Unlocking the Anti-Acne Potential of Halogenated Xanthone and Benzophenone Derivatives: A Synergistic Approach Using In-Vitro and Computational Evaluation. Pavithren Devakrishnan (a*), Nadiah Mad Nasir (a), Bimo Ario Tejo (a), Hanan Hasan (b)
a) Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.
*pavithrendevan[at]gmail.com
b) Department of Food Science, Faculty of Food Science and Technology, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.
Abstract
Acne which is caused by Propionibacterium acnes and Staphylococcus aureus bacteria is the most common skin problem among adolescents and young adults. Topical antibiotics like Tetracycline are commonly used to treat acne but their effectiveness has declined as bacteria develop antibiotic resistance. Thus, this research emphasizes the anti-acne property of new synthetic derivatives of halogenated xanthone and benzophenone since the isolated xanthone and benzophenone derivatives from plants has reported to have antimicrobial properties against acne causing bacteria. For the synthesis of the derivatives, the modified method reported by Grover, Shah and Shah were utilized. Next, the anti-acne potency of the synthesized against S. aureus (ATCC 6538 and ATCC 10832) was screen using well diffusion assay (WDD) and active compounds were selected to identify their minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values. Next, the computational analysis of the desired derivatives was performed by molecular docking with the proteins of P. acnes (PDB ID: 8CVO) and S. aureus (PDB ID: 1JIJ) in Biovia Discovery Studio and the toxicity and druglikeness properties was predicted using SwissADME. Based on the screening results through WDD, compound 1 showed promising anti-acne activity with the recorded inhibition zone of 15.00 mm and 30.67 mm (for S. aureus ATCC 6538 and ATCC 10832 respectively) while for compound 2, 14.33 mm and 17.33 mm for S. aureus ATCC 6538 and ATCC 10832 respectively. Then, the MIC and MBC were evaluated, compound 1 showed 0.250 mg/mL and 0.500 mg/mL respectively for S. aureus ATCC 6538, 0.016 mg/mL and 0.500 mg/mL respectively for S. aureus ATCC 10832. While compound 2 showed 0.062 mg/mL and 0.125 mg/mL respectively for S. aureus ATCC 6538 and 0.031 mg/mL and 0.063 mg/mL respectively for S. aureus ATCC 10832. Next, compound 1 and 2 reveals good binding affinity values towards P. acnes and S. aureus and better interaction with the protein active site. Additionally, the results from the ADMET analysis showed that compound 1 and 2 is predicted to have great drug potential for acne treatment. Therefore, these findings indicated that compound 1 and 2 could be possible to use as the better anti-acne formulation with a guarantee for healthy skin.
