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Identification of alkaloid compounds arborinine and graveoline from Ruta angustifolia L. Pers for their antifungal potential against isocitrate lyase ICL1 gene of candida albicans

Candida albicans has been reported globally as the most widespread pathogenic species contributing candidiasis from superficial to systemic infections in immunocompromised individuals. Their metabolic adaptation depends on glyoxylate cycle to survive in nutrient-limited host. The long term usage of...

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Main Authors: Mohd Kamal, Laina Zarisa, Ahmed Adam, Mowaffaq Adam, Mohd Shahpudin, Siti Nurfatimah, Shuib, Ahmad Naqeeb, Sandai, Rosline, Mohd Hassan, Norazian, Tabana, Yasser M., Basri, Dayang Fredalina, Thian, Leslie Lung Than, Sandai, Doblin
Format: Article
Language:English
Published: Springer 2021
Online Access:http://psasir.upm.edu.my/id/eprint/97595/1/ABSTRACT.pdf
http://psasir.upm.edu.my/id/eprint/97595/
https://link.springer.com/article/10.1007/s11046-020-00523-z
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spelling my.upm.eprints.975952022-07-26T03:11:45Z http://psasir.upm.edu.my/id/eprint/97595/ Identification of alkaloid compounds arborinine and graveoline from Ruta angustifolia L. Pers for their antifungal potential against isocitrate lyase ICL1 gene of candida albicans Mohd Kamal, Laina Zarisa Ahmed Adam, Mowaffaq Adam Mohd Shahpudin, Siti Nurfatimah Shuib, Ahmad Naqeeb Sandai, Rosline Mohd Hassan, Norazian Tabana, Yasser M. Basri, Dayang Fredalina Thian, Leslie Lung Than Sandai, Doblin Candida albicans has been reported globally as the most widespread pathogenic species contributing candidiasis from superficial to systemic infections in immunocompromised individuals. Their metabolic adaptation depends on glyoxylate cycle to survive in nutrient-limited host. The long term usage of fungistatic drugs and the lack of cidal drugs frequently result in strains that could resist commonly used antifungals and display multidrug resistance (MDR). In search of potential therapeutic intervention and novel fungicidals, we have explored a plant alkaloids, namely arborinine and graveoline for its antifungal potential. Alkaloids belongs to Rutaceae family have been reported with numerous antimicrobial activities. In this study, we aimed to isolate and identify the antifungal active alkaloids of R. angustifolia and assess antifungal effect targeting C. albicans isocitrate lyase (ICL) gene which regulates isocitrate lyase, key enzyme in glyoxylate cycle contributing to the virulence potential of C. albicans. Alkaloids were extracted by bioassay guided isolation technique which further identified by TLC profile and compared with the standard through HPLC and NMR analysis. The antifungal activities of the extracted alkaloids were quantified by means of MIC (Minimum Inhibitory Concentration). The gene expression of the targeted gene upon treatment was analysed using RT-qPCR and western blot. Additionally, this study looked at the drug-likeness and potential toxicity effect of the active alkaloid compounds in silico analysis. Spectroscopic analysis showed that the isolated active alkaloids were characterized as acridone, furoquinoline, 4-quinolone known as arborinine and graveoline. Results showed that each compound significantly inhibited the growth of C. albicans at the dose of 250 to 500 µg/mL which confirm its antifungal activity. Each alkaloid was found to successfully downregulate the expression of both ICL1 gene CaIcl1 protein. Finally, ADMET analysis suggests a good prediction of chemical properties, namely absorption, distribution, metabolism, excretion and toxicity (ADMET) that will contribute in drug discovery and development later on. Springer 2021 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/97595/1/ABSTRACT.pdf Mohd Kamal, Laina Zarisa and Ahmed Adam, Mowaffaq Adam and Mohd Shahpudin, Siti Nurfatimah and Shuib, Ahmad Naqeeb and Sandai, Rosline and Mohd Hassan, Norazian and Tabana, Yasser M. and Basri, Dayang Fredalina and Thian, Leslie Lung Than and Sandai, Doblin (2021) Identification of alkaloid compounds arborinine and graveoline from Ruta angustifolia L. Pers for their antifungal potential against isocitrate lyase ICL1 gene of candida albicans. Mycopathologia, 186 (2). 221 - 236. ISSN 0301-486X; ESSN: 1573-0832 https://link.springer.com/article/10.1007/s11046-020-00523-z 10.1007/s11046-020-00523-z
institution Universiti Putra Malaysia
building UPM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Putra Malaysia
content_source UPM Institutional Repository
