Proton-pumping-ATPase-targeted antifungal activity of a novel conjugated styryl ketone

Elias K. Manavathu, Jonathan R. Dimmock, Sarvesh C. Vashishtha, Pranatharthi H. Chandrasekar

Research output: Contribution to journalArticle

28 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)2950-2959
Number of pages10
JournalAntimicrobial Agents and Chemotherapy
Volume43
Issue number12
StatePublished - Jan 1 1999

Fingerprint

Ketones
Adenosine Triphosphatases
Protons
Proton-Translocating ATPases
Candida
Fungi
Aspergillus
Candida albicans
Candida glabrata
Aspergillus nidulans
Aspergillus flavus
Saccharomyces
Aspergillus fumigatus
Vanadates
Membranes
Aspergillus niger
Sulfhydryl Compounds
Glutathione
Cysteine
Saccharomyces cerevisiae

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Manavathu, E. K., Dimmock, J. R., Vashishtha, S. C., & Chandrasekar, P. H. (1999). Proton-pumping-ATPase-targeted antifungal activity of a novel conjugated styryl ketone. Antimicrobial Agents and Chemotherapy, 43(12), 2950-2959.

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 journalArticle

Manavathu, EK, Dimmock, JR, Vashishtha, SC & Chandrasekar, PH 1999, 'Proton-pumping-ATPase-targeted antifungal activity of a novel conjugated styryl ketone', Antimicrobial Agents and Chemotherapy, vol. 43, no. 12, pp. 2950-2959.
Manavathu EK, Dimmock JR, Vashishtha SC, Chandrasekar PH. Proton-pumping-ATPase-targeted antifungal activity of a novel conjugated styryl ketone. Antimicrobial Agents and Chemotherapy. 1999 Jan 1;43(12):2950-2959.
Manavathu, Elias K. ; Dimmock, Jonathan R. ; Vashishtha, Sarvesh C. ; Chandrasekar, Pranatharthi H. / Proton-pumping-ATPase-targeted antifungal activity of a novel conjugated styryl ketone. In: Antimicrobial Agents and Chemotherapy. 1999 ; Vol. 43, No. 12. pp. 2950-2959.
@article{655c727ac477430db637d80efc1e04b6,
title = "Proton-pumping-ATPase-targeted antifungal activity of a novel conjugated styryl ketone",
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.",
author = "Manavathu, {Elias K.} and Dimmock, {Jonathan R.} and Vashishtha, {Sarvesh C.} and Chandrasekar, {Pranatharthi H.}",
year = "1999",
month = "1",
day = "1",
language = "English (US)",
volume = "43",
pages = "2950--2959",
journal = "Antimicrobial Agents and Chemotherapy",
issn = "0066-4804",
publisher = "American Society for Microbiology",
number = "12",

}

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 -