Urethral complex thickness and thickness index are the independent risk factors for urethroplasty complications after tubularized incised plate hypospadias repair.

INTRODUCTION: In tubularized incised plate urethroplasty, the depth of the mid-line relaxing incision is the key factor for urethral plate tubularization without tension. The incision depths will be different from one case to the other even if they have been done by the same surgeon. This difference in depths resulted from the different thicknesses of the urethral plate and the underlying corpus spongiosum (urethral complex). OBJECTIVES: To evaluate the urethral complex thickness and thickness index as risk factors for the complications of TIPU in penile shaft hypospadias repair. STUDY DESIGN: All primary penile shaft (distal and mid-penile) hypospadias (with or without mild penile chordee) were operated with TIPU between March 2018 and February 2021. We measured the urethral complex thickness in the hypospadiac and proximal normal parts of urethra pre-operatively with superficial U/S probe. Intraoperative, we measured the urethral plate width before and after the midline relaxing incision, calculate the relative increase in urethral plate width (RIUPW). Stepwise logistic regression assessed the effect of different variables on the complication rate. These variables include; urethral plate width before and after incision, urethral complex thickness, thickness index, RIUPW, site of hypospadiac meatus and patients ages. RESULTS: 10 cases had 11 complications (12.7%). Fistulae were the commonest complication (8.9%). Complication rate has significant negative correlations with many variables on Univariate analysis. Stepwise logistic regression shows that urethral plate thickness and thickness index are the independent risk factors for complications after TIPU in penile shaft hypospadias. DISCUSSION: Urethral plate width was suggested to be a risk factor for TIPU complications. In our study, Univariate analysis shows that complications were more with plate width ˂8 mm but without significant difference (P = 0.487). Also it shows that post incision width and RIUPW have significant negative correlation with complications rate. Multivariate analysis showed that the urethral complex thickness and thickness index are the independent risk factors for complications after TIPU hypospadias repair (AUC 0.94 95% CI 0.894-0.972 P Ë‚ 0.001 and 0.965 95% CI 0.921-0.996, respectively). CONCLUSION: The thickness of the urethral plate and the underlying spongiosum is the determining factor for TIPU success. We can use it as an objective reproducible assessment tool for urethral plate quality and to predict TIPU complications.

A Multi-Element-Doped Porous Bioactive Glass Coating for Implant Applications.

OBJECTIVES: The objectives of the study were (1) to develop a novel multi-element-doped porous 58S bioactive glass coating for titanium implants and (2) to investigate the physiochemical, cell cytotoxic and antibacterial properties of this novel coating for titanium implants. METHODS: This study employed the sol-gel method to develop a silver-, cobalt (II) oxide- and titanium dioxide-doped 58S bioactive glass coating. The surface topography and in vitro bioactivity of the new bioactive glass-coated implants were studied using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy. The surface nanohardness and coating degradation were evaluated using atomic force microscopy (AFM) and inductively coupled plasma atomic emission spectroscopy (ICP-AES), respectively. The cell cytotoxicity was assessed using cell viability of osteoblast-like mouse cells. The antibacterial property was examined using colony-forming units (CFUs) of the implant coating against Porphyromonas gingivalis. RESULTS: The multi-element-doped porous 58S bioactive glass-coated titanium implant was synthesized. SEM showed that calcium phosphate was formed on the novel coating but not on the 58S bioactive glass coating. The mean surface nanohardness of the novel coating and the 58S coating were 124 ± 24 and 50 ± 17 MPa, respectively (p < 0.001). ICP-AES showed that the releases of Si, Ca and P ions of the novel coating were significantly higher than that of a 58S bioactive glass-coated implant. No significant difference in cell cytotoxicity was found between the novel coating and the 58S coating (p > 0.1). The mean CFUs of the novel coating and the conventional coating were 120 × 106 and 49 × 106 /mL. CONCLUSION: A novel multielement-doped porous bioactive glass coating for titanium implants was developed. The coating displays promising biocompatibility and antibacterial activity. CLINICAL SIGNIFICANCE: the coating can be used to improve the clinical success of dental implants for patient care if it shows success in clinical trials.

Miniature semi-rigid ureteroscopy with holmium-yttrium-aluminium-garnet laser vs shockwave lithotripsy in the management of upper urinary tract stones >1 cm in children.

