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 and Ahmed Adam, Mowaffaq Adam and Mohd. Shahpudin, Siti Nurfatimah and Shuib, Ahmad Naqeeb and Sandai, Rosline and Mohd Hassan, Norazian and Tabana, Yasser and Basri, Dayang Fredalina and Lung Than, Leslie Thian 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). pp. 221-236. ISSN 0301-486X

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Abstract

Candida albicans has been reported glob- ally as the most widespread pathogenic species con- tributing 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 gly- oxylate 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. Addition- ally, this study looked at the drug-likeness and potential toxicity effect of the active alkaloid compounds in silico analysis. Spectroscopic analysis showed that the iso- lated active alkaloids were characterized as acridone, furoquinoline, 4-quinolone known as arborinine and graveoline. Results showed that each compound sig- nificantly inhibited the growth of C. albicans at the dose of 250 to 500 lg/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.

Item Type:	Article (Journal)
Additional Information:	88578/4171
Uncontrolled Keywords:	Ruta angustifolia, anthranilic acid alkaloids, antifungal, Candida albicans
Subjects:	Q Science > QR Microbiology R Medicine > RS Pharmacy and materia medica > RS403 Materia Medica-Pharmaceutical Chemistry
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button):	Kulliyyah of Pharmacy > Department of Pharmaceutical Chemistry Kulliyyah of Pharmacy
Depositing User:	Dr. Norazian Mohd Hassan
Date Deposited:	21 May 2021 13:25
Last Modified:	17 Jun 2021 14:50
URI:	http://irep.iium.edu.my/id/eprint/88578

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