Computational Prediction of Cinnamomum zeylanicum Bioactive Compounds as Potential Antifungal by Inhibit Biofilm Formation of Candida albicans
Authors: Meylani Vita , Putra Rinaldi Rizal , Miftahussurur Muhammad , Sukardiman Sukardiman , Hermanto Feri Eko , Grahadi Rahmat , Daryono Budi Setiadi , Wibawa Tri , Retnaningrum Endah 
Published: July 2024

The issue of Candida albicans resistance to antifungal agents in the management of candidiasis has emerged as a significant concern, necessitating the development of novel antifungal alternatives to ensure efficacy in the treatment of candidiasis. A notable manifestation of C. albicans pathogenicity is the development of biofilms, which are facilitated by the presence of certain genes known as agglutinin-like sequence (ALS) genes, specifically ALS1 and ALS3. The utilisation of Cinnamomum zeylanicum extract as a potential alternative antifungal agent has promise in addressing fungal resistance, particularly in the context of C. albicans, for the treatment of candidiasis. Bioactive compounds such as cinnamonaldehyde, cyclopentane, eugenic acid, hexadecenoid acid and Pyrantel Hydrochloride are present in C. zeylanicum. This research investigates the mechanistic plausibility of the bioactive chemicals found in C. zeylanicum as agents for combating candidiasis. The study specifically examines the inhibitory effects of these compounds on the Agglutinin-like sequence-1 (ALS1) and ALS3 proteins. The study employs a combination of molecular docking and molecular dynamics simulations to elucidate the complex interactions between the bioactive constituents of C. zeylanicum and ALS1/ALS3 proteins. The ligand exhibited notable binding affinity towards the molecules Cinnamaldehyde, Pyrantel Hydrochloride and Hexadecenoic Acid derived from C. zeylanicum, as seen by their binding affinity values ranging from –4.873 to –6.03 kcal/mol. This indicates their potential effectiveness in altering the activities of the target proteins. The investigation reveals distinct interaction patterns between each chemical and the proteases.  Significantly, Pyrantel Hydrochloride establishes binding interactions with essential catalytic residues in both ALS1 and ALS3. The stability of the Pyrantel Hydrochloride-ALS1/ALS3 complexes is further supported by molecular dynamics simulations, which suggest that these complexes possess a strong inhibitory capacity. The preservation of protein structures appears to be minimally impacted, indicating a prolonged inhibitory effect. The effectiveness of Pyrantel Hydrochloride is emphasized by the numerous hydrogen bonds that are formed and confirmed using free-binding energy calculations. Collectively, the results highlight the plausibility of C. zeylanicum anti-candidiasis action, principally mediated through the inhibition of ALS1 and ALS3. This activity is predominantly facilitated by Pyrantel Hydrochloride. This comprehensive understanding provides a valuable foundation for the development of innovative antifungal strategies in the battle against C. albicans infections.
HIGHLIGHTS

The preservation of the protein structures appears to be mostly unaffected, indicating a prolonged inhibitory effect
The effectiveness of Pyrantel Hydrochloride is emphasized by the numerous hydrogen bonds that are formed and confirmed using free-binding energy calculations
The collective findings emphasize the plausibility of Zeylanicum’s anti-candidiasis activity, principally achieved by the inhibition of ALS1 and ALS3
The comprehensive understanding provides a valuable foundation for the development of innovative antifungal strategies in the battle against C. albicans infections

GRAPHICAL ABSTRACT