Conformational analysis of two novel cytotoxic C2-substituted pyrrolo[2,3-f]quinolines in aqueous media,organic solvents,membrane bilayers and at the putative active site |
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| Authors: | Nicole Varvarigou Grigorios Megariotis Georgios Leonis Eleni Vrontaki Antigoni-Margarita Maniati Marilena Vlachou Aphrodite Eikosipentaki Rodanthi Kompogennitaki Manthos G Papadopoulos Simona Golic Grdadolnik Dimitri Komiotis Thomas Mavromoustakos Andrew Tsotinis |
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| Institution: | 1. National and Kapodistrian University of Athens, Chemistry Department, Laboratory of Organic Chemistry, Panepistimioupoli-Zografou, 15771 Athens, Greece;2. National Hellenic Research Foundation, Institute of Biology, Medicinal Chemistry and Biotechnology, Vas. Constantinou 48, 11635 Athens, Greece;3. National and Kapodistrian University of Athens, Faculty of Pharmacy, Department of Pharmaceutical Technology, Panepistimioupoli-Zografou, 15771 Athens, Greece;4. National and Kapodistrian University of Athens, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Panepistimioupoli-Zografou, 15771 Athens, Greece;5. Laboratory of Biomolecular Structure, National Institute of Chemistry, Hajdrihova 19, SI-1001 Ljubljana, Slovenia;6. EN-FIST Centre of Excellence, Dunajska 156, SI-1000 Ljubljana, Slovenia;7. Department of Biochemistry and Biotechnology, Laboratory of Organic Chemistry, University of Thessaly, 41221 Larissa, Greece |
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| Abstract: | We have performed: (i) conformational analysis of two novel cytotoxic C2-substituted pyrrolo2,3-f]quinolines 5e and 5g in deuterated dimethylsulfoxide (DMSO-d6) utilizing NOE results from NMR spectroscopy; (ii) molecular dynamics (MD) calculations in water, DMSO and dimyristoyl phosphatidylcholine bilayers and (iii) molecular docking and MD calculations on DNA nucleotide sequences. The obtained results for the two similar in structure molecules showed differences in: (i) their conformational properties in silico and in media that reasonably simulate the biological environment; (ii) the way they are incorporated into the lipid bilayers and therefore their diffusion ability and (iii) molecular docking capacity as it is depicted from their different binding scores. |
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