The synthesis of novel melphalan derivatives as potential antineoplastic agents

Morris, Angela; Atassi, Ghanem; Guilbaud, Nicolas; Cordi, Alex

doi:10.1016/s0223-5234(97)89087-3

Cited by 13 publications

(10 citation statements)

References 15 publications

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“…Coupling of chlorambucil gave 3 and the subsequent coupling of 2 produced 4 in high yield, Scheme . Prior to coupling the amino group of melphalan was protected as the N - tert -butyloxycarbonyl ( N -Boc) derivative by treatment with di- tert -butyl dicarbonate (Boc) 2 O . Convergent coupling of N -Boc melphalan to the ester 5 was found to be higher yielding than the linear approach.…”

Section: Resultsmentioning

confidence: 99%

Design and Synthesis of a Nitrogen Mustard Derivative Stabilized by Apo-neocarzinostatin

et al. 2004

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Neocarzinostatin (NCS) is an antitumor antibiotic comprising a 1:1 protein-chromophore complex and exhibits cytotoxic action through DNA cleavage via H-abstraction. Cytotoxic activity resides with the chromophore 1 alone, while the protein (apoNCS) protects and transports labile 1. The naphthoate portion (2) of NCS chromophore (1) is important for binding to apoNCS and DNA intercalation. In this paper we describe our attempts to use apoNCS to improve the hydrolytic stability of novel bifunctional DNA alkylating agents. The nitrogen mustards, melphalan and chlorambucil, were both conjugated to 2, and the biological activities of these conjugates were assessed. Chlorambucil did not benefit from conjugation. The melphalan conjugate (6) formed covalent DNA adducts at guanine bases and exhibited greater in vitro cytotoxic activity than unmodified melphalan. Fluorescence and NMR spectroscopy showed that 6 binds to apoNCS. Binding to apoNCS-protected 6 reduced the extent of hydrolysis of the conjugate. This novel approach demonstrates for the first time that an enediyne apo-protein can be used to improve the stability of substances that are of potential interest in cancer chemotherapy.

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Section: Resultsmentioning

confidence: 99%

Design and Synthesis of a Nitrogen Mustard Derivative Stabilized by Apo-neocarzinostatin

et al. 2004

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“…26 Analogously, this will organize the esters of Pes-OH-Pes (9) and the amides of Pad-OH-Pad (10) at the same vertical level and allow a good preorganization for the formation of hydrogen bonds. A 1,2-backbone moiety will place the esters of Pes-Pes-OH (13) and the amides of Pad-Pad-OH (14) on different vertical levels and the preorganization for hydrogen bonding is less optimal. Although Pes-Pes-OH (13) and Pad-Pad-OH (14) show a hydrogen bonding effect, it is less pronounced than in Pes-OH-Pes (9) or Pad-OH-Pad (10) as can be seen by the lowered melting temperatures (62 uC vs. 72 uC and 110 uC vs. 132 uC, respectively).…”

Section: Double-tail Surfactantsmentioning

confidence: 99%

“…12 The 1,3-diamido lipid Pad-OH-Pad (10) has already been reported previously and its low solubility has been mentioned several times. 9,[13][14][15] However, a concise study of this phenomenon has been missing until now.…”

Section: Introductionmentioning

confidence: 99%

Study of surfactant alcohols with various chemical moieties at the hydrophilic–hydrophobic interface

Zaffalon¹,

D’Anna²,

Hagemann³

2013

RSC Adv.

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The melting behavior, the solubility, and the influence of hydrogen bonds were analyzed for a series of single- and double-tailed surfactant alcohols. Various effects such as the presence of free amides or the intermolecular spacing were found to be important factors for increasing or decreasing the melting temperature of a surfactant. Furthermore, we present a model for the packing of diamido-lipids and study the temperature-dependence of the IR signals

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“…Melphalan and chlorambucil, two members of this family, are employed in various cancer treatments. 12) However, these alkylating agents have numerous drawbacks because of their high reactivity and the ability to kill cells at whole using stage, [13][14][15] both of which greatly hinder their benefits. In an attempt to address their weaknesses, one of the most effective methods is to design and synthesize novel compounds by introducing functional groups into the molecular structures of alkylating agents.…”

mentioning

confidence: 99%

Novel Melphalan and Chlorambucil Derivatives of 2,2,6,6-Tetramethyl-1-piperidinyloxy Radicals: Synthesis, Characterization, and Biological Evaluation <i>in Vitro</i>

Zhao

Meng

Yuan

et al. 2010

CHEMICAL & PHARMACEUTICAL BULLETIN

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The synthesis of novel melphalan derivatives as potential antineoplastic agents

Cited by 13 publications

References 15 publications

Design and Synthesis of a Nitrogen Mustard Derivative Stabilized by Apo-neocarzinostatin

Design and Synthesis of a Nitrogen Mustard Derivative Stabilized by Apo-neocarzinostatin

Study of surfactant alcohols with various chemical moieties at the hydrophilic–hydrophobic interface

Novel Melphalan and Chlorambucil Derivatives of 2,2,6,6-Tetramethyl-1-piperidinyloxy Radicals: Synthesis, Characterization, and Biological Evaluation <i>in Vitro</i>

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