New nitrogen mustards structurally related to (?)-Carnitine

Faissat, Ludovic

doi:10.1016/s0968-0896(02)00458-3

Cited by 13 publications

(2 citation statements)

References 37 publications

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“…Mitochondria are energy factories of biological systems and play important roles in energy metabolism of various biochemical processes, − and they are also the executioners of programmed cell death (apoptosis). , Because mitochondria are crucial in executing apoptosis-mediated cell death and cancer cells have suppressed apoptosis, mitochondria-directed drugs designed to trigger apoptosis are likely to be promising treatment strategies for curbing cancer. To date, a number of strategies for the delivery of biologically active molecules to the mitochondria of live mammalian cells have been demonstrated; − For example, Murphy and Smith’s group have designed a series of triphenylphosphonium-modified molecules with excellent mitochondria targeting capability . On the other hand, Sheu et al covalently linked trimethylammonium into their choline ester antioxidants to target mitochondria .…”

Section: Introductionmentioning

confidence: 99%

Dual-Targeting Nanosystem for Enhancing Photodynamic Therapy Efficiency

Zeng

et al. 2015

ACS Appl. Mater. Interfaces

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Photodynamic therapy (PDT) has been recognized as a valuable treatment option for localized cancers. Herein, we demonstrate a cellular and subcellular targeted strategy to facilitate PDT efficacy. The PDT system was fabricated by incorporating a cationic porphyrin derivative (MitoTPP) onto the polyethylene glycol (PEG)-functionalized and folic acid-modified nanographene oxide (NGO). For this PDT system, NGO serves as the carrier for MitoTPP as well as the quencher for MitoTPP's fluorescence and singlet oxygen ((1)O2) generation. Attaching a hydrophobic cation to the photosensitizer ensures its release from NGO at lower pH values as well as its mitochondria-targeting capability. Laser confocal microscope experiments demonstrate that this dual-targeted nanosystem could preferably enter the cancer cells overexpressed with folate receptor, and release its cargo MitoTPP, which subsequently accumulates in mitochondria. Upon light irradiation, the released MitoTPP molecules generate singlet oxygen and cause oxidant damage to the mitochondria. Cell viability assays suggest that the dual-targeted nanohybrids exhibit much higher cytotoxicity toward the FR-positive cells.

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Section: Introductionmentioning

confidence: 99%

Dual-Targeting Nanosystem for Enhancing Photodynamic Therapy Efficiency

Zeng

et al. 2015

ACS Appl. Mater. Interfaces

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“…5 Previous studies have demonstrated versatile designs for N-mustard agents based on naphthalimide, 6,7 (L)-Carnitine, 8 steroid derivatives, 9,10 tallimustine, 11 tetrapyrrole, 12 aromatic structures 13 (including nitroaniline, 14 aminocinnamic acid 15 ), imidazole derivatives, 16 and distamycin. 17 Alkylating agents are the largest class of anticancer agents and are cell-cycle nonspecific drugs that form highly reactive electrophilic species.…”

Section: Introductionmentioning

confidence: 99%

Applying pattern recognition methods to analyze the molecular properties of a homologous series of nitrogen mustard agents

Bartzatt¹,

Donigan²

2006

AAPS PharmSciTech

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The purpose of this research was to analyze the pharmacological properties of a homologous series of nitrogen mustard (N-mustard) agents formed after inserting 1 to 9 methylene groups (-CH 2 -) between 2 -N(CH 2 CH 2 Cl) 2 groups. These compounds were shown to have significant correlations and associations in their properties after analysis by pattern recognition methods including hierarchical classification, cluster analysis, nonmetric multi-dimensional scaling (MDS), detrended correspondence analysis, K-means cluster analysis, discriminant analysis, and self-organizing tree algorithm (SOTA) analysis. Detrended correspondence analysis showed a linear-like association of the 9 homologs, and hierarchical classification showed that each homolog had great similarity to at least one other member of the series-as did cluster analysis using paired-group distance measure. Nonmetric multi-dimensional scaling was able to discriminate homologs 2 and 3 (by number of methylene groups) from homologs 4, 5, and 6 as a group, and from homologs 7, 8, and 9 as a group. Discriminant analysis, K-means cluster analysis, and hierarchical classification distinguished the high molecular weight homologs from low molecular weight homologs. As the number of methylene groups increased the aqueous solubility decreased, dermal permeation coefficient increased, Log P increased, molar volume increased, parachor increased, and index of refraction decreased. Application of pattern recognition methods discerned useful interrelationships within the homologous series that will determine specific and beneficial clinical applications for each homolog and methods of administration.

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The Barton‐McCombie Reaction

2012

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Deoxygenations of alcohols, i.e., processes that replace a hydroxyl group with hydrogen at a saturated carbon, find applications in both total synthesis and the systematic modifications of natural products. They may also be employed to introduce deuterium or tritium in a site‐specific manner. Reductive methods that involve ionic or highly polarized reagents or intermediates can be limited in their applicability: for example, competing reaction pathways including cationic rearrangements and anionic eliminations may be encountered in sterically hindered systems with substrates bearing heteroatoms close to the center undergoing reduction. As evidenced by developments over the last few decades, methods that involve the generation and direct quenching via hydrogen atom abstraction of the derived, carbon‐centered radical typically show the greatest tolerance for the presence of other functional groups and for variations in both the steric acid and the electronic environment in the vicinity of the center undergoing deoxygenation. Derivatization of the hydroxyl is a prerequisite, the determinant factors for efficient formation of the deoxygenated product lies in the ability of the combination of the substrate and reagents to induce homolysis of the C‐O bond coupled with the induction of homolysis to rapidly reduce a free radical by hydrogen donation, thereby propagating an efficient chain process. A high‐yielding way to realize this sequence was first described by Barton McCombie using the free‐radical chain reaction of O ‐thioacyl derivatives of secondary alcohols with tri‐ n ‐butylstannane. This chapter provides a detailed description and comparison of the combinations of substrates and reagents that will bring about these processes and provides a summary and evaluation of alternative deoxygenation methods. Mechanistic and stereochemical issues set out the scope and limitations of these processes with respect to both the thioacylation and reduction steps and exemplify some applications to both total synthesis and the modification of natural products.

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New nitrogen mustards structurally related to (?)-Carnitine

Cited by 13 publications

References 37 publications

Dual-Targeting Nanosystem for Enhancing Photodynamic Therapy Efficiency

Dual-Targeting Nanosystem for Enhancing Photodynamic Therapy Efficiency

Applying pattern recognition methods to analyze the molecular properties of a homologous series of nitrogen mustard agents

The Barton‐McCombie Reaction

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