Chicamycin, a new antitumor antibiotic. I. Production, isolation and properties.

Konishi, Masataka; Hatori, Masami; Tomita, Koji; Sugawara, Masaru; Ikeda, Chiharu; Nishiyama, Yuta; Imanishi, Hideyo; Miyaki, Takeo; Kawaguchi, Hiroshi

doi:10.7164/antibiotics.37.191

Cited by 15 publications

(16 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The degree of unsaturation associated with the C-ring of a PBD can also influence its DNA-binding ability and cytotoxicity. In general, PBD monomers with C2-exo or C2endo unsaturation (e.g., anthramycin, [30] tomaymycin [46] and sibiromycin) [47] have enhanced DNA-binding affinity relative to PBD monomers with fully saturated C-rings (e.g., neothramycin A, [48] chicamycin [49] and DC-81). [1a] This feature has been adopted in the rational design of PBD dimers (see .…”

Section: C-ring Unsaturationmentioning

confidence: 99%

From Anthramycin to Pyrrolobenzodiazepine (PBD)‐Containing Antibody–Drug Conjugates (ADCs)

et al. 2016

View full text Add to dashboard Cite

The pyrrolo[2,1‐c][1,4]benzodiazepines (PBDs) are a family of sequence‐selective DNA minor‐groove binding agents that form a covalent aminal bond between their C11‐position and the C2‐NH2 groups of guanine bases. The first example of a PBD monomer, the natural product anthramycin, was discovered in the 1960s, and the best known PBD dimer, SJG‐136 (also known as SG2000, NSC 694501 or BN2629), was synthesized in the 1990s and has recently completed Phase II clinical trials in patients with leukaemia and ovarian cancer. More recently, PBD dimer analogues are being attached to tumor‐targeting antibodies to create antibody–drug conjugates (ADCs), a number of which are now in clinical trials, with many others in pre‐clinical development. This Review maps the development from anthramycin to the first PBD dimers, and then to PBD‐containing ADCs, and explores both structure–activity relationships (SARs) and the biology of PBDs, and the strategies for their use as payloads for ADCs.

show abstract

Section: C-ring Unsaturationmentioning

confidence: 99%

From Anthramycin to Pyrrolobenzodiazepine (PBD)‐Containing Antibody–Drug Conjugates (ADCs)

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Particularly indicative are the cases of chicamycin and porothramycin. The methoxy derivative of chicamycin was named chicamycin A, while the imine form of chicamycin was named chicamycin B . The methoxy derivative of porothramycin was named porothramycin B, while the carbinolamine form was named porothramycin A .…”

Section: Isolation and Characterization Of Naturally Produced Pyrrolomentioning

confidence: 99%

“…The methoxy derivative of chicamycin was named chicamycin A, while the imine form of chicamycin was named chicamycin B. 33 The methoxy derivative of porothramycin was named porothramycin B, while the carbinolamine form was named porothramycin A. 34 In most cases, the carbinolamine form is considered the parent compound, such as in mazethramycin, 35 sibiromycin, 36 and anthramycin.…”

Section: Isolation and Characterization Of Naturally Produced Pyrrolomentioning

confidence: 99%

Biosynthesis, synthesis, and biological activities of pyrrolobenzodiazepines

Gerratana

2010

Medicinal Research Reviews

118

143

View full text Add to dashboard Cite

Pyrrolobenzodiazepines (PBDs) are sequence selective DNA alkylating agents with remarkable antineoplastic activity. They are either naturally produced by actinomycetes or synthetically produced. The remarkable broad spectrum of activities of the naturally produced PBDs encouraged the synthesis of several PBDs, including dimeric and hybrid PBDs yielding to an improvement in the DNA binding sequence specificity and in the potency of this class of compounds. However, limitation in the chemical synthesis prevented the testing of one of the most potent PBDs, sibiromycin, a naturally produced glycosylated PBDs. Only recently the biosynthetic gene clusters for PBDs have been identified opening the doors to the production of glycosylated PBDs by mutasynthesis and biosynthetic engineering. The present review describes the recent studies on the biosynthesis of naturally produced pyrrolobenzodiazepines. In addition, it provides an overview on the isolation and characterization of naturally produced PBDs, on the chemical synthesis of PBDs, on the mechanism of DNA alkylation, and on the DNA binding affinity and cytotoxic properties of both naturally produced and synthetic pyrrolobenzodiazepines.

