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Background: Phenolic Mannich bases were reported as acetylcholinesterase (AChE) inhibitors for the medication of Alzheimer's disease. Carbonic anhydrases (CAs) are molecular targets for anticonvulsant, diuretic and antiglaucoma drugs in the clinic. Phenolic compounds were also mentioned as CA inhibitors. The importance of Mannich bases in drug design inspired our research group to design novel phenolic Mannic bases as potent enzyme inhibitors. Objective: In this study, novel Mannich bases, 1-(3,5-bis-aminomethyl-4-hydroxyphenyl)-3-(4-substitutedphenyl)-2- propen-1-ones (1-9), were designed to discover new and potent AChE inhibitors for the treatment of Alzheimer's disease and also to report their carbonic anhydrase inhibitory potency against the most studied hCA I /II isoenzymes with the hope to find out promising enzyme inhibitors. Methods: Mannich bases were synthesized by the Mannich reaction. The structures of the compounds were elucidated by 1H NMR, 13C NMR, and HRMS. Enzyme inhibitory potency of the compounds were evaluated spectrophotometrically towards AChE and hCA I and II enzymes. Results: The compounds showed inhibition potency in nanomolar concentrations against AChE with Ki values ranging from 20.44±3.17 nM to 43.25±6.28 nM. They also showed CAs inhibition potency with Ki values in the range of 11.76±1.29-31.09±2.7 nM (hCA I) and 6.08 ± 1.18-23.12±4.26 nM (hCA II). Compounds 1 (hCA I), 5 (hCA II), and 4 (AChE) showed significant inhibitory potency against the enzymes targeted. Conclusion: Enzyme assays showed that Mannich derivatives might be considered as lead enzyme inhibitors to design more selective and potent compounds targeting enzyme-based diseases.

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Background: Use of contrast agents (CAs) during CT simula on for treatment planing system leads to changes in electron density. In this study we aimed to inves gate the effect on calculated dose of various concentra ons of CAs on treatment planing systems in different dose calcula on algorithms. Materials and Methods: Contrast agent (0.769 mg/ml Iopromid) -water mixtures at concentra ons of 0%, 1%, 2%, 5% and 10% in total volume of 500 ml for each were made by using five iden cal balloons. Calcula ons were performed by Cobalt-60 and 10 MV linear accelerator devices in CMS XIO treatment planning system. The prescribed dose of 100cGy was given to the center of balloon that is isocenter of SAD technique at 10cm from the surface. The doses at maximum dose depth (dmax) and at 5 cm were calculated according to the separate algorithms by either making or not making a correc on for CA, and the results were recorded. Results: In all algorithms, as contrast ra o increases, the dose values at dmax and 5 cm-depth increase accordingly. When the doses at dmax and 5 cm-depth were compared for Linac and Co-60 in all algorithms, it has been shown that the d max value of Co-60 was higher and the difference was greater in parallel with increasing contrast ra o in comparing with Linac. Conclusion:When required during the planning, the treatment plan should be calculated via providing an electron density correc on by contouring the volume retaining CAs along the beam line.

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