Exploring Antiurease Activity of Antibiotics: Insights From In Vitro, SAR, In Silico, DNA Docking, and MD Simulation Studies

ABSTRACT In our continued efforts in search for antibiotics active against Helicobacter pylori (HP), the present work demonstrates the antiurease potential of aminoglycosides, tetracyclines, rifaximin, and chloramphenicol. The most active antibiotics during in vitro assays included tobramycin (IC 50 12.64 ± 0.93 µM), rifaximin (IC 50 19.47 ± 0.83 µM), oxytetracycline (IC 50 37.76 ± 0.75 µM), chloramphenicol (IC 50 58.62 ± 0.84 µM) and kanamycin (IC 50 63.75 ± 0.72 µM). Molecular docking studies revealed that rifaximin exhibited the maximum binding affinity (−8.4 kcal/mol), followed by oxytetracycline and tobramycin. The amino acid residues Asp165 and Asp223 in rifaximin, His221 and His332 in oxytetracycline, and Asn168, Gly279, Asp223, and Cyc321 in kanamycin formed conventional hydrogen bonds, and the complexes were further stabilized by hydrophobic interactions. DNA docking studies revealed minor groove binding with maximum binding free energy −10.6 kcal/mol against rifaximin and major groove binding against oxytetracycline with free energy −9.0 kcal/mol. MD simulations for 100 ns yielded RMSD values of 0.302, 0.228, and 0.275 nm for the kanamycin, oxytetracycline, and rifaximin‐receptor complexes, respectively. Analyses revealed that the strength and specificity of hydrogen bonds significantly contributed to the overall stability of the complexes. The Rg, SASA, and MMPBSA calculations revealed conformational stability and supported the in vitro findings. These studies suggest exploring new antibiotics as potential antiurease agents.