Structure-Based Computational Screening of N1-(1-(1H-Benzo[d]imidazol-2-yl)ethyl)benzene-1,4-diamine Derivatives as Antibacterial Agents Against Streptococcus pneumoniae
نویسندگان
1 Narayan Institute of Pharmacy, Gopal Narayan Singh University, Jamuhar, Sasaram (Rohtas) Bihar - 821305, India
2 A. M. Reddy Memorial College of Pharmacy, Narsaraopet, Andhra Pardesh, India
3 Rajib Lochan Hota College of Pharmacy, Maheswari Vihar, Mahada, Barpali, 768029, Odisha, India
4 School of Electronic Science and Engineering, University of Electronic Science and Technology of China, Chengdu, 610054, China
5 Department of Pharmaceutical Analysis, Anurag University, Venkatapur, Ghatkesar Rd, Hyderabad Telangana-500088, India
6 Mallareddy Institute of Pharmaceutical Sciences, MRVU Misammaguda, Dhulapally, Kompally, Medchel, Telangana, India
7 Mallareddy Institute of Pharmaceutical Sciences, MRVU Misammaguda, Dhulapally, Kompally, Medchel, Telangana, India
8 Mallareddy Institute of Pharmaceutical Sciences, MRVU Misammaguda, Dhulapally, Kompally, Medchel, Telangana, India
9 Department of Pharmacology, School of Pharmacy and Life Sciences, Centurion University of Technology and Management, Bolangir, 767001, Odisha, India
10 The Pharmaceutical College Samaleswari Vihar, Tingipali, Barpali Odisha, India
doi
10.48309/ajca.2026.572273.2039چکیده
The increasing prevalence of antibiotic-resistant Streptococcus pneumoniae highlights the urgent need for new antibacterial scaffolds with improved efficacy and favorable pharmacokinetic profiles. In this study, a series of N1-(1-(1H-benzo[d]imidazol-2-yl)ethyl)benzene-1,4-diamine derivatives (RS1–RS30) were rationally designed and synthesized by varying the benzimidazole R₁ substituent (H or CH₃) and terminal aryl (—Ar) moieties of the compounds. Molecular docking studies were performed against the S. pneumoniae target protein (PDB ID: 5ZQ0), revealing that most of the synthesized compounds exhibited stronger binding affinities (−7.5 to −9.9 kcal/mol) than the native ligand (−7.9 kcal/mol). Notably, compounds RS24 (−9.9 kcal/mol), RS9 (−9.7 kcal/mol), RS2 (−9.6 kcal/mol), RS1 (−9.5 kcal/mol), RS16 (−9.5 kcal/mol), and RS17 (−9.5 kcal/mol) demonstrated highly stable interaction profiles through salt bridge formation, hydrogen bonding, and hydrophobic interactions with the key residues GLU333, PHE281, LYS385, and TYR312. Comprehensive in silico ADMET analysis indicated that the synthesized derivatives possessed improved physicochemical properties, including optimized molecular weights (340–444 Da), reduced TPSA values (53–113 Ų), and favorable lipophilicity (logP ~3.0–5.2) compared with the native ligand (TPSA 182.63 Ų). Most compounds showed enhanced predicted absorption (high F50% values up to ~0.98), acceptable distribution behavior, manageable CYP interaction profiles, and reduced toxicity risk. Collectively, these findings suggest that the synthesized benzimidazole derivatives are promising lead candidates for further experimental validation as antibacterial agents against S. pneumoniae.
