Nikolaropoulos, SotirisDurdagi, SerdarΜαυρομούστακος, ΘωμάςBenetis, Nikolas-P.Kapou, AgnesThirty-eight antileukemic steroidal esters possessing conformationally flexible nitrogen mustards were studied, and the 3D QSAR/CoMFA and CoMSIA methodologies were applied in order to derive the correlation between their structure and the in vivo antileukemic activity. These compounds show significantly reduced toxicity and possibly increased bioavailability compared to free nitrogen mustards and therefore constitute potent antileukemic drugs. Both the CoMFA and CoMSIA studies gave similar results indicating that the steric effect and the hydrophobic/hydrophilic balance especially in the steroidal part of the molecules probably determined their bioactivity. Of paramount interest is the observation that the orientation of the alkylating part of the SMEs toward the surface of ring B of the steroidal skeleton was related with increased activity. Concerning the steroidal part. the presence of hydrophobic groups in rings B and D was found to be important for enhanced activity. Enhancement of antileukemic potency is further observed if hydrophilic/H-bond acceptor groups are present at the positions 7 and 17 of the steroidal skeleton. Leapfrog simulations provided novel compounds which lead our future synthetic endeavor for obtaining SMEs with optimum bioactivity.Washington2254-226410.1021/ci800240mhttps://hdl.handle.net/10442/124111549-9596engAmerican Chemical Society© AMER CHEMICAL SOC© AMER CHEMICAL SOCJournal of Chemical Information and ModelingComputer Science, Information SystemsComputer Science, Interdisciplinary ApplicationsChemistry, Multidisciplinary3D QSAR/CoMFA and CoMSIA Studies on Antileukemic Steroidal Esters Coupled with Conformationally Flexible Nitrogen MustardsΆρθρο σε επιστημονικό περιοδικό2008-11Δημοσίευση σε περιοδικόPublication in journalΧημείαChemical sciencesFrascati 42Επιστήμη ηλεκτρονικών υπολογιστώνComputer ScienceΕπιστημονικό άρθροScientific articleΕθνικό Ίδρυμα Ερευνών (ΕΙΕ)Greek Aggregator OpenArchives.gr | National Documentation Centre (EKT)