Insights into antibacterial design: Computational modeling of eugenol derivatives targeting DNA gyrase
Heba S. Elsewedy,
Sultan Alshehri,
Adeola T. Kola-Mustapha,
Shaymaa M. Genedy,
Khuzama M. Siddiq,
Bushra Y. Asiri,
Rehab A. Alshammari,
Heba Mohammed Refat M. Selim,
Oluwakorede J. Adedeji,
George Oche Ambrose
Affiliations
Heba S. Elsewedy
Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, P.O. Box 71666, Riyadh 11597, Saudi Arabia; Corresponding author.
Sultan Alshehri
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia
Adeola T. Kola-Mustapha
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, University of Ilorin, Ilorin, Nigeria; College of Pharmacy, Alfaisal University Riyadh, Saudi Arabia
Shaymaa M. Genedy
Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, P.O. Box 71666, Riyadh 11597, Saudi Arabia
Khuzama M. Siddiq
Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, P.O. Box 71666, Riyadh 11597, Saudi Arabia
Bushra Y. Asiri
Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, P.O. Box 71666, Riyadh 11597, Saudi Arabia
Rehab A. Alshammari
Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, P.O. Box 71666, Riyadh 11597, Saudi Arabia
Heba Mohammed Refat M. Selim
Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, P.O. Box 71666, Riyadh 11597, Saudi Arabia; Microbiology and Immunology Department, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo 35527, Egypt
Oluwakorede J. Adedeji
College of Pharmacy, Alfaisal University Riyadh, Saudi Arabia
George Oche Ambrose
University of Ilorin Teaching Hospital, Ilorin, Nigeria; Corresponding author.
The rise of antibiotic resistance underscores the urgent need for novel antibacterial agents. DNA gyrase, an essential enzyme involved in bacterial DNA replication, is a promising target for antibacterial therapy. Computational approaches offer a cost-effective means to design and screen potential inhibitors, such as eugenol derivatives. This study aims to computationally design eugenol derivatives as potential antibacterial agents targeting DNA gyrase, assess their binding affinities, evaluate physicochemical properties, and toxicity, and select lead compounds for further investigation. Molecular docking simulations were conducted to investigate the binding affinities of eugenol derivatives and controls to DNA gyrase. Physicochemical properties and toxicity assessments of eugenol were evaluated. Lead compounds were selected based on drug likeness, toxicity, and binding affinity. Molecular docking studies revealed varying binding affinities of eugenol derivatives to DNA gyrase, with lead compounds exhibiting superior affinity compared to eugenol. Physicochemical properties indicated moderate lipophilicity and low aqueous solubility for eugenol. Toxicity assessment revealed mutagenicity and tumorigenicity. De novo compound synthesis generated 244 novel compounds, with 44 selected based on drug-likeness, toxicity, and binding affinity as lead candidates. These findings provide valuable insights for the development of novel antibacterial agents targeting DNA gyrase, with implications for combating antibiotic resistance.
