Journal Article

The binding modes of brazilin and hematein from Caesalpinia sappan L. to Cutibacterium acnes lipase: Simulation studies

Chairatana, Phoom, Toviwek, Borvornwat, Sangthong, Winyoo, Pengsawang, Maneenuch, Boonmee, Apaporn, Pongprayoon, Prapasiri

2025

Overview

The growing concern over antimicrobial resistance in Cutibacterium acnes ( C. acnes ) has spurred interest in alternative acne treatments, particularly herbal medicines. This study evaluates the binding affinities of established anti-acne agents—ketoconazole (KET) and tetracycline (TET)—alongside natural compounds, brazilin (BRA) and hematein (HEM), derived from Caesalpinia sappan L. ( C. sappan ), to C. acnes lipase. Through molecular docking and dynamics simulations, we demonstrate that the asymmetric lipase dimer operates independently. Bulky compounds such as KET and TET inhibit lipase activity via π-π interactions, primarily targeting the lid domain. In contrast, smaller ligands BRA and HEM exhibit unique binding modes: BRA mirrors TET by localizing near the lid domain, while HEM shows dual interactions with both the lid and catalytic sites. These results underscore the potential of BRA and HEM as promising anti-acne agents, indicating that C. sappan could be an effective herbal remedy for acne. This study provides a foundation for further exploration of natural products in combating acne and mitigating antimicrobial resistance.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Acne / Active sites / Anti-Bacterial Agents - chemistry / Anti-Bacterial Agents - pharmacology / Antibiotics / Antifungal agents / Antimicrobial resistance / Benzopyrans - chemistry / Benzopyrans - metabolism / Benzopyrans - pharmacology / Binding / Binding sites / Bioflavonoids / Biology and Life Sciences / Caesalpinia - chemistry / Caesalpinia sappan / Care and treatment / Catalytic Domain / Causes of / Chemical properties / Chemical research / Cutibacterium acnes / Fatty acids / Flavones / Flavonoids / Flexibility / Health aspects / Herbal medicine / Humans / Ketoconazole / Ligands / Lipase / Lipase - antagonists & inhibitors / Lipase - chemistry / Lipase - metabolism / Medicine and Health Sciences / Microbial enzymes / Molecular docking / Molecular Docking Simulation / Molecular Dynamics Simulation / Natural products / Pathogenesis / Pharmacokinetics / Physical Sciences / Physiological aspects / Physiology / Propionibacteriaceae - enzymology / Protein Binding / Proteins / Research and Analysis Methods / Simulation / Software / Triglycerides