url_provider http://psasir.upm.edu.my/
language English
description Candida albicans has been reported globally as the most widespread pathogenic species contributing candidiasis from superficial to systemic infections in immunocompromised individuals. Their metabolic adaptation depends on glyoxylate cycle to survive in nutrient-limited host. The long term usage of fungistatic drugs and the lack of cidal drugs frequently result in strains that could resist commonly used antifungals and display multidrug resistance (MDR). In search of potential therapeutic intervention and novel fungicidals, we have explored a plant alkaloids, namely arborinine and graveoline for its antifungal potential. Alkaloids belongs to Rutaceae family have been reported with numerous antimicrobial activities. In this study, we aimed to isolate and identify the antifungal active alkaloids of R. angustifolia and assess antifungal effect targeting C. albicans isocitrate lyase (ICL) gene which regulates isocitrate lyase, key enzyme in glyoxylate cycle contributing to the virulence potential of C. albicans. Alkaloids were extracted by bioassay guided isolation technique which further identified by TLC profile and compared with the standard through HPLC and NMR analysis. The antifungal activities of the extracted alkaloids were quantified by means of MIC (Minimum Inhibitory Concentration). The gene expression of the targeted gene upon treatment was analysed using RT-qPCR and western blot. Additionally, this study looked at the drug-likeness and potential toxicity effect of the active alkaloid compounds in silico analysis. Spectroscopic analysis showed that the isolated active alkaloids were characterized as acridone, furoquinoline, 4-quinolone known as arborinine and graveoline. Results showed that each compound significantly inhibited the growth of C. albicans at the dose of 250 to 500 µg/mL which confirm its antifungal activity. Each alkaloid was found to successfully downregulate the expression of both ICL1 gene CaIcl1 protein. Finally, ADMET analysis suggests a good prediction of chemical properties, namely absorption, distribution, metabolism, excretion and toxicity (ADMET) that will contribute in drug discovery and development later on.
format Article
author Mohd Kamal, Laina Zarisa
Ahmed Adam, Mowaffaq Adam
Mohd Shahpudin, Siti Nurfatimah
Shuib, Ahmad Naqeeb
Sandai, Rosline
Mohd Hassan, Norazian
Tabana, Yasser M.
Basri, Dayang Fredalina
Thian, Leslie Lung Than
Sandai, Doblin
spellingShingle Mohd Kamal, Laina Zarisa
Ahmed Adam, Mowaffaq Adam
Mohd Shahpudin, Siti Nurfatimah
Shuib, Ahmad Naqeeb
Sandai, Rosline
Mohd Hassan, Norazian
Tabana, Yasser M.
Basri, Dayang Fredalina
Thian, Leslie Lung Than
Sandai, Doblin
Identification of alkaloid compounds arborinine and graveoline from Ruta angustifolia L. Pers for their antifungal potential against isocitrate lyase ICL1 gene of candida albicans
author_facet Mohd Kamal, Laina Zarisa
Ahmed Adam, Mowaffaq Adam
Mohd Shahpudin, Siti Nurfatimah
Shuib, Ahmad Naqeeb
Sandai, Rosline
Mohd Hassan, Norazian
Tabana, Yasser M.
Basri, Dayang Fredalina
Thian, Leslie Lung Than
Sandai, Doblin
author_sort Mohd Kamal, Laina Zarisa
title Identification of alkaloid compounds arborinine and graveoline from Ruta angustifolia L. Pers for their antifungal potential against isocitrate lyase ICL1 gene of candida albicans
title_short Identification of alkaloid compounds arborinine and graveoline from Ruta angustifolia L. Pers for their antifungal potential against isocitrate lyase ICL1 gene of candida albicans
title_full Identification of alkaloid compounds arborinine and graveoline from Ruta angustifolia L. Pers for their antifungal potential against isocitrate lyase ICL1 gene of candida albicans
title_fullStr Identification of alkaloid compounds arborinine and graveoline from Ruta angustifolia L. Pers for their antifungal potential against isocitrate lyase ICL1 gene of candida albicans
title_full_unstemmed Identification of alkaloid compounds arborinine and graveoline from Ruta angustifolia L. Pers for their antifungal potential against isocitrate lyase ICL1 gene of candida albicans
title_sort identification of alkaloid compounds arborinine and graveoline from ruta angustifolia l. pers for their antifungal potential against isocitrate lyase icl1 gene of candida albicans
publisher Springer
publishDate 2021
url http://psasir.upm.edu.my/id/eprint/97595/1/ABSTRACT.pdf
http://psasir.upm.edu.my/id/eprint/97595/
https://link.springer.com/article/10.1007/s11046-020-00523-z
_version_ 1739829915472101376
score 13.211869

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