Synthesis and cytostatic activity of enynes, enediynes and dienediynes linked to intercalators

Braña, Miguel F.; Morán, Marina; Vega, M. Jesús Pérez de; Pita-Romero, Isabel; Walker, Nigel

doi:10.1016/0040-4020(95)00510-f

Cited by 19 publications

(8 citation statements)

References 22 publications

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“…However, the presence of alkyne substitution at the 3-and 4-positions of the naphthalene ring was found to decrease the cytotoxic activity of these compounds. 13 The parent compound (ring unsubstituted) 3 has also been used successfully developed for anticancer treatment and derivatives of this structure have entered clinical trials. Compound 3a, benzisoquinolinedione, which is also known as Nafidimide, was also synthesised by Braña et al and was found to show considerable activity in a series of animal tumours both in vitro and in vivo.…”

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confidence: 99%

Recent advances in the development of 1,8-naphthalimide based DNA targeting binders, anticancer and fluorescent cellular imaging agents

et al. 2013

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The development of functional 1,8-naphthalimide derivatives as DNA targeting, anticancer and cellular imaging agents is a fast growing area and has resulted in several such derivatives entering into clinical trials.This review gives an overview of the many discoveries and the progression of the use of 1,8-naphthalimides as such agents and their applications to date; focusing mainly on mono-, bis-naphthalimide based structures, and their various derivatives (e.g. amines, polyamine conjugates, heterocyclic, oligonucleotide and peptide based, and those based on metal complexes). Their cytotoxicity, mode of action and cell-selectivity are discussed and compared. The rich photophysical properties of the naphthalimides (which are highly dependent on the nature and the substitution pattern of the aryl ring) make them prime candidates as probes as the changes in spectroscopic properties such as absorption, dichroism, and fluorescence can all be used to monitor their binding to biomolecules. This also makes them useful species for monitoring their uptake and location within cells without the use of co-staining. The photochemical properties of the compounds have also been exploited, for example, for photocleavage of nucleic acids and for the destruction of tumour cells.

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confidence: 99%

Recent advances in the development of 1,8-naphthalimide based DNA targeting binders, anticancer and fluorescent cellular imaging agents

et al. 2013

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“…To further enhance the cytotoxicity of these products, Braña et al synthesized a 5,6-disubstituted derivative with enediyne groups (66) (Fig. 5) [7]. This compound which was evaluated for in vitro cytotoxicity against the human colon carcinoma HT-29 cell line, revealed an IC 50 of 30 M [7].…”

Section: Monomeric Naphthalimides: Design Synthesis Cytotoxic Activmentioning

confidence: 97%

“…These compounds were tested for their in vitro cytotoxic activity against human cervical carcinoma HeLa and human nasopharynx carcinoma KB cell lines ( Table 1) [3]. Two of these compounds (5: mitonafide) and (7) revealed potent cytotoxicity in the range of 0.5-1 M ( Table 1). The acute in vivo toxicity (LD 50 ) of these compounds was found to be in the range 4.5-32.5mg/kg [3].…”

Section: Monomeric Naphthalimides: Design Synthesis Cytotoxic Activmentioning

confidence: 99%

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Naphthalimides and Azonafides as Promising Anti-Cancer Agents

Ingrassia¹,

Lefranc²,

Kiss³

et al. 2009

CMC

134

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Naphthalimides, a class of compounds which bind to DNA by intercalation, have shown high anti-cancer activity against a variety of murine and more notably human cancer cell lines. Azonafide derivatives are also potential anti-tumor agents which are structurally related to the naphthalimides. Derivatives of azonafide have shown enhanced activity against various cancer models, especially leukemias, breast cancer and melanoma. Naphthalimides in general and amonafide in particular, are most probably the agents which have been involved in the greatest number of clinical trials without ever acceding to the market because of dose-limiting toxicity. This statement also reflects the immense interest that oncologists have paid to this class of compounds with respect to their anti-cancer potential. While the first generation of naphthalimides were mainly topoisomerse II poisons, some new compounds display novel mechanism of action. In contrast to the most widely used topo II poisons, including etoposide, adriamycin and their analogues, which often induce multi-drug resistance, several naphthalimide-related compounds have been reported not to be affected by this phenomenon. Multi-disciplinary approaches including medicinal chemistry, early toxicology and DMPK, in vivo activity assessment in diverse preclinical models and in-depth mechanism of action deciphering, along with the lessons learnt from previous and currently ongoing clinical trials, have resulted in the generation of a number of novel promising naphthalimide derivatives. It is thus reasonable to expect that members of this class of compounds will reach the oncology market in the near future.

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“…In general, they are less potent than azonafide against tumor cells, indicating that the linear anthracene chromophore is preferred. During the course of research directed towards obtaining more active naphthalimide derivatives, compound 112 [36], where the naphthalimide chromophore has been linked to an enediyne system, was synthesized. However, the antitumor activity against HT-29 cell line was lower than the model amonafide and, therefore, further studies were not carried out.…”

Section: Other Mononaphthalimidesmentioning

confidence: 99%

Naphthalimides as Anticancer Agents: Synthesis and Biological Activity

Braña

Ramos

2001

CMCACA

255

168

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Naphthalimides are a class of compounds with high antitumor activity upon a variety of murine and human tumor cells. These compounds bind to DNA by intercalation of the chromophore and two of them, mitonafide and amonafide, were used in clinical trials. The therapeutic properties of these lead drugs were improved by designing bisintercalating agents. One of these, elinafide, showed intense in vitro and in vivo activity and is currently being used in clinical trials against solid tumors. In this paper, the history of elinafide is described.

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Synthesis and cytostatic activity of enynes, enediynes and dienediynes linked to intercalators

Cited by 19 publications

References 22 publications

Recent advances in the development of 1,8-naphthalimide based DNA targeting binders, anticancer and fluorescent cellular imaging agents

Recent advances in the development of 1,8-naphthalimide based DNA targeting binders, anticancer and fluorescent cellular imaging agents

Naphthalimides and Azonafides as Promising Anti-Cancer Agents

Naphthalimides as Anticancer Agents: Synthesis and Biological Activity

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