Influence of conversion of penicillin G into a basic derivative on its accumulation and subcellular localization in cultured macrophages

Journal Article · Sun Mar 01 04:00:00 EST 1987 · Antimicrob. Agents Chemother.; (United States)

DOI:https://doi.org/10.1128/AAC.31.3.410· OSTI ID:6501297

Renard, C; Vanderhaeghe, H J; Claes, P J; Zenebergh, A; Tulkens, P M

beta-Lactam antibiotics do not accumulate in phagocytes, probably because of their acidic character. We therefore synthesized a basic derivative of penicillin G, namely, /sup 14/C-labeled N-(3-dimethylamino-propyl)benzylpenicillinamide (ABP), and studied its uptake and subcellular localization in J774 macrophages compared with that of /sup 14/C-labeled penicillin G. Whereas the intracellular concentration (Ci) of penicillin G remained lower than its extracellular concentration (Ce), ABP reached a Ci/Ce ratio of 4 to 5. Moreover, approximately 50% of intracellular ABP was found associated with lysosomes after isopycnic centrifugation of cell homogenates in isoosmotic Percoll or hyperosmotic sucrose gradients. The behavior of ABP was thus partly consistent with the model of de Duve et al., in which they described the intralysosomal accumulation of weak organic bases in lysosomes. Although ABP is microbiologically inactive, our results show that beta-lactam antibiotics can be driven into cells by appropriate modification. Further efforts therefore may be warranted in the design of active compounds or prodrugs that may prove useful in the chemotherapy of intracellular infections.

• Research Organization: Universite Catholique de Louvain, Brussels, Belgium
• OSTI ID: 6501297
• Journal Information: Antimicrob. Agents Chemother.; (United States), Journal Name: Antimicrob. Agents Chemother.; (United States) Vol. 3; ISSN AMACC
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANIMALS
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
BIOLOGICAL LOCALIZATION
CARBON 14 COMPOUNDS
CELL CONSTITUENTS
CELL CULTURES
CENTRIFUGATION
CONNECTIVE TISSUE CELLS
DRUGS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LYSOSOMES
MACROPHAGES
MAMMALS
MICE
ORGANOIDS
PENICILLIN
PHAGOCYTES
RODENTS
SEPARATION PROCESSES
SOMATIC CELLS
STRUCTURE-ACTIVITY RELATIONSHIPS
TRACER TECHNIQUES
ULTRACENTRIFUGATION
UPTAKE
VERTEBRATES