusing on the chemical synthesis aspects of the ADCs multidisciplinary research enterprise.

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“…The GI 50 values were 0.08, 0.5, 3, 10, and 22 nM for aplyronine D, A, B, H, and C, respectively, in the study by Ojika et al., who used human HeLa‐S3 cancer cells. Yamada et al .…”

Section: Mollusk‐derived Anticancer Agentsmentioning

confidence: 94%

“…found GI 50 values of ∼0.4 nM for aplyronine A, ∼4 nM for aplyronine B, and ∼20 nM for aplyronine C, respectively. The presence of various methylated amino acids ( N , N , O ‐trimethylserine or N , N ‐dimethylalanine) at the position 22 seems to influence the in vitro growth inhibitory activity of these macrolides . Aplyronine A is registered as NSC687160 in the NCI database and it displays the mean GI 50 value in the 60 cancer cell line panel of ∼0.2 nM.…”

Section: Mollusk‐derived Anticancer Agentsmentioning

confidence: 99%

Marine Mollusk‐Derived Agents with Antiproliferative Activity as Promising Anticancer Agents to Overcome Chemotherapy Resistance

Ciavatta

Lefranc

Carbone

et al. 2016

Medicinal Research Reviews

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The chemical investigation of marine mollusks has led to the isolation of a wide variety of bioactive metabolites, which evolved in marine organisms as favorable adaptations to survive in different environments. Most of them are derived from food sources, but they can be also biosynthesized de novo by the mollusks themselves, or produced by symbionts. Consequently, the isolated compounds cannot be strictly considered as “chemotaxonomic markers” for the different molluscan species. However, the chemical investigation of this phylum has provided many compounds of interest as potential anticancer drugs that assume particular importance in the light of the growing literature on cancer biology and chemotherapy. The current review highlights the diversity of chemical structures, mechanisms of action, and, most importantly, the potential of mollusk‐derived metabolites as anticancer agents, including those biosynthesized by mollusks and those of dietary origin. After the discussion of dolastatins and kahalalides, compounds previously studied in clinical trials, the review covers potentially promising anticancer agents, which are grouped based on their structural type and include terpenes, steroids, peptides, polyketides and nitrogen‐containing compounds. The “promise” of a mollusk‐derived natural product as an anticancer agent is evaluated on the basis of its ability to target biological characteristics of cancer cells responsible for poor treatment outcomes. These characteristics include high antiproliferative potency against cancer cells in vitro, preferential inhibition of the proliferation of cancer cells over normal ones, mechanism of action via nonapoptotic signaling pathways, circumvention of multidrug resistance phenotype, and high activity in vivo, among others. The review also includes sections on the targeted delivery of mollusk‐derived anticancer agents and solutions to their procurement in quantity.

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Aplyronines D–H from the sea hare Aplysia kurodai: isolation, structures, and cytotoxicity

Cited by 21 publications

References 17 publications

Total Synthesis of Aplyronine C

Total Synthesis of Aplyronine C

The Role of Organic Synthesis in the Emergence and Development of Antibody–Drug Conjugates as Targeted Cancer Therapies

Marine Mollusk‐Derived Agents with Antiproliferative Activity as Promising Anticancer Agents to Overcome Chemotherapy Resistance

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