In silico analysis of isocoumarin compounds targeting lanosterol C-14 α-demethylase and its potential inhibition of ergosterol synthesis in Candida albicans

• Main Authors: Avante, Gabrielle Vaughn Alyssa, Dela Cruz, Cayne Ashley D., Fernandez, Miles C.
• Format: text
• Language: English
• Published: Animo Repository 2023
• Subjects: Candida albicans > Treatment; Biology
• Online Access: https://animorepository.dlsu.edu.ph/etdb_bio/54
• Institution: De La Salle University

Candida spp. is known to cause infections such as candidiasis, with Candida albicans as the most common causative agent of the disease. Although there is an abundance of antifungal compounds and agents that are currently being utilized for its treatment, recent studies have shown that there is an emergence of antifungal drug resistance. With this, the discovery of novel bioactive antifungal agents such as isocoumarins is vital. Isocoumarins have been found to be promising candidates in the search for novel antifungal agents and its biological activities. The study aimed to determine the ligand-receptor interactions of the top ten binding isocoumarin compounds with lanosterol C-14 𝛼-demethylase of Candida albicans via molecular docking and its potential to inhibit the biosynthesis of ergosterol. The 307 isocoumarin compounds from endophytic fungi were screened for their absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters and drug-likeness properties and were assessed for their binding affinities. The ten best binding isocoumarins were ran through BIOVIA Studio Visualizer to observe the ligand-receptor interactions involved in the strengthening and stabilizing of the compounds to the C-14 𝛼-demethylase binding site. Sg17-1-4 (Isocoumarin 269) was found to be a promising candidate in targeting the biosynthesis of ergosterol through the inhibition of lanosterol C-14 𝛼-demethylase with a binding affinity of -10.9 kcal/mol. The presence of a lactone ring through conventional hydrogen bonding with the amino acid side chains, and the presence of the heme group near the isocoumarin core may be a key component that contributes to the strong binding affinity of the compound to lanosterol C-14 𝛼-demethylase. By understanding the underlying mechanism as to how isocoumarin compounds interact with C-14 𝛼-demethylase may pave the way for the development of new drug or therapies against Candida infections.