caa a22 4500 605512779 CHVBK 20210128100657.0 cr unu---uuuuu 210128e20150801xx s 000 0 eng 10.1007/s00894-015-2741-y doi (NATIONALLICENCE)springer-10.1007/s00894-015-2741-y Monoterpenes as nitrofurantoin resistance modulating agents: minimal structural requirements, molecular dynamics simulations, and the effect of piperitone on the emergence of nitrofurantoin resistance in Enterobacteriaceae [Elektronische Daten] [Ahmad Shahverdi, Sako Mirzaie, Fatemeh Rafii, Marjan Kakavand, Alireza Foroumadi] The effects of different monoterpenes and 2-cyclohexen-1-one on the antibacterial activity of nitrofurantoin against resistant Enterobacter cloacae, were compared and the minimal structural component of monoterpene required for the highest level of resistance-modulating activity was determined. Subinhibitory concentrations of all compounds tested enhanced the antibacterial activity of nitrofurantoin against E. cloacae to different extents. The highest synergistic effect was observed for the monoterpenes, like piperitone, which contained a conjugated ketone and C=C bond in their carbon ring structure. Piperitone also suppressed the emergence of nitrofurantoin-resistant strains of Enterobacteriaceae that were mutagenized by ethyl methanesulfonate. The modes of interaction of carvone, piperitone, and an enzyme inhibitor, benzoate, with nitroreductase were investigated by molecular docking and molecular dynamic (MD) simulation for 20ns. MD simulation supported greater stability of the benzoate and monoterpene-nitroreductase (NR) complexes than of free NR. The results of this investigation are promising for the synthesis of more effective lead compounds to enhance the antibacterial activity of nitro drugs against resistant Enterobacter strains. Springer-Verlag Berlin Heidelberg, 2015 Molecular dynamics nationallicence Monoterpenes nationallicence Nitrofurantoin nationallicence Resistance modulating activity nationallicence Structural activity relationships nationallicence Shahverdi Ahmad Department of Pharmaceutical Biotechnology, Faculty of Pharmacy and Biotechnology Research Center, Tehran University of Medical Sciences, 1417614411, Tehran, Iran aut Mirzaie Sako Department of Biochemistry, Sanandaj Branch, Islamic Azad University, Sanandaj, Iran aut Rafii Fatemeh Division of Microbiology, National Center for Toxicological Research, U. S. FDA, 72079, Jefferson, AR, USA aut Kakavand Marjan Department of Pharmaceutical Biotechnology, Faculty of Pharmacy and Biotechnology Research Center, Tehran University of Medical Sciences, 1417614411, Tehran, Iran aut Foroumadi Alireza Drug Design and Development Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, 1417614411, Tehran, Iran aut Journal of Molecular Modeling Springer Berlin Heidelberg 21/8(2015-08-01), 1-12 1610-2940 21:8<1 2015 21 894 https://doi.org/10.1007/s00894-015-2741-y text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00894-015-2741-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Shahverdi Ahmad Department of Pharmaceutical Biotechnology, Faculty of Pharmacy and Biotechnology Research Center, Tehran University of Medical Sciences, 1417614411, Tehran, Iran aut NATIONALLICENCE 700 1- Mirzaie Sako Department of Biochemistry, Sanandaj Branch, Islamic Azad University, Sanandaj, Iran aut NATIONALLICENCE 700 1- Rafii Fatemeh Division of Microbiology, National Center for Toxicological Research, U. S. FDA, 72079, Jefferson, AR, USA aut NATIONALLICENCE 700 1- Kakavand Marjan Department of Pharmaceutical Biotechnology, Faculty of Pharmacy and Biotechnology Research Center, Tehran University of Medical Sciences, 1417614411, Tehran, Iran aut NATIONALLICENCE 700 1- Foroumadi Alireza Drug Design and Development Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, 1417614411, Tehran, Iran aut NATIONALLICENCE 773 0- Journal of Molecular Modeling Springer Berlin Heidelberg 21/8(2015-08-01), 1-12 1610-2940 21:8<1 2015 21 894