OBJECTIVE: To compare the efficacy and safety of miniature semi-rigid ureteroscopy (URS) with holmium (Ho)-yttrium-aluminium-garnet (YAG) laser lithotripsy vs shockwave lithotripsy (SWL) for treating upper urinary tract (UUT) calculi >1 cm in children. PATIENTS AND METHODS: Children with unilateral single UUT ureteric stones of >1 cm were prospectively enrolled in this study. Patients were randomly divided into two groups: Group 1, treated with SWL; and Group 2, treated with URS (6/7.5 F) and laser lithotripsy. The patients' characteristics, stones demographics, operative time, adjunctive procedures, stone-free rate (SFR), re-treatment rate, and complications were statistically analysed and compared. Success was defined as stone-free status (no stone residual of ≥0.3 cm) at 1 month from the initial treatment without any auxiliary procedures. RESULTS: In all, 68 patients with UUT stones met our inclusion criteria. There were no significant differences between the two groups for patient or stone demographics. In Group 1, the SFR was 26/34 (76.4%) and in Group 2 it was 33/34 (97.1%) (P = 0.03). A total of 12 auxiliary procedures in Group 1 and two in Group 2 were needed to reach a 100% SFR (P = 0.014). There were no significant differences between the two groups for operative times, adjunctive procedures, number of complicated cases or complications of Grade ≥III (P = 0.65, P = 0.23, P = 0.77, and P = 0.62, respectively). CONCLUSION: Miniature semi-rigid URS with Ho-YAG laser lithotripsy for UUT ureteric stones of >1 cm in children was more effective than SWL in terms of SFR and re-treatment rate, with no significant difference in the rate or grade of complications. ABBREVIATIONS: EQ: efficiency quotient; KUB: plain abdominal radiograph of the kidneys, ureters and bladder; RCT: randomised controlled trial; SFR: stone-free rate; SWL: shockwave lithotripsy; URS: ureteroscopy; US: ultrasonography/ultrasound; URS: ureteroscopy; UUT: upper urinary tract; YAG: yttrium-aluminium-garnet.

Diagnostic utility of amylase α-1A, MOC 31, and CD 82 in renal oncocytoma versus chromophobe renal cell carcinoma.

OBJECTIVE: Renal oncocytoma (RO) and chromophobe renal cell carcinoma (ChRCC) originate from the same cell origin, that is, the intercalated cells of the collecting duct.[1] In most cases, there are clear morphologic differences between RO and ChRCC; however, in some instances, overlapping features may be encountered and the differentiation between the two entities becomes difficult.[2] Several immunohistochemical markers with different expression patterns in ChRCC and RO have been described to rule out this dilemma. MATERIALS AND METHODS: About 47 primary renal neoplasms that had been diagnosed as RO or ChRCC were submitted for immunohistochemical staining of amylase α-1A (AMY1A), MOC 31, and CD 82. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy have been analyzed. RESULTS: AMY1A positivity was observed in all RO cases in our work with 91.7% sensitivity and 100% specificity in the diagnosis of RO. The PPV of its expression was (100%) and NPV (97.2%) with a diagnostic accuracy of 97.9%. A significant high expression of MOC 31 was observed in ChRCC compared to its expression in RO with a statistical significance (P < 0.001). In addition, we obtained 82.9% sensitivity and 91.7% specificity of MOC 31 expression in the diagnosis of ChRCC. The positive predictive value (PPV) was (96.7%), negative predictive value (NPV) (64.7%) with diagnostic accuracy (85.1%). In our studied cases, we detected positive immunoexpression of CD 82 in 10 cases (83.3%) of ChRCC. However, it was lost in all RO cases (100%). CD 82 sensitivity and specificity in differentiating ChRCC from RO were 100% and 83.3%, respectively. CONCLUSION: We propose MOC 31 and CD 82 as negative immunostains for RO, as these markers are commonly expressed in ChRCC. In conjunction with AMY1A strong immunopositivity in RO cases, we provide a triple panel of biomarkers (AMY1A, MOC 31, and CD 82) for the distinction between RO and ChRCC.

Renal protective effect of N-acetylcysteine with stepwise ramping voltage against extracorporeal shock wave lithotripsy-induced renal injury: a prospective randomized trial.

