Benzylideneindanones and benzylidenebenzosuberones

Relationship between structure, antimycotic activity and acute toxicity

Tahsin M. Al-Nakib, P. Perjési, Ramani Varghese, Mary Jane Meegan

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

A series of E-2-benzylidene-1-indanones and E-2-benzylidene-1-benzosuberones were synthesized to investigate their in vitro antifungal activity against 24 strains belonging to important human pathogenic yeasts, such as Cryptococcus neoformans, Candida spp. and Trichosporon cutaneum. These strains were shown to be resistant to miconazole and isoconazole. There was a diversity in response among the different strains. Many of the compounds tested were shown to have good activity and many had minimum inhibitory concentrations (MICs) of 6 μg/ml or lower against most of the strains. The standard systemic and topical commercial drugs also showed a great degree of diversity, exhibiting MICs that ranged from 6 to > 100 μg/ml against the same yeast strains. The in vivo toxicity of the synthesized compounds tested by an acute toxicity procedure in mice (MFI strain) and the in vitro activity in HeLa cells suggests that most of the active compounds were of lower toxicity, while only a few were of a toxicity similar to that of the least toxic commercial antifungal agent investigated in our animal and cell culture models (amphotericin B). The relatively low LD50 and good MIC values of most of our compounds in comparison to the least toxic and most active commercial agents tested (amphotericin B and haloprogin, respectively) justifies the testing of these synthetic agents for further development.

Original languageEnglish
Pages (from-to)14-21
Number of pages8
JournalMedical Principles and Practice
Volume6
Issue number1
Publication statusPublished - Jan 1997

Fingerprint

Microbial Sensitivity Tests
Poisons
Amphotericin B
Indans
Yeasts
Trichosporon
Miconazole
Cryptococcus neoformans
Antifungal Agents
Lethal Dose 50
HeLa Cells
Candida
Cell Culture Techniques
Pharmaceutical Preparations
In Vitro Techniques

Keywords

  • Acute toxicity
  • Antimycotic activity in vitro
  • E-2-Benzylidene-1-benzosuberones
  • E-2-Benzylidene-1-indanones

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Benzylideneindanones and benzylidenebenzosuberones : Relationship between structure, antimycotic activity and acute toxicity. / Al-Nakib, Tahsin M.; Perjési, P.; Varghese, Ramani; Meegan, Mary Jane.

In: Medical Principles and Practice, Vol. 6, No. 1, 01.1997, p. 14-21.

Research output: Contribution to journalArticle

@article{9cc0de178d9f4027a6bc42ce68098345,
title = "Benzylideneindanones and benzylidenebenzosuberones: Relationship between structure, antimycotic activity and acute toxicity",
abstract = "A series of E-2-benzylidene-1-indanones and E-2-benzylidene-1-benzosuberones were synthesized to investigate their in vitro antifungal activity against 24 strains belonging to important human pathogenic yeasts, such as Cryptococcus neoformans, Candida spp. and Trichosporon cutaneum. These strains were shown to be resistant to miconazole and isoconazole. There was a diversity in response among the different strains. Many of the compounds tested were shown to have good activity and many had minimum inhibitory concentrations (MICs) of 6 μg/ml or lower against most of the strains. The standard systemic and topical commercial drugs also showed a great degree of diversity, exhibiting MICs that ranged from 6 to > 100 μg/ml against the same yeast strains. The in vivo toxicity of the synthesized compounds tested by an acute toxicity procedure in mice (MFI strain) and the in vitro activity in HeLa cells suggests that most of the active compounds were of lower toxicity, while only a few were of a toxicity similar to that of the least toxic commercial antifungal agent investigated in our animal and cell culture models (amphotericin B). The relatively low LD50 and good MIC values of most of our compounds in comparison to the least toxic and most active commercial agents tested (amphotericin B and haloprogin, respectively) justifies the testing of these synthetic agents for further development.",
keywords = "Acute toxicity, Antimycotic activity in vitro, E-2-Benzylidene-1-benzosuberones, E-2-Benzylidene-1-indanones",
author = "Al-Nakib, {Tahsin M.} and P. Perj{\'e}si and Ramani Varghese and Meegan, {Mary Jane}",
year = "1997",
month = "1",
language = "English",
volume = "6",
pages = "14--21",
journal = "Medical Principles and Practice",
issn = "1011-7571",
publisher = "S. Karger AG",
number = "1",

}

TY - JOUR

T1 - Benzylideneindanones and benzylidenebenzosuberones

T2 - Relationship between structure, antimycotic activity and acute toxicity

AU - Al-Nakib, Tahsin M.

AU - Perjési, P.

AU - Varghese, Ramani

AU - Meegan, Mary Jane

PY - 1997/1

Y1 - 1997/1

N2 - A series of E-2-benzylidene-1-indanones and E-2-benzylidene-1-benzosuberones were synthesized to investigate their in vitro antifungal activity against 24 strains belonging to important human pathogenic yeasts, such as Cryptococcus neoformans, Candida spp. and Trichosporon cutaneum. These strains were shown to be resistant to miconazole and isoconazole. There was a diversity in response among the different strains. Many of the compounds tested were shown to have good activity and many had minimum inhibitory concentrations (MICs) of 6 μg/ml or lower against most of the strains. The standard systemic and topical commercial drugs also showed a great degree of diversity, exhibiting MICs that ranged from 6 to > 100 μg/ml against the same yeast strains. The in vivo toxicity of the synthesized compounds tested by an acute toxicity procedure in mice (MFI strain) and the in vitro activity in HeLa cells suggests that most of the active compounds were of lower toxicity, while only a few were of a toxicity similar to that of the least toxic commercial antifungal agent investigated in our animal and cell culture models (amphotericin B). The relatively low LD50 and good MIC values of most of our compounds in comparison to the least toxic and most active commercial agents tested (amphotericin B and haloprogin, respectively) justifies the testing of these synthetic agents for further development.

AB - A series of E-2-benzylidene-1-indanones and E-2-benzylidene-1-benzosuberones were synthesized to investigate their in vitro antifungal activity against 24 strains belonging to important human pathogenic yeasts, such as Cryptococcus neoformans, Candida spp. and Trichosporon cutaneum. These strains were shown to be resistant to miconazole and isoconazole. There was a diversity in response among the different strains. Many of the compounds tested were shown to have good activity and many had minimum inhibitory concentrations (MICs) of 6 μg/ml or lower against most of the strains. The standard systemic and topical commercial drugs also showed a great degree of diversity, exhibiting MICs that ranged from 6 to > 100 μg/ml against the same yeast strains. The in vivo toxicity of the synthesized compounds tested by an acute toxicity procedure in mice (MFI strain) and the in vitro activity in HeLa cells suggests that most of the active compounds were of lower toxicity, while only a few were of a toxicity similar to that of the least toxic commercial antifungal agent investigated in our animal and cell culture models (amphotericin B). The relatively low LD50 and good MIC values of most of our compounds in comparison to the least toxic and most active commercial agents tested (amphotericin B and haloprogin, respectively) justifies the testing of these synthetic agents for further development.

KW - Acute toxicity

KW - Antimycotic activity in vitro

KW - E-2-Benzylidene-1-benzosuberones

KW - E-2-Benzylidene-1-indanones

UR - http://www.scopus.com/inward/record.url?scp=0001895829&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0001895829&partnerID=8YFLogxK

M3 - Article

VL - 6

SP - 14

EP - 21

JO - Medical Principles and Practice

JF - Medical Principles and Practice

SN - 1011-7571

IS - 1

ER -