Abstract
NC1175 (3-[3-(4-chlorophenyl)-2-propenoyl]-4-[2-(4- chlorophenyl)vinylene]-1-ethyl-4-piperidinol hydrochloride) is a novel thiol- blocking conjugated styryl ketone that exhibits activity against a wide spectrum of pathogenic fungi. Incubation of NC1175 with various concentrations of cysteine and glutathione eliminated its antifungal activity in a concentration-dependent fashion. Since NC1175 is a lipophilic compound that has the potential to interact with cytoplasmic membrane components, we examined its effect on the membrane-located proton-translocating ATPase (H+- ATPase) of yeast (Candida albicans, Candida krusei, Candida guilliermondii, Candida glabrata, and Saccharomyces cerevisiae) and Aspergillus (Aspergillus fumigatus, Aspergillus niger, Aspergillus flavus, and Aspergillus nidulans) species. The glucose-induced acidification of external medium due to H+- ATPase-mediated expulsion of intracellular protons by these fungi was measured in the presence of several concentrations of the drug. NC1175 (12.5 to 50 μM) inhibited acidification of external medium by Candida, Saccharomyces, and Aspergillus species in a concentration-dependent manner. Vanadate-inhibited hydrolysis of ATP by membrane fractions of C. albicans was completely inhibited by 50 μM NC1175, suggesting that the target of action of NC1175 in these fungi may include H+-ATPase.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2950-2959 |
| Number of pages | 10 |
| Journal | Antimicrobial Agents and Chemotherapy |
| Volume | 43 |
| Issue number | 12 |
| State | Published - Jan 1 1999 |
Fingerprint
ASJC Scopus subject areas
- Pharmacology (medical)
Cite this
Proton-pumping-ATPase-targeted antifungal activity of a novel conjugated styryl ketone. / Manavathu, Elias K.; Dimmock, Jonathan R.; Vashishtha, Sarvesh C.; Chandrasekar, Pranatharthi H.
In: Antimicrobial Agents and Chemotherapy, Vol. 43, No. 12, 01.01.1999, p. 2950-2959.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Proton-pumping-ATPase-targeted antifungal activity of a novel conjugated styryl ketone
AU - Manavathu, Elias K.
AU - Dimmock, Jonathan R.
AU - Vashishtha, Sarvesh C.
AU - Chandrasekar, Pranatharthi H.
PY - 1999/1/1
Y1 - 1999/1/1
N2 - NC1175 (3-[3-(4-chlorophenyl)-2-propenoyl]-4-[2-(4- chlorophenyl)vinylene]-1-ethyl-4-piperidinol hydrochloride) is a novel thiol- blocking conjugated styryl ketone that exhibits activity against a wide spectrum of pathogenic fungi. Incubation of NC1175 with various concentrations of cysteine and glutathione eliminated its antifungal activity in a concentration-dependent fashion. Since NC1175 is a lipophilic compound that has the potential to interact with cytoplasmic membrane components, we examined its effect on the membrane-located proton-translocating ATPase (H+- ATPase) of yeast (Candida albicans, Candida krusei, Candida guilliermondii, Candida glabrata, and Saccharomyces cerevisiae) and Aspergillus (Aspergillus fumigatus, Aspergillus niger, Aspergillus flavus, and Aspergillus nidulans) species. The glucose-induced acidification of external medium due to H+- ATPase-mediated expulsion of intracellular protons by these fungi was measured in the presence of several concentrations of the drug. NC1175 (12.5 to 50 μM) inhibited acidification of external medium by Candida, Saccharomyces, and Aspergillus species in a concentration-dependent manner. Vanadate-inhibited hydrolysis of ATP by membrane fractions of C. albicans was completely inhibited by 50 μM NC1175, suggesting that the target of action of NC1175 in these fungi may include H+-ATPase.
AB - NC1175 (3-[3-(4-chlorophenyl)-2-propenoyl]-4-[2-(4- chlorophenyl)vinylene]-1-ethyl-4-piperidinol hydrochloride) is a novel thiol- blocking conjugated styryl ketone that exhibits activity against a wide spectrum of pathogenic fungi. Incubation of NC1175 with various concentrations of cysteine and glutathione eliminated its antifungal activity in a concentration-dependent fashion. Since NC1175 is a lipophilic compound that has the potential to interact with cytoplasmic membrane components, we examined its effect on the membrane-located proton-translocating ATPase (H+- ATPase) of yeast (Candida albicans, Candida krusei, Candida guilliermondii, Candida glabrata, and Saccharomyces cerevisiae) and Aspergillus (Aspergillus fumigatus, Aspergillus niger, Aspergillus flavus, and Aspergillus nidulans) species. The glucose-induced acidification of external medium due to H+- ATPase-mediated expulsion of intracellular protons by these fungi was measured in the presence of several concentrations of the drug. NC1175 (12.5 to 50 μM) inhibited acidification of external medium by Candida, Saccharomyces, and Aspergillus species in a concentration-dependent manner. Vanadate-inhibited hydrolysis of ATP by membrane fractions of C. albicans was completely inhibited by 50 μM NC1175, suggesting that the target of action of NC1175 in these fungi may include H+-ATPase.
UR - http://www.scopus.com/inward/record.url?scp=0032762173&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032762173&partnerID=8YFLogxK
M3 - Article
C2 - 10582888
AN - SCOPUS:0032762173
VL - 43
SP - 2950
EP - 2959
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
SN - 0066-4804
IS - 12
ER -