PURPOSE: To evaluate the role of combination of N-acetylcysteine with stepwise ramping voltage in renal protection against the ischemic, vascular and oxidative effects of extracorporeal shock wave lithotripsy. PATIENTS AND METHODS: A prospective randomized trial on 164 adult patients scheduled for ESWL for single renal stones. Patients with radio-lucent stones, diabetes, hypertension, febrile UTI, and preoperative albuminuria were excluded from the study. Patients were randomized into one of four groups. Group A patients received maximal fixed voltage of ESWL. Group B patients received stepwise ramping voltage of ESWL. Group C patients received fixed maximal voltage with N-acetylcysteine (NAC) 600 mg/bid from 48 h before to 24 h after the procedure. Group D patients received gradual ramping voltage with NAC. Urinary ß2-microglobulin, 24 h albumin and N-acetyl-ß-D-glucosaminidase/creatinine ratio at 1 day and 5 days post-ESWL and the stone free rate at 2 weeks were measured. RESULTS: Group D was the only group that showed no significant difference pre and post ESWL in urinary albumin, ß2-microglobulin and N-acetyl-ß-D-glucosaminidase/creatinine ratio. Post hoc analysis revealed no significant difference between group B and group C in albumin, ß2-microglobulin N-acetyl-ß-D-glucosaminidase/creatinine ratio, but both of them had significantly lower levels than group A and significantly higher levels than group D. There was no statistically significant difference between all groups in the stone free rate at 2 weeks. CONCLUSION: N-acetylcysteine protects the kidney against ESWL-induced renal injuries especially if combined with stepwise ramping voltage.

New Potent 5α- Reductase and Aromatase Inhibitors Derived from 1,2,3-Triazole Derivative.

This work describes the utility of pyrazole-4-carbaldehyde 1 as starting material for the synthesis of a novel potent series of 5α-reductase and aromatase inhibitors derived from 1,2,3-triazole derivative. Condensation of 1 with active methylene and different amino pyrazoles produced the respective Schiff bases 2-4, 8 and 9. On the other hand, 1 was reacted with ethyl cyanoacetate and thiourea in one-pot reaction to afford the pyrazolo-6- thioxopyridin-2-[3H]-one (10). Moreover, α-ß unsaturated chalcone derivative 11 was prepared via the reaction of compound 1 with P-methoxy acetophenone, which in turn reacted with each of ethyl cyanoacetate, malononitrile, hydrazine hydrate, and thiosemicarbazide to afford the corresponding pyridine and pyrazole derivatives 13, 14, 17, and 20. The structure of newly synthesized compounds was characterized by analytical and spectroscopic data (IR, MS and NMR). All new compounds were evaluated against 5α-reductase and aromatase inhibitors and the results showed that many of these compounds inhibit 5α-reductase and aromatase activity; compound 13 was found to be the highest potency among the tested samples comparing with the reference drugs.

Potent Anti-Ovarian Cancer with Inhibitor Activities on both Topoisomerase II and V600EBRAF of Synthesized Substituted Estrone Candidates.

A series of 16-(α-alkoxyalkane)-17-hydrazino-estra-1(10),2,4-trien[17,16-c]-3-ol (3a-l) and estra-1(10),2,4-trien-[17,16-c]pyrazoline-3-ol derivatives (4a-d) were synthesized from corresponding arylidines 2a,b which was prepared from estrone 1 as starting material. Condensation of 1 with aldehydes gave the corresponding arylidine derivatives 2a,b which were treated with hydrazine derivatives in alcohols to give the corresponding derivatives 3a-l, respectively. Additionally, treatment of 2a,b with methyl- or phenylhydrazine in ethanolic potassium hydroxide afforded the corresponding N-substituted pyrazoline derivatives 4a-d, respectively. All these derivatives showed potent anti-ovarian cancer both in vitro and in vivo. The mechanism of anti-ovarian cancer was suggested to process via topoisomerase II and V600EBRAF inhibition.

In Vitro and In Vivo Anti-Breast Cancer Activities of Some Synthesized Pyrazolinyl-estran-17-one Candidates.

A series of estrone derivatives, 2⁻4, were synthesized from the corresponding arylidine estrone, 2a,b, as starting materials, which were prepared by condensation of estrone (3-hydroxy-estran-17-one, 1) with 4-bromobenzaldehyde and thiophene-2-aldehyde. Treating of 2a,b with hydrazine derivatives in acetic acid or propionic acid afforded pyrazoline derivatives, 3a⁻f and 4a⁻f, respectively. Furthermore, results proved the superiority of thienyl derivatives over 4-bromophenol derivatives in terms of cytotoxic effects on MCF-7 cancer cells. In vivo xenograft breast cancer animal model experiments revealed that the synthesized derivatives can be used for decreasing tumor volume, while the most potent derivative (4f) decreased the development of tumor volume by about 87.0% after 12 days.

