-
Experimental and Molecular Pathology Feb 1976
Comparative Study
Topics: Cytarabine; Deoxycytidine; Humans; Leukemia, Lymphoid; Lymphocytes; Mechlorethamine; Radiation Effects; Temperature
PubMed: 1253938
DOI: 10.1016/0014-4800(76)90059-9 -
Archives of Dermatology Dec 1984Seventy-six patients with mycosis fungoides (MF) were given topical mechlorethamine hydrochloride therapy. Allergic contact hypersensitivity reactions to the drug...
Seventy-six patients with mycosis fungoides (MF) were given topical mechlorethamine hydrochloride therapy. Allergic contact hypersensitivity reactions to the drug developed in 51 patients (67.1%). Sixty-four patients of the original 76 continued therapy, with 43 (67.2%) achieving a complete remission and 12 (18.8%) achieving a partial remission. Stage I disease responded significantly better than did subsequent, more severe disease stages. The median times to complete remission were 5.6 months, 32.3 months, and 22.3 months for stage I, II, and III disease, respectively. The conditions of patients with contact sensitivity did not respond better than those of patients without contact sensitivity. Patients with substage A disease did not respond better patients with substage B disease. These findings are encouraging and indicate that the use of topically applied mechlorethamine for early-stage MF should be continued, despite the development of contact dermatitis to the drug.
Topics: Administration, Topical; Adolescent; Adult; Aged; Child; Drug Hypersensitivity; Female; Humans; Hypersensitivity, Delayed; Male; Mechlorethamine; Middle Aged; Mycosis Fungoides; Skin Neoplasms; Time Factors
PubMed: 6508330
DOI: No ID Found -
Analytica Chimica Acta May 2008Previously, a method was presented for the analysis of mechlorethamine by derivatization of this unstable nitrogen mustard to bis(2-phenylthioethyl)methylamine (PTEMA),...
Previously, a method was presented for the analysis of mechlorethamine by derivatization of this unstable nitrogen mustard to bis(2-phenylthioethyl)methylamine (PTEMA), a stable compound suitable for analysis by HPLC with UV detection [J.C. Reepmeyer, J. Chromatogr. A, 1085 (2005) 262]. Mechlorethamine HCl served as a reference standard and it was derivatized in situ simultaneously with samples of mechlorethamine HCl in ointment preparations. This paper presents the synthesis of PTEMA on a gram scale, synthesis of its picrate salt, bis(2-phenylthioethyl)methylamine picrate (PTEMAP), and isolation of the picrate as a crystalline solid. PTEMAP may serve as a reference standard replacing the toxic mechlorethamine HCl. Insights into the handling, storage, drying, and hygroscopic properties of mechlorethamine HCl and PTEMAP are discussed. In addition, one step following the derivatization procedure in the original method is recognized as a potential for error, and a procedure relating to the order of addition of reagents is presented to avoid this error. The method has been extended to the analysis of mechlorethamine in aqueous solutions.
Topics: Chromatography, High Pressure Liquid; Diethylamines; Mechlorethamine; Molecular Structure; Sensitivity and Specificity; Solutions; Sulfides; Water
PubMed: 18471487
DOI: 10.1016/j.aca.2008.04.020 -
Chemical Research in Toxicology Jan 2014Oxidative stress plays a key role in mechlorethamine (methylbis(2-chloroethyl)amine, HN2) toxicity. The thioredoxin system, consisting of thioredoxin reductase (TrxR),...
Cross-linking of thioredoxin reductase by the sulfur mustard analogue mechlorethamine (methylbis(2-chloroethyl)amine) in human lung epithelial cells and rat lung: selective inhibition of disulfide reduction but not redox cycling.
Oxidative stress plays a key role in mechlorethamine (methylbis(2-chloroethyl)amine, HN2) toxicity. The thioredoxin system, consisting of thioredoxin reductase (TrxR), thioredoxin, and NADPH, is important in redox regulation and protection against oxidative stress. HN2 contains two electrophilic side chains that can react with nucleophilic sites in proteins, leading to changes in their structure and function. We report that HN2 inhibits the cytosolic (TrxR1) and mitochondrial (TrxR2) forms of TrxR in A549 lung epithelial cells. TrxR exists as homodimers under native conditions; monomers can be detected by denaturing and reducing SDS-PAGE followed by western blotting. HN2 treatment caused marked decreases in TrxR1 and TrxR2 monomers along with increases in dimers and oligomers under reducing conditions, indicating that HN2 cross-links TrxR. Cross-links were also observed in rat lung after HN2 treatment. Using purified TrxR1, NADPH reduced, but not oxidized, enzyme was inhibited and cross-linked by HN2. LC-MS/MS analysis of TrxR1 demonstrated that HN2 adducted cysteine- and selenocysteine-containing redox centers forming monoadducts, intramolecule and intermolecule cross-links, resulting in enzyme inhibition. HN2 cross-links two dimeric subunits through intermolecular binding to cysteine 59 in one subunit of the dimer and selenocysteine 498 in the other subunit, confirming the close proximity of the N- and C-terminal redox centers of adjacent subunits. Despite cross-linking and inhibition of TrxR activity by HN2, TrxR continued to mediate menadione redox cycling and generated reactive oxygen species. These data suggest that disruption of the thioredoxin system contributes to oxidative stress and tissue injury induced by HN2.
