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A series of coumarin derivatives (1-22), bearing at the 7-position ether, ketone, ester, carbamate, or amide functions of varying size and lipophilicity, were synthesized and investigated for their in vitro monoamine oxidase-A and -B (MAO-A and -B) inhibitory activities. Most of the compounds acted preferentially as MAO-B inhibitors, with IC(50) values in the micromolar to low-nanomolar range. A structure-activity-relationship (SAR) study highlighted lipophilicity as an important property modulating the MAO-B inhibition potency of 7-substituted coumarins, as shown by a linear correlation (n=20, r(2)=0.72) between pIC(50) and calculated log P values. The stability of ester-containing coumarin derivatives in rat plasma provided information on factors that either favor (lipophilicity) or decrease (steric hindrance) esterase-catalyzed hydrolysis. Two compounds (14 and 22) were selected to investigate how lipophilicity and enzymatic stability may affect in vivo MAO activities, as assayed ex vivo in rat. The most-potent and -selective MAO-B inhibitor 22 (=7-[(3,4-difluorobenzyl)oxy]-3,4-dimethyl-1-benzopyran-2(2H)-one) within the examined series significantly inhibited (>60%) ex vivo rat-liver and striatal MAO-B activities 1 h after intraperitoneal administration of high doses (100 and 300 mumol kg(-1)), revealing its ability to cross the blood-brain barrier. At the same doses, liver and striatum MAO-A was less inhibited in vivo, somehow reflecting MAO-B selectivity, as assessed in vitro. In contrast, the metabolically less stable derivative 14, bearing an isopropyl ester in the lateral chain, had a weak effect on hepatic MAO-B activity in vivo, and none on striatal MAO-B, but, surprisingly, displayed inhibitory effects on MAO-A in both peripheral and brain tissues.

The concept of Flettner rotor, a rotating cylinder immersed in a fluid current, with a top-mounted disk, has been analyzed by means of unsteady Reynolds averaged Navier-Stokes simulations, with the aim of creating a suitable tool for the preliminary design of the Flettner rotor as a ship’s auxiliary propulsion system. The simulation has been executed to evaluate the performance sensitivity of the Flettner rotor with respect to systematic variations of several parameters, that is, the spin ratio, the rotor aspect ratio, the effect of the end plates, and their dimensions. The Flettner rotor device has been characterized in terms of lift and drag coefficients, and these data were compared with experimental trends available in literature. A verification study has been conducted in order to evaluate the accuracy of the simulation results and the main sources of numerical uncertainty. All the simulation results were used to achieve a surrogate model of lift and drag coefficients. This model is an effective mathematical tool for the preliminary design of Flettner rotor. Finally, an example of assessment of the Flettner rotor performance as an auxiliary propulsion device on a real tanker ship is reported.

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