Preparation, characterization, and in vitro efficacy of O-carboxymethyl chitosan conjugate of melphalan

Lü, Bo; Huang, Dan; Zheng, Hua; Huang, Zhijun; Xu, Ping; Xu, Haixing; Yin, Yi; Liu, Xia; Li, Dan; Zhang, Xueqiong

doi:10.1016/j.carbpol.2013.04.071

Cited by 17 publications

(5 citation statements)

References 31 publications

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“…As early as the 1950s and 1960s, scientists worked with melphalan derivatives and studied their activity on cell lines and in animal models [8][9][10]. Today, this topic is still relevant, and various melphalan analogs are being evaluated that will be more effective than the parent drug [2,11,12]. Chemical modifications of the drug structure could serve as the basis for an improved chemotherapy system for MM patients.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and In Vitro Activity of Novel Melphalan Analogs in Hematological Malignancy Cells

Poczta

Krzeczyński

Tobiasz

et al. 2022

IJMS

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Despite the continuous developments in pharmacology and the high therapeutic effect of new treatment options for patients with hematological malignancies, these diseases remain a major health issue. Our study aimed to synthesize, analyze in silico, and determine the biological properties of new melphalan derivatives. We obtained three methyl esters of melphalan having in their structures amidine moieties substituted with thiomorpholine (EM–T–MEL), indoline (EM–I–MEL), or 4–(4–morpholinyl) piperidine (EM–MORPIP–MEL). These have not yet been described in the literature. The in vitro anticancer properties of the analogs were determined against THP1, HL60, and RPMI8226 cells. Melphalan derivatives were evaluated for cytotoxicity (resazurin viability assay), genotoxicity (alkaline comet assay), and their ability to induce apoptosis (Hoechst33342/propidium iodide double staining method; phosphatidylserine translocation; and caspase 3/7, 8, and 9 activity measurements). Changes in mitochondrial membrane potential were examined using the specific fluorescence probe JC–1 (5,5′,6,6′–tetrachloro–1,1′,3,3′–tetraethylbenzimidazol carbocyanine). The EM–T–MEL derivative had the highest biological activity, showing higher cytotoxic and genotoxic properties than the parent drug. Moreover, it showed a high ability to induce apoptosis in the tested cancer cells. This compound also had a beneficial effect in peripheral blood mononuclear cells (PBMC). In conclusion, we verified and confirmed the hypothesis that chemical modifications of the melphalan structure improved its anticancer properties. The conducted study allowed the selection of the compound with the highest biological activity and provided a basis for chemical structure–biological activity analyses.

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Section: Introductionmentioning

confidence: 99%

Synthesis and In Vitro Activity of Novel Melphalan Analogs in Hematological Malignancy Cells

Poczta

Krzeczyński

Tobiasz

et al. 2022

IJMS

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“…Chitosan can bind and disrupt the normal functions for the membrane of bacteria by promoting the leakage of intracellular components and inhibiting the transport of nutrients into the cells [9][10][11]. Previous works have focused on the effects of molecular weight and the degree of deacetylation of chitosan on some antibacterial and antifungal activities [12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Characterization, and Evaluation of Antimicrobial Activities of Chitosan and Carboxymethyl Chitosan Schiff-Base/Silver Nanoparticles

Khalil

Abdel-Monem

Darwesh

et al. 2017

Journal of Chemistry

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Schiff-bases of chitosan (CS) and carboxymethyl chitosan (CMCS)/silver nanoparticles (AgNPs) have been synthesized, characterized, and evaluated as antimicrobial agents against two Gram +ve bacteria (Bacillus cereus and Staphylococcus aureus) and two Gram −ve bacteria (Escherichia coli and Pseudomonas aeruginosa) in addition to Candida albicans as a fungus. The in situ reactions of CS and/or CMCS with some pyrazole aldehyde derivatives in acidic media containing silver nitrate to yield silver nanoparticles loaded onto CS and CMCS/Schiff-bases were carried out. Characterizations of the prepared compounds via FTIR spectroscopy, SEM, TEM, and TGA were carried out. Schiff-bases/silver nanoparticles of CS and CMCS showed higher antimicrobial activity than the blank CS and CMCS. The presence of AgNO3 (3% wt%) displayed high antibacterial efficiencies with inhibition zones in the extent of 19–39 mm. TEM analysis showed that the size of the silver nanoparticles is in the range of 4–28 nm for the prepared nanocomposites.

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“…To improve water solubility, systemic circulation time, and pharmacokinetic profiles, a research team led by Lu [ 129 ] synthesized and investigated a number of MEL-OCM-chitosan conjugates combined with various amino acid spacers (including glycine, l-phenylalanine, l-leucine, and 1-proline). OCM-chitosan shows no toxicity, high water solubility, biodegradability, and biocompatibility, and is thus one of the most useful candidate drug carriers.…”

Section: Attempts To Find a “Better Melphalan”mentioning

confidence: 99%

“…MEL-OCM-chitosan conjugates show satisfactory water solubility compared with free melphalan. In vitro studies show that conjugates are stable in plasma, although they are rapidly degraded in an enzyme solution [ 129 , 130 ].…”

Section: Attempts To Find a “Better Melphalan”mentioning

confidence: 99%

Treatment of Multiple Myeloma and the Role of Melphalan in the Era of Modern Therapies—Current Research and Clinical Approaches

Poczta

Rogalska

Marczak

2021

JCM

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Multiple myeloma (MM) accounts for 10% of all hematological malignancies, and it is the second most common hematological neoplasm for which chemotherapy is an important pharmacological treatment. High dose melphalan followed by autologous stem cell transplantation remains the standard of treatment for transplant-eligible patients with MM. In this review, we describe aspects of the pharmacokinetics and pharmacodynamics of melphalan therapy and related compounds. In addition, we describe the use of melphalan in innovative therapies for the treatment of MM, including the development of drug carriers to reduce systemic toxicity, combination therapy to improve the effectiveness of cancer therapy, and the chemical modification of the melphalan molecule to improve antitumor activity.

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Preparation, characterization, and in vitro efficacy of O-carboxymethyl chitosan conjugate of melphalan

Cited by 17 publications

References 31 publications

Synthesis and In Vitro Activity of Novel Melphalan Analogs in Hematological Malignancy Cells

Synthesis and In Vitro Activity of Novel Melphalan Analogs in Hematological Malignancy Cells

Synthesis, Characterization, and Evaluation of Antimicrobial Activities of Chitosan and Carboxymethyl Chitosan Schiff-Base/Silver Nanoparticles

Treatment of Multiple Myeloma and the Role of Melphalan in the Era of Modern Therapies—Current Research and Clinical Approaches

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