De novo design of pimarane diterpenoid compounds as potential alternatives to sarecycline for acne vulgaris treatment

Abstract

Acne vulgaris is a prevalent skin disorder that affects both adolescents and adults and has a major psychological impact. Antibiotic resistance is one issue that current therapies, including antibiotics, must address. A viable approach is to target Cutibacterium acnes , a crucial bacterium in the development of acne. An antibiotic of the tetracycline class called sarecycline shows efficacy despite resistance and adverse effect issues. The purpose of this study is to develop, assess, and compare the efficacy of Sandracopimar (Pimarane diterpenoids) compounds and Sarecycline in the treatment of acne by targeting the 30S ribosomal subunit of Cutibacterium acnes . Sarecycline’s binding affinity and PheSA score were assessed at the 30S ribosomal subunit binding site of Cutibacterium acnes . There were distinct interactions between Sarecycline and the ribosomal subunit, including hydrophobic and hydrogen bonding. Sarecycline demonstrated a strong binding affinity (-8.2 kcal/mol) and a PheSA score of 0.53184 within the Cutibacterium acnes 30S ribosomal subunit binding site. Sandaracopimar-15-ene-6.beta.,8.beta.-diol exhibited a binding affinity of -7.3 kcal/mol and PheSA score of 0.37252. Compound 1, a novel compound derived from Sandaracopimar-15-ene-6.beta.,8.beta.-diol, showed a slightly higher binding affinity (-8.3 kcal/mol) than Sarecycline. The molecular dynamics simulation results reveal that Compound 1 exhibited stability during a specific phase, indicating favorable binding potential with the Cutibacterium acnes 30S ribosomal subunit drug target. The compound demonstrated structural flexibility, advantageous for molecular interactions. The study indicates that Sandracopimar-derived compounds, including Compound 1, show comparable parameters to Sarecycline, suggesting similar activity in targeting the Cutibacterium acnes 30S ribosomal subunit. These compounds may serve as a potential source of novel anti-acne compounds.