TY - JOUR AU - Gupta, Pranjali AU - Rai, Nishant AU - Gautam, Pankaj PY - 2015/01/01 Y2 - 2024/03/29 TI - ANTICANCER DRUGS AS POTENTIAL INHIBITORS OF AcrAB-TolC OF MULTIDRUG RESISTANT E.coli: AN IN SILICO MOLECULAR MODELING AND DOCKING STUDY JF - Asian Journal of Pharmaceutical and Clinical Research JA - Asian J Pharm Clin Res VL - 8 IS - 1 SE - Original Article(s) DO - UR - https://journals.innovareacademics.in/index.php/ajpcr/article/view/3767 SP - 351-358 AB - <p><strong> </strong></p><p>Objective: Overexpression of AcrAB-TolC protein complex is often associated with the virulence of multidrug-resistant bacteria. Development of an<br />effective efflux pump inhibitors (EPI) can be a major strategy to enhance the effectivity of current antibiotics and to restrain the menace of antibiotic<br />resistance among bacteria. Molecular docking based assessment of anticancer drugs as EPI with comparable docking scores of known putative EPI.<br />Methods: Molecular docking of target proteins (AcrA, AcrB and TolC) of Escherichia coli was carried out with four putative and seven selected<br />anticancer drugs using iGEMDOCK software separately.<br />Results: All the four putative inhibitors (norepinephrine, reserpine, verapamil and trimethoprim) used in the present study binds to AcrA (−41.9<br />kcal/mol, −56.75 kcal/mol, −76.69 kcal/mol and −45.20 kcal/mol respectively), AcrB (−74.61 kcal/mol, −135.97 kcal/mol, −126.66 kcal/mol and<br />−87.57kcal/mol respectively) and TolC (−78.49 kcal/mol, −90.22 kcal/mol, −89.42 kcal/mol and −62.57 kcal/mol respectively) with high affinity and<br />seven drug ligands (etoposide, paclitaxel, tamoxifen, mitomycin and thalidomide, vinblastine methotrexate) showed comparable docking energies<br />(AcrA [−36.44 kcal/mol, −78.23 kcal/mol, −17.04 kcal/mol, −42.96 kcal/mol, −44.94 kcal/mol, −67.96 kcal/mol and −20.15 kcal/mol respectively],<br />AcrB [−128.11 kcal/mol, −132.86 kcal/mol, −104.85 kcal/mol, −98.91 kcal/mol, −96.47 kcal/mol, −108.79 and −106.36 kcal/mol respectively], TolC<br />[−68.42 kcal/mol, −88.29 kcal/mol, −64.69 kcal/mol, −68.28 kcal/mol, −59.36 kcal/mol, −77.28 kcal/mol and −74.52 respectively]) with putative<br />inhibitors.<br />Conclusion: Paclitaxel and vinblastine showed high affinity for all units of AcrAB-TolC of E. coli.<br />Keywords: AcrAB-TolC, Efflux pump, Efflux pump inhibitor, Multidrug resistance, Molecular modeling and docking, Escherichia coli.</p> ER -