show abstract

“…Recently, there has been a considerable effort in the development of chemopreventive as well as chemotherapeutic agents from naturally occurring plant sources such as green tea, 3 resveratrol 4 , and grape seed proanthocyanidins 5 for the prevention and/or treatment of skin cancers. However, little attention has been given to the identification and isolation of natural compounds from microorganisms such as the chicamycin 6 and violacein 7 that possess the anti-tumor activity. Although violacein, which has been isolated from Chromobacterium violaceum, has gained some attention because of its antitumoral, antibacterial, antiulcerogenic, antileishmanial, and antiviral activities, 8,9 still little work has been done to elucidate the mechanism of action of this compound on diseased cells.…”

Section: Introductionmentioning

confidence: 99%

The antiproliferative function of violacein‐like purple violet pigment (PVP) from an Antarctic Janthinobacterium sp. Ant5‐2 in UV‐induced 2237 fibrosarcoma

Mojib¹,

Nasti²,

Andersen

et al. 2011

Int J Dermatology

View full text Add to dashboard Cite

Background In this study, we have investigated the chemotherapeutic potential of a purple violet pigment (PVP), which was isolated from a previously undescribed Antarctic Janthinobacterium sp. (Ant5-2), against murine UV-induced 2237 fibrosarcoma and B16F10 melanoma cells. Methods The 2237, B16F10, C50, and NIH3T3 cells were treated with PVP at different doses and for different times, and their proliferation and viability were detected by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Cell cycle arrest induced by PVP in 2237 fibrosarcoma cells was assessed by flow cytometry and expression analysis of cell cycle regulatory proteins were done by Western blot. Apoptosis induced by PVP in 2237 cells was observed by annexin-V/propidium iodide double staining flow cytometry assay and fluorescence microscopy. To further determine the molecular mechanism of apoptosis induced by PVP, the changes in expression of Bcl-2, Bax and cytochrome c were detected by Western blot. The loss of mitochondrial membrane potential in PVP treated 2237 cells was assessed by staining with JC-1 dye following flow cytometry. Caspase-3, Caspase-9 and PARP cleavage were analyzed by Western blot and Caspase-3 and -9 activities were measured by colorimetric assays. Results In vitro treatment of murine 2237 cells with the PVP resulted in decreased cell viability (13–79%) in a time (24–72 h) and dose (0.1–1 μM)-dependent manner. The PVP-induced growth inhibition in 2237 cells was associated with both G0/G1 and G2/M phase arrest accompanied with decrease in the expression of cyclin dependent kinases (Cdks) and simultaneous increase in the expression of cyclin dependent kinase inhibitors (Cdki) – Cip1/p21 and Kip1/p27. Further, we observed a significant increase in the apoptosis of the 2237 fibrosarcoma cells which was associated with an increased expression of pro-apoptotic protein Bax, decreased expression of anti-apoptotic proteins Bcl-2, disruption of mitochondrial membrane potential, cytochrome c release, activation of caspase-3, caspase-9 and poly-ADP-ribose-polymerase (PARP) cleavage. Conclusions We describe the anti-cancer mechanism of the PVP for the first time from an Antarctic bacterium and suggest that the PVP could be used as a potent chemotherapeutic agent against nonmelanoma skin cancers.

show abstract

Chicamycin, a new antitumor antibiotic. I. Production, isolation and properties.

Abstract: Chicamycin is a new antitumor antibiotic produced by a strain of Streptomyces albus, No. * This antibiotic was originally designated as BBM-2040 .

Cited by 15 publications

References 13 publications

From Anthramycin to Pyrrolobenzodiazepine (PBD)‐Containing Antibody–Drug Conjugates (ADCs)

From Anthramycin to Pyrrolobenzodiazepine (PBD)‐Containing Antibody–Drug Conjugates (ADCs)

Biosynthesis, synthesis, and biological activities of pyrrolobenzodiazepines

The antiproliferative function of violacein‐like purple violet pigment (PVP) from an Antarctic Janthinobacterium sp. Ant5‐2 in UV‐induced 2237 fibrosarcoma

Contact Info

Product

Resources

About