Cispentacin, a new antifungal antibiotic. II. In vitro and in vivo antifungal activities.

Abstract

Cispentacin (( -)-(li?,2^)-2-aminocyclopentanel -carboxylic acid) is a new antifungal antibiotic possessing potent anii-Candida activity. The 50% inhibitory concentration (IC50) and IC100 values of cispentacin against clinical isolates of Candida albicans were in the ranges 6.3~12.5 and 6.3~50/jg/ml, respectively, by turbidimetric measurement in yeast nitrogen base glucose medium. No significant activity was seen against any yeasts and molds whentested by the agar dilution method using three different agar media; Knopp's agar, yeast extract -glucose -peptone agar and Sabouraud dextrose agar. This antibiotic demonstrated good therapeutic efficacy against a systemic Candida infection in mice by both parenteral and po administrations. The 50%protection dose (PD50) values after single iv and po administrations were 10 and 30 mg/kg, respectively. It was also effective in a systemic infection with Cryptococcus neoformans and in both lung and vaginal infections with C. albicans in mice. Cispentacin did not induce acute lethal toxicity at 1,000mg/kg by iv injection and 1,500mg/kg by ip and po administrations in mice.

Analogs of natural aminoacyl-tRNA synthetase inhibitors clear malaria in vivo

“…This phenomenon was observed even when mupirocin was removed from the culture after the first cycle of incubation. Cispentacin, a proline analog that inhibits prolyl-tRNA synthetase, was found to be a weak inhibitor of Plasmodium cultures even though it was previously shown to effectively protect against systemic Candida albicans and Cryptococcus neoformans infections (35). This discrepancy could be due to the fact that, in fungi, cispentacin accumulates at high intracellular levels through an active transport mechanism (36) that might be missing in Plasmodium.…”

Efficient Heterogeneously Palladium‐Catalysed Heck Arylation of Acrolein Diethyl Acetal. Selective Synthesis of Cinnamaldehydes or 3‐Arylpropionic Esters

“…[32] On the other hand, 3-arylpropionic acids are common building blocks in organic synthesis and an important intermediates in the preparation of biologically active compounds such as in the synthesis of 3-amino-3-arylpropionic acids (TNF-a inhibitors, lactam antibodies etc.). [33][34][35][36][37][38][39][40] Therefore, their selective synthesis using simple methods from commercially available substrates represents an important industrial challenge since it generally requires several reaction steps. As mentioned previously, Zebovitch and Heck reported the formation of arylpropionic esters by arylation of acrolein acetal with aryl halides using the PdA C H T U N G T R E N N U N G (OAc) 2 /PA C H T U N G T R E N N U N G (o-Tol) 3 catalytic system, in the presence of NEt 3 as base, but mixtures were obtained.…”

Applications of Actinobacterial Fungicides in Agriculture and Medicine

“…Schwartz et al (1988) studied L-671, 329, a new antifungal agent from Streptomyces strain. Oki et al (1989) studied cispentacin, a new antifungal antibiotic and its in vitro and in vivo antifungal activities. Novel antifungal antibiotics, Maniwamycins A and B I and II and their structure were studied and reported Takahashi et al, 1989).…”