Topics: Animals; Cells, Cultured; Cross-Linking Reagents; Disulfides; Epithelial Cells; Humans; Lung; Male; Mechlorethamine; Models, Molecular; Oxidation-Reduction; Rats; Rats, Wistar; Thioredoxin-Disulfide Reductase
PubMed: 24274902
DOI: 10.1021/tx400329a -
Lancet (London, England) Aug 1980
Topics: Humans; Mechlorethamine; Mycosis Fungoides; Photochemotherapy
PubMed: 6105464
DOI: 10.1016/s0140-6736(80)90265-2 -
Bioorganic & Medicinal Chemistry Letters Jan 2015In this Letter, a new type of nitrogen mustard conjugate vesicles is developed to improve the stability and efficiency of anticancer drug. Benzoic acid nitrogen...
In this Letter, a new type of nitrogen mustard conjugate vesicles is developed to improve the stability and efficiency of anticancer drug. Benzoic acid nitrogen mustard-peptide (AAAK) conjugate was designed and synthesized, which was found to self-assemble into vesicles in water. The formation of the vesicles was confirmed by dynamic light scattering (DLS), transmission electron microscopy (TEM) and circular dichroism (CD). The degradation data revealed that the benzoic acid nitrogen mustard peptide (AAAK) conjugate vesicles are more stable than the parent drug in aqueous solution. Furthermore, MTT assay revealed that the free drug conjugate has similar antitumor activity against MCF-7, Hela, HepG-2 cell lines compared with the parent drug. The benzoic acid nitrogen mustard-peptide conjugate vesicles may have potential in the treatment of cancers.
Topics: Antineoplastic Agents; Benzoic Acid; Cell Survival; Dose-Response Relationship, Drug; Drug Carriers; HeLa Cells; Hep G2 Cells; Humans; MCF-7 Cells; Mechlorethamine
PubMed: 25515557
DOI: 10.1016/j.bmcl.2014.11.085 -
Annals of Internal Medicine Jul 1978
Topics: Humans; Mechlorethamine; Pleural Effusion
PubMed: 666162
DOI: 10.7326/0003-4819-89-1-139_2 -
Surgery Nov 1966
Topics: Animals; Bronchial Arteries; Catheterization; Dogs; Injections, Intra-Arterial; Lung; Mechlorethamine
PubMed: 5928100
DOI: No ID Found -
Journal of Materials Chemistry. B Mar 2023Nitrogen mustard (NM), a kind of alkylating agent similar to sulfur mustard, remains a threat to public health. However, there is nearly no satisfactory antidote for...
Nitrogen mustard (NM), a kind of alkylating agent similar to sulfur mustard, remains a threat to public health. However, there is nearly no satisfactory antidote for nitrogen mustard. Herein, we developed a supramolecular antidote to nitrogen mustard through efficient complexation of NM by carboxylatopillar[5]arene potassium salts (CP[5]AK). The cavity of methoxy pillar[5]arene (P5A) is sufficient to encapsulate NM with an association constant of 1.27 × 10 M, which was investigated by H NMR titration, density functional theory studies and independent gradient model studies. NM degrades to the reactive aziridinium salt (2) in the aqueous phase which irreversibly alkylates DNA and proteins, causing severe tissue damage. Considering the size/charge matching with toxic intermediate 2, water-soluble CP[5]AK was selected to encapsulate the toxic aziridinium salt (2), resulting in a high association constant of 4.10 × 10 M. The results of protection experiments of guanosine 5'-monophosphate (GMP) by CP[5]AK indicated that the formation of a complex could effectively inhibit the alkylation of DNA. Besides, and experiments also indicated that the toxicity of the aziridinium salt (2) is inhibited with the formation of a stable host-guest complex, and CP[5]AK has a good therapeutic effect on the damage caused by NM. This study provides a new mechanism and strategy for the treatment of NM exposure-induced skin injuries.
Topics: Mechlorethamine; Antidotes; DNA
PubMed: 36876404
DOI: 10.1039/d2tb02211g -
The Journal of Pharmacy and Pharmacology Jan 1993HPLC has been applied to determine the stability of mechlorethamine hydrochloride (nitrogen mustard) formulated as an ointment in white soft paraffin (10 mg drug, 50 g...
HPLC has been applied to determine the stability of mechlorethamine hydrochloride (nitrogen mustard) formulated as an ointment in white soft paraffin (10 mg drug, 50 g paraffin and 1 mL acetone). A new solubilization technique is described for extraction of the drug from the ointment for HPLC analysis which has an extraction efficiency of 76.1% with a coefficient of variation of 10.4%. Stored at 4 degrees C the drug content of the ointment remained stable for at least 84 days and stored at 37 degrees C the drug content remained stable for at least 40 days. In comparison aqueous solutions of mechlorethamine at the same concentration, fully degraded after 4 days. These data will aid hospital pharmacists decide on a standardized protocol for the controlled usage of the ointment which is both safe and cost-effective.
Topics: Chromatography, High Pressure Liquid; Drug Stability; Mechlorethamine; Ointment Bases; Ointments; Paraffin
PubMed: 8094449
DOI: 10.1111/j.2042-7158.1993.tb03669.x