ABSTRACT
This paper describes the synthesis of new click-generated nitrogen mustards and their biological evaluation. By using the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction, we managed to synthesize eight new nitrogen mustards. This strategy paves the way for the synthesis of a new family of nitrogen mustard, with an important structural variability. Furthermore, we studied the biological activity of synthesized compounds by testing their cytotoxicity on four representative cancer cell lines A431, JURKAT, K562, and U266. One structure, 1-benzyl-4-(N,N-di-2-chloroethylaminomethyl)-1H-[1,2,3]triazole, showed an interesting cytotoxic effect.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Click Chemistry , Cytotoxins/chemical synthesis , Cytotoxins/pharmacology , Mechlorethamine/analogs & derivatives , Mechlorethamine/chemical synthesis , Neoplasms/drug therapy , Alkynes/chemistry , Azides/chemistry , Catalysis , Copper/chemistry , Cycloaddition Reaction , Humans , Mechlorethamine/pharmacology , Tumor Cells, CulturedABSTRACT
This paper deals with the synthesis of nitrogen mustard analogs, derivatives of purine bases. Alkylation in position N-9 and diethanolamine fixation on position 6 were managed by microwave irradiations. Chlorination of these dihydroxylated intermediates led to a cyclization, giving tricyclic purine base analogs bearing a chloroethyl chain. Finally, MTT assays on obtained compounds do not show cytotoxicity on four different cancer cell lines.
Subject(s)
Antineoplastic Agents, Alkylating/chemistry , Antineoplastic Agents, Alkylating/pharmacology , Mechlorethamine/analogs & derivatives , Mechlorethamine/pharmacology , Purines/chemistry , Purines/pharmacology , Alkylation , Antineoplastic Agents, Alkylating/chemical synthesis , Cell Line, Tumor , Cell Survival , Halogenation , Humans , Mechlorethamine/chemical synthesis , Neoplasms/drug therapy , Purines/chemical synthesisABSTRACT
This work deals with the synthesis of a new nitrogen mustard derivative based on thymine. To introduce the bis(2-chloroethyl)amine group to position 4 of the pyrimidine base, many strategies were explored and the desired compound was finally obtained, thanks to a synthetic pathway in five steps.
