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Anti-cancer Agents in Medicinal... 2022Cancer is considered one of the gruelling challenges and poses a grave health hazard across the globe. According to the International Agency for Research on Cancer... (Review)
Review
Cancer is considered one of the gruelling challenges and poses a grave health hazard across the globe. According to the International Agency for Research on Cancer (IARC), new cancer cases increased to 18.1 million in 2018, with 9.6 million deaths, bringing the global cancer rate to 23.6 million by 2030. In 1942, the discovery of nitrogen mustard as an alkylating agent was a tremendous breakthrough in cancer chemotherapy. It acts by binding to the DNA, and creating cross linkages between the two strands, leading to halt of DNA replication and eventual cell death. Nitrogen lone pairs of 'nitrogen mustard' produce an intermediate 'aziridinium ion' at the molecular level, which is very reactive towards DNA of tumour cells, resulting in multiple side effects with therapeutic consequences. Owing to its high reactivity and peripheral cytotoxicity, several improvements have been made with structural modifications for the past 75 years to enhance its efficacy and improve the direct transport of drugs to the tumour cells. Alkylating agents were among the first non-hormonal substances proven to be active against malignant cells and also the most valuable cytotoxic therapies available for the treatment of leukaemia and lymphoma patients. This review focus on the versatile use of alkylating agents and the Structure Activity Relationship (SAR) of each class of these compounds. This could provide an understanding for design and synthesis of new alkylating agents having enhanced target specificity and adequate bioavailability.
Topics: Alkylating Agents; Antineoplastic Agents; Antineoplastic Agents, Alkylating; DNA; Humans; Leukemia; Mechlorethamine; Neoplasms
PubMed: 34382529
DOI: 10.2174/1871520621666210811105344 -
The New England Journal of Medicine Dec 2012
Topics: Adolescent; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Child; Disease-Free Survival; Drugs, Generic; Hodgkin Disease; Humans; Mechlorethamine; Neoplasms; United States
PubMed: 23268661
DOI: 10.1056/NEJMp1212468 -
Archives of Dermatology Apr 1975Five patients with mycosis fungoides who had developed contact dermatitis to a nitrogen mustard, mechlorethamine hydrochloride, even in low concentrations (1 to 5 mg/100...
Five patients with mycosis fungoides who had developed contact dermatitis to a nitrogen mustard, mechlorethamine hydrochloride, even in low concentrations (1 to 5 mg/100 ml), received daily total-body applications of extremely dilute solutions (0.01 to 0.1 mg/100 ml) of mechlorethamine. The concentrations of the drug were approximately doubled weekly if the patient could tolerate it, or they were raised more slowly if the patient could not. Attempts to desensitize one patient were discontinued since he was unable to tolerate a greater concentration than 1.0 mg/100 ml after trying for one year. Another patient was able to tolerate a concentration of 3 mg/100 ml after three months, at which time his skin had completely cleared and treatment was stopped. Three other patients were desensitized during a period of 8 to 13 months to the point of tolerating the full therapeutic concentration used in our clinic (20 mg/100 ml) without experiencing dermatitis or pruritus.
Topics: Administration, Topical; Aged; Dermatitis, Contact; Desensitization, Immunologic; Humans; Male; Mechlorethamine; Middle Aged; Mycosis Fungoides
PubMed: 1122150
DOI: No ID Found -
The Journal of Steroid Biochemistry and... Sep 2013Nitrogen mustards, an important class of drugs for cancer therapy, are known as DNA alkylating agents. The nitrogen mustards are highly reactive and, as a consequence,... (Review)
Review
Nitrogen mustards, an important class of drugs for cancer therapy, are known as DNA alkylating agents. The nitrogen mustards are highly reactive and, as a consequence, lack of selectivity and produce several adverse side effects. In order to minimize these undesirable effects, the attachment of nitrogen mustards to a steroidal hormone with affinity for its receptor can lead to highly selective and less toxic antineoplastic therapeutics. This review will focus on the design, synthesis and evaluation of such steroid-nitrogen mustard hybrids as antineoplastic agents. Among these compounds, modified steroids with aromatic nitrogen mustards linked by an ester function were found to have better DNA alkylating properties, improved selectivity as well as low toxicity. This article is part of a Special Issue entitled "Synthesis and biological testing of steroid derivatives as inhibitors".
Topics: Antineoplastic Agents; Cell Line, Tumor; Humans; Mechlorethamine; Molecular Structure; Steroids
PubMed: 23692738
DOI: 10.1016/j.jsbmb.2013.05.004 -
Pediatric Nephrology (Berlin, Germany) Feb 1996
Topics: Alkylating Agents; Child; Drug Resistance; Humans; Mechlorethamine; Nephrosis, Lipoid; Nephrotic Syndrome
PubMed: 8611345
DOI: 10.1007/BF00863470 -
IARC Monographs on the Evaluation of... 1975
Review
Topics: Animals; Carcinogens; Drug Evaluation, Preclinical; Female; Humans; Lethal Dose 50; Male; Mechlorethamine; Mice; Neoplasms; Rats
PubMed: 791833
DOI: No ID Found -
Cancer Nursing Apr 1981
Topics: Mechlorethamine
PubMed: 6907056
DOI: No ID Found -
Archives of Dermatology Mar 1971
Topics: Dermatitis, Contact; Humans; Hydrochloric Acid; Male; Mechlorethamine; Psoriasis; Solutions
PubMed: 5548274
DOI: No ID Found -
Archives of Dermatology May 1972
Topics: Drug Hypersensitivity; Humans; Mechlorethamine; Microscopy, Electron; Psoriasis; Remission, Spontaneous; Skin; Skin Tests; Time Factors
PubMed: 5026678
DOI: No ID Found -
The Journal of Investigative Dermatology Nov 1975Progressive repigmentation occurred in vitiliginous skin of two patients topically treated with aqueous solutions of mechlorethamine. Hairless mice were found to provide...
Progressive repigmentation occurred in vitiliginous skin of two patients topically treated with aqueous solutions of mechlorethamine. Hairless mice were found to provide what seems to be a satisfactory cutaneous system for evaluating potential melanogenic properties of topically applied test compounds.
Topics: Administration, Topical; Aged; Animals; Female; Humans; Male; Mechlorethamine; Melanins; Mice; Mice, Inbred Strains; Middle Aged; Mycosis Fungoides; Skin Neoplasms; Skin Pigmentation; Vitiligo
PubMed: 1194712
DOI: 10.1111/1523-1747.ep12608217