Discovery of new indomethacin-based analogs with potentially selective cyclooxygenase-2 inhibition and observed diminishing to PGE2 activities.

New ring-extended analogs of indomethacin were designed based on the structure of active binding site of both COX-1 and COX-2 isoenzymes and the interaction pattern required for selective inhibition of COX-2 to improve its selectivity against COX-2. The strategy adopted for designing the new inhibitors involved i) ring extension of indomethacin to reduce the possibility of analogs to be accommodated into the narrow hydrophobic tunnel of COX-1, ii) deletion of carboxylic acid to reduce the possibility of inhibitor to form salt bridge with Arg120 and eventually prevent COX-1 inhibition, and iii) introduction of methylsulfonyl group to increase the opportunity of the analogs to interact with the polar side pocket that's is crucial for inhibition process of COX-2. The three series of tetrahydrocarbazoles involving 4, 5, 9, 10 and 12 were synthesized in quantitative yields adopting limited number of reaction steps, and applying laboratory friendly reaction conditions. In vitro and in vivo assays for data profiling the new candidates revealed the significant improvement in the potency and selectivity against COX-2 of 6-methoxytetrahydrocarbazole 4 (IC50 = 0.97 µmol) to verify the effect of ring extension in comparison to indomethacin (IC50 = 2.63 µmol), and 6-methylsulfonyltetrahydrocarbazole 10a (IC50 = 0.28 µmol) to verify the effect of ring extension and introduction of methylsulfonyl group. 9-(4-chlorobenzoyl)-6-(methylsulfonyl)-1,2,3,9-tetrahydro-4H-carbazol-4-one 12a showed the most potential and selective activity against COX-2 (IC50 = 0.23 µmol) to be with superior potency to Celecoxib (IC50 = 0.30 µmol). Consistently, 12a was the most active with all the other anti-inflammatory test descriptors and its activity in diminishing the PGE2 with the other analogs confirmed the elaboration of new class of selective COX-2 inhibitors beyond the diarylsulfonamides as a previously common class of selective COX-2 inhibitors. Molecular docking study revealed the high binding score of compound 12a (-30.78 kcal/mol), with less clash contribution (7.2) that is close to indomethacin. Also, 12a showed low conformation entropy score (1.40). Molecular dynamic (MD) simulation identified the equilibrium of both potential and kinetic energies.

Evaluation of ED50 and 5α-reductase inhibitor activities of some thiopyrimidine, pyrane, pyrazoline, and thiazolopyrimidine derivatives.

In this work, twenty-one thiopyrimidine (1-21) candidates containing a pyrane, pyrazoline and thiazolopyrimidine ring screened for their ED50 and 5α-reductase inhibitors comparable to that of Anastrozole as positive drug. Some of the tested product showed moderate 5α-reductase inhibitors with lower toxicity. The detailed ED50 and 5α-reductase inhibitor activities of the synthesized compounds were studied.

3-Substituted-4-hydroxycoumarin as a new scaffold with potent CDK inhibition and promising anticancer effect: Synthesis, molecular modeling and QSAR studies.

A new series of 3-substituted-4-hydroxycoumarin derivatives was designed, synthesized, and evaluated for CDK inhibiting and anticancer activities. All the synthesized target compounds showed remarkably high affinity and selectivity towards CDK1B, compared to flavopiridol, with Ki values in the low nanomolar range (Ki=0.35-0.88nM). Most of them elicited considerable inhibiting effect against CDK9T1 (Ki=3.26-23.45nM). Moreover, all the target compounds were tested in vitro against eighteen types of human tumor cell lines. The hydrazone 3a, N-phenylpyrazoline derivative 6b and 2-aminopyridyl-3-carbonitrile derivative 8c were the most potent anticancer agents against MCF-7 breast cancer cell line (IC50=0.21, 0.21 and 0.23nM, respectively). The target compounds 3a, 6b and 8c were further evaluated in MCF-7 breast cancer mouse xenograft model and showed in vivo efficacy at 10mg/kg dose. The docking study confirmed a unique binding mode in the active site of CDK1B with better score than flavopiridol. Quantitative structure activity relationship study was done and revealed a highly predictive power R(2) of 0.81.

