Immunopharmacological studies of new 3-benzoyl-4-mercaptobutyric acid derivatives. II. Immunosuppressive effects.
A number of D-penicillamine (PA) derivatives (3-benzoyl-4-mercaptobutyric acids) with an acetylthio group on the gamma-position of the carboxylic acid were synthesized. Their immunological effects were examined and compared with PA and other immunosuppressors. PA derivatives suppressed adjuvant-induced arthritis in SD and Lewis rats, suppressed delayed-type hypersensitivity and IgE antibody response in mice, and prolonged the survival time of NZBXNZW F1 hybrid (BWF1) mice, as did immunosuppressors. In vitro, PA derivatives suppressed lymphocyte transformation and the proliferation of KB cells. 4-Acetylthio-3-[-4-(4-chlorophenyl)benzoyl]butyric acid was the most effective of the PA derivatives. Thus, these PA derivatives with an acetylthio group on the gamma-position of the carboxylic acid showed immunosuppressive effects and, furthermore, substitution of the halogen atom on the phenyl group increased immunosuppressive activities.
Takeshita
K
K
Research Center, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Fukazawa
I
I
Nakaike
S
S
Kameo
K
K
Tomisawa
K
K
Otomo
S
S
Aihara
H
H
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D000970:Antineoplastic Agents; D001169:Arthritis, Experimental / Q000188:drug therapy; D001565:Benzoates / Q000138:chemical synthesis / Q000494:pharmacology*; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007166:Immunosuppressive Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D007624:KB Cells; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D010396:Penicillamine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats
D000970:Antineoplastic Agents; D001565:Benzoates; D007166:Immunosuppressive Agents; D010396:Penicillamine