title: Synthesis and evaluation of antitumor activity of arylamides and cyclohexylamides of isomeric 3-chloro-4-(2-chloroethylthio)butanoic- and 4-chloro-3-(2-chloroethylthio)butanoic acids.
abstract: In the hope to find antitumor candidates among di-(2-chloroethyl)sulfides it was found that only 3-chloro-4-(2-chloroethylthio)butanoic (3-chloro) and 4-chloro-3-(2-chloroethylthio)butanoic (4-chloro) acids possess definite alkylating ability which is suggested to be a reason of their high antitumor activity. However, the clinical use of these agents is hampered by their high toxicity. A number of arylamides and cyclohexylamides of 3-chloro and 4-chloro acids were synthesized. A study of the toxicity and antitumor activity of synthesized derivatives in comparison with known 4-chloro-3-(2-chloroethylthio)butanoic acids shows that both 3-chloro and 4-chloro isomers possess high antitumor activity. Substitution of 3-chloro and 4-chloro butanoic acids by arylamides and cyclohexylamides residues R did not appear to increase the antitumor activity of the compounds. The presence of an anilide and cyclohexylamides carboxylic or alkylenecarboxylic substituent reduced the toxicity of the compounds 3-5 times in comparison with 3-chloro and 4-chloro anilides and cyclohexylamides. All synthesized compounds possess a broad spectrum of antitumor activity and are less toxic than the parent compound 4-chloro-3-(2-chloroethylthio)butanoic acid.
authors.affiliation: Institute of Biochemistry, Vilnius, Lithuania.
authors.forename: A
authors.initials: A
authors.lastname: Vektariene
authors.forename: A
authors.initials: A
authors.lastname: Palaima
authors.forename: V
authors.initials: V
authors.lastname: Simkeviciene
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D004354:Drug Screening Assays, Antitumor; D007536:Isomerism; D007928:Lethal Dose 50; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008815:Mice, Inbred Strains; D051381:Rats; D017208:Rats, Wistar; D014407:Tumor Cells, Cultured
chemical_list: D000577:Amides; D018906:Antineoplastic Agents, Alkylating