New Potent SARS-CoV 3C-Like Protease Inhibitors Derived from Thieno[2,3-d]-pyrimidine Derivatives.

2-Amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (1) condensed with carbaldehydes 2a,b to give the respective thienopyrimidines (3a,b), which reacted with phosphoryl chloride and hydrazine hydrate to afford the respective pyrimidinohydrazines (4a,b). Compound 4a condensed with acetophenone under Vilsmeier conditions to afford the formylated pyrazolopyrimidine 6. Condensation of 4a with active methylenes produced the respective pyrazolopyrimidines (7-11). Besides, 4a condensed with succinic anhydride and with phthalic anhydride, yielding the pyrrolidine-2,5-dione 12 and the isoindoline-1,3-dione 13, respectively. Moreover, 4a reacted with isatin to afford the hydrazono-indolin-2-one 14. Structural elucidations for the new thienopyrimidines were based upon compatible analytical and spectroscopic results. Eleven of the new compounds were tested and found active against influenza A neuraminidase virus (H3N2). Compounds 12 and 13 were the most potent.

Synthesis of androstanopyridine and pyrimidine compounds as novel activators of the tumor suppressor protein p53.

A series of androstane derivatives 2-16 were synthesized from 3ß-hydroxyandrostan-17-one derivatives (1a-e). Compounds (1a,b) were treated with ethyl cyanoacetate, cyanoacetamide, or malononitrile and gave the corresponding derivatives 2-7, respectively. Additionally, compounds (1a-e) were condensed with cyanothioacetamide, urea, or guanidine hydrochloride afforded the corresponding derivatives 8-12, which then by Moffat oxidation gave the oxidized derivatives 9, 11 and 13, respectively. Finally, compound (1) condensed with acetyl acetone or ethyl acetoacetate gave cyclohexene derivatives (14a-c) and (15a,b), respectively. Compound 15 was oxidized with a Moffat oxidizing agent and afforded the corresponding oxidized compound 16. The newly synthesized compounds activated the tumor suppressor p53 in cancer cells through inhibition of the p53-specific ubiquitin E3 ligase HDM2.

Design and Synthesis of Imidazopyrazolopyridines as Novel Selective COX-2 Inhibitors.

The usefulness of non-steroidal anti-inflammatory drugs (NSAIDs) is hampered by their gastrointestinal side effects. Non-selective cyclooxygenases inhibitors interfere with both COX-1 and COX-2 isozymes. Since COX-1 mediates cytoprotection of gastric mucosa, its inhibition leads to the undesirable side effects. On the other hand, COX-2 is undetectable in normal tissues and selectively induced by inflammatory stimuli. Therefore, it is strongly believed that the therapeutic benefits derive from inhibition of COX-2 only. The presence of a strong connection between reported COX-2 inhibitors and cardiac toxicity encourages medicinal chemists to explore new scaffolds. In the present study, we introduced imidazopyrazolopyridines as new potent and selective COX-2 inhibitors that lack the standard pharmacophoric binding features to hERG. Starting from our lead compound 5a, structure-based drug-design was conducted and more potent analogues were obtained with high COX-2 selectivity and almost full edema protection, in carrageenan-induced edema assay, in case of compound 5e. Increased bulkiness around imidazopyrazolopyridines by adding a substituted phenyl ring(s) afforded less active compounds.

Design, synthesis and biological evaluation of novel condensed pyrrolo[1,2-c]pyrimidines featuring morpholine moiety as PI3Kα inhibitors.

Four series of condensed pyrrolo[1,2-c]pyrimidines 6a-d, 8a-d, 10a,b and 12a-e designed as PI3Kα inhibitors were synthesized and evaluated for inhibitory activity and selectivity toward different PI3K isoforms. The tested compounds displayed PI3Kα kinase inhibitory activity at either low micromolar or nanomolar level. In particular, the morpholino-pyrimidopyrrolopyrimidinones 8a-d and morpholino-pyridopyrrolopyrimidine-2-carbonitriles 12a-e proved to be highly potent and selective PI3Kα inhibitors (IC50 = 0.1-7.7 nM). Moreover, the target compounds exhibited considerable cytotoxic activity against cervical cancer cell line HeLa that over-expresses p110α (0.21-1.99 µM). Molecular modeling simulation revealed that, the designed compounds docked well into p110α active site and their complexes are stabilized by a key H-bonding with the backbone amide of Val851 as well as other favorable hydrophobic and H-bond interactions with different amino acids within the enzyme active site.

