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

## TL;DR

This study explores how natural compounds from Caesalpinia sappan L. bind to a key acne-related enzyme, suggesting they could be effective herbal treatments.

## Contribution

The study reveals unique binding modes of BRA and HEM to C. acnes lipase, offering new insights into natural anti-acne agents.

## Key findings

- BRA and HEM bind to C. acnes lipase with distinct modes compared to conventional drugs.
- HEM interacts with both the lid and catalytic sites of the lipase.
- C. sappan compounds show potential as alternatives to combat antimicrobial resistance in acne treatment.

## Abstract

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.