Reaction of anthramycin with DNA. Biological consequences of DNA damage in normal and xeroderma pigmentosum cell.

Petrusek, R.; Uhlenhopp, Elliott L.; DuTeau, Nancy M.; Hurley, Laurence H.

doi:10.1016/s0021-9258(20)65126-2

Cited by 63 publications

(16 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The conclusion in this paper that `trapping of the TC-NER complex stalled [during or] after DNA cleavage' is exactly in accord with our results and conclusions. This ¢nding is similar to that reported for phleomycin [47], anthramycin [25], and ditercalinium [48].…”

Section: Note Added In Proofsupporting

confidence: 90%

See 1 more Smart Citation

The inefficiency of incisions of ecteinascidin 743–DNA adducts by the UvrABC nuclease and the unique structural feature of the DNA adducts can be used to explain the repair-dependent toxicities of this antitumor agent

Zewail-Foote

Kohn

et al. 2001

Chemistry & Biology

View full text Add to dashboard Cite

The inefficient repair incision by the UvrABC nuclease of Et 743-DNA adducts provides a basis for rationalizing the observed repair-dependent cytotoxicities of these DNA adducts, if other associated structural properties of Et 743-DNA adducts are taken into account. In particular, the wedge-shaped Et 743, which forces open the minor groove of DNA, introducing a major groove bend, and the extrahelical protrusion of the C-subunit of Et 743 provide unique characteristics alongside the hydrogen-bonding stabilization of a covalent DNA adduct, which we propose traps an intermediate in NER processing of Et 743-DNA adducts. This trapped intermediate protein-Et 743-DNA adduct complex can be considered analogous to a poisoned topoisomerase I- or topoisomerase II-DNA complex. In the absence of an intact NER nuclease complex, this toxic lesion is unable to form, and the Et 743-DNA adducts, although not repaired by the NER pathway, are less toxic to cells. Conversely, elevated levels of either of these nucleases should lead to enhanced Et 743 toxicity.

show abstract

Section: Note Added In Proofsupporting

confidence: 90%

“…1B, only anthramycin has been tested for DNA repair. In this case, single-and double-strand breaks were found to be excision repair-dependent [25].…”

Section: Mutant Cell Lines De¢cient In the Transcriptionallymentioning

confidence: 72%

The inefficiency of incisions of ecteinascidin 743–DNA adducts by the UvrABC nuclease and the unique structural feature of the DNA adducts can be used to explain the repair-dependent toxicities of this antitumor agent

Zewail-Foote

Kohn

et al. 2001

Chemistry & Biology

View full text Add to dashboard Cite

show abstract

“…This natural product, produced by Streptomyces refuineus , possesses a cytotoxic activity by DNA alkylation. Indeed, anthramycin binds covalently with the exocyclic amino group (N 2 ) of guanine in the DNA minor groove, due to the presence of a reactive N10‐C11 carbinolamine function 283 . The induced DNA adduct causes only weak distortions of the helix, resulting in weak recognition and infrequent repair of these modifications 284 .…”

Section: Activity On Unknown Targetsmentioning

confidence: 99%

1,3‐Diazepine: A privileged scaffold in medicinal chemistry

Malki

Martinez

Masurier

2021

Medicinal Research Reviews

View full text Add to dashboard Cite

Privileged structures have been widely used as effective templates for drug discovery. While benzo‐1,4‐diazepine constitutes the first historical example of such a structure, the 1,3 analogue is just as rich in terms of applications in medicinal chemistry. The 1,3‐diazepine moiety is present in numerous biological active compounds including natural products, and is used to design compounds displaying a large range of biological activities. It is present in the clinically used anticancer compound pentostatin, in several recent FDA approved β‐lactamase inhibitors (e.g., avibactam) and also in coformycin, a natural product known as a ring‐expanded purine analogue displaying antiviral and anticancer activities. Several other 1,3‐diazepine containing compounds have entered into clinical trials. This heterocyclic structure has been and is still widely used in medicinal chemistry to design enzyme inhibitors, GPCR ligands, and so forth. This review endeavours to highlight the main use of the 1,3‐diazepine scaffold and its derivatives, and their applications in medicinal chemistry, drug design, and therapy. We will focus more particularly on the development of enzyme inhibitors incorporating this scaffold, with a strong emphasis on the molecular interactions involved in the inhibition mechanism.

show abstract

“…1 The imine or carbinolamine-containing pyrrolo [2,1c][1,4]benzodiazepines are a family of low molecular weight natural products originally isolated from Streptomyces species, 2 that are known to exhibit antitumour activity. These antibiotics bind selectively in the minor groove of DNA while a covalent aminal bond is formed between the electrophilic C11-position of the PBD and the nucleophilic N2-amino group of a guanine base, 3 resulting in biological activity. The S-configuration at the chiral C11a-position provides the PBD structure with the necessary right handed twist to fit snugly within the minor groove.…”

mentioning

confidence: 99%

Synthesis of DNA-Interactive Pyrrolo[2,1-c][1,4]benzodiazepines by Employing Polymer-Supported Reagents: Preparation of DC-81

Kamal¹,

Reddy²,

Devaiah³

et al. 2004

Synlett

View full text Add to dashboard Cite

Polymer-supported reagents have been utilized for the generation of combinatorial library of substituted pyrrolo[2,1c] [1,4]benzodiazepine derivatives that provides a clean and efficient preparation and does not require conventional purification techniques like chromatography. This methodology involves intra molecular aza-Wittig reaction and has been extended for the synthesis of the natural product DC-81 in good overall yields.

show abstract

Reaction of anthramycin with DNA. Biological consequences of DNA damage in normal and xeroderma pigmentosum cell.

Cited by 63 publications

References 24 publications

The inefficiency of incisions of ecteinascidin 743–DNA adducts by the UvrABC nuclease and the unique structural feature of the DNA adducts can be used to explain the repair-dependent toxicities of this antitumor agent

The inefficiency of incisions of ecteinascidin 743–DNA adducts by the UvrABC nuclease and the unique structural feature of the DNA adducts can be used to explain the repair-dependent toxicities of this antitumor agent

1,3‐Diazepine: A privileged scaffold in medicinal chemistry

Synthesis of DNA-Interactive Pyrrolo[2,1-c][1,4]benzodiazepines by Employing Polymer-Supported Reagents: Preparation of DC-81

Contact Info

Product

Resources

About