New benzimidazoles and their antitumor effects with Aurora A kinase and KSP inhibitory activities.

A newly synthesized series of anticancer compounds comprising thiazolo[3,2-a]pyrimidine derivatives 6a-q bearing a benzimidazole moiety was produced via a one-pot reaction of N-(4-(1H-benzo[d]imidazol-2-yl)phenyl)-2-cyanoacetamide 5 with 2-aminothiazole and an appropriate aromatic aldehyde. Compound 7 was obtained via the reaction of 4-(1H-benzo[d]imidazol-2yl)benzenamide 1 with carbon disulphide and methyl iodide in the presence of concentrated aqueous solution of NaOH, then treated with o-phenylenediamine to give N-(4-1H-benzo[d]imidazol-2-yl)phenyl)-1H-benzo[d]imidazol-2-amine 8. The structures of the newly synthesized compounds were confirmed by analytical and spectroscopic measurements (IR, MS, and (1) H NMR). The synthesized products were screened and studied for their in vitro antitumor activity against three human cancer cell lines (namely colorectal cancer cell line HCT116, human liver cancer cell line HepG2, and human ovarian cancer cell line A2780) and their Aurora A kinase and KSP inhibitory activities. All newly synthesized compounds revealed marked results comparable with the standard drug CK0106023. The compounds 6e and 6k of the thiazolopyrimidine derivatives were the most active compounds when tested against the three cell lines in comparison with the standard drug CK0106023, and showed potent dual KSP and Aurora A kinase inhibition.

Synthesis of a new series of angiotensin II receptor antagonists and antibacterial agents.

2-(Arylmethylenehydrazono)-4,4-diphenyl-1H-imidazol-5(4H)-one 3 underwent regioselective cyclization upon treatment with bromine in acetic acid containing sodium acetate to give the respective 3-substituted-6,6-diphenyl-6,7-dihydro-imidazo[2,1-c][1,2,4]triazole-5-one 4 in overall good yields and not the isomeric structure 5. In addition, compound 4 was synthesized by alternative method via reaction of compound 1 with different acids in acetic acid. The synthesized hydrazone derivatives were screened for their angiotensin II receptor antagonists activity and the results showed promising activity. Also, imidazo[2,1-c][1,2,4]triazole-5-ones 4 were screened for the antibacterial activity and the result revealed that two derivatives have excellent activity.

Androgenic-anabolic activities of some new synthesized steroidal pyrane, pyridine and thiopyrimidine derivatives.

In continuation of our previous work, fused steroidal derivatives with pyrane, pyridine, pyrimidine moieties were synthesized and evaluated as androgenic-anabolic agents. Some of the newly synthesized compounds are exhibited pronounced androgenic-anabolic activities.

Site-selective reactions of hydrazonoyl chlorides with cyanoacetic hydrazide and its N-arylidene derivatives and anti-aggressive activity of prepared products.

Reactions of hydrazonoyl halides with cyanoacetic hydrazide and its N-arylidene derivatives proceeded site-selectively and afforded the respective pyrazolo[3,4-d]pyridazine and aldehyde N-(1-aryl-3-acetyl-4-cyanopyrazol-5-yl)hydrazone derivatives. The structures of the products were elucidated on the basis of their spectral and elemental analyses. The anti-aggressive activity of the compounds prepared was screened.

Monoamine oxidase A and B inhibiting effect and molecular modeling of some synthesized coumarin derivatives.

New series of bioactive 7-oxycoumarin derivatives were synthesized and tested for their in vitro and in vivo monoamine oxidase (MAO) A and B inhibitory effect. In vitro studies revealed exceptionally potent and selective MAO-A inhibitors with K(i) values on a picomolar range. The acetohydrazide (3b) and the dioxopyrrolidine derivative (7b) showed the most potent in vitro and in vivo MAO inhibition activity. Moreover, molecular modeling study of the synthesized compounds into MAO-A (PDB: 2Z5X) and MAO-B (PDB: 2XFN) binding sites exhibited direct correlation between AutoDock binding affinity and% inhibition MAO-A (pM) and MAO-B (µM). In addition, the results of in vivo MAO inhibiting properties (ED(50)) of the tested compounds revealed better direct correlation.