Anchor versus parachute suturing technique in arteriovenous fistula creation for hemodialysis.

INTRODUCTION: Chronic kidney disease (CKD) affects 13% of the global population and requires renal replacement therapy due to ESRD. Hemodialysis (HD) is the most common dialysis modality for ESRD patients, but establishing vascular access is challenging due to high morbidity and mortality rates. Arteriovenous fistulas (AVFs) are the gold standard for vascular access, but many fail due to anastomotic hemodynamics, vein diameter, and anastomatic suture technique. A prospective study was conducted to evaluate the impact of two continuous suturing techniques, the anchor technique and the parachute technique, on AVFs' initial outcomes. METHODS: This randomized, controlled study involved adult patients who presented for AVF creation at our center. We divided the patients into two groups: anchors and parachutes. Four skilled vascular access surgeons performed the procedures. The primary goal was functional maturation of the AVF, defined as an AVF fistula ready to be cannulated with a cannulating vein length of at least 10 cm, a diameter of more than 6 mm, a depth of less than 6 mm, and a flow rate of 600 mL/min. Secondary goals included patency and complications such as bleeding, infection, steal syndrome, and aneurysmal dilatation at the anastomosis site. AVFs were evaluated immediately after surgery and during follow-up visits at the outpatient clinic. A duplex scan was performed to measure flow at various intervals. All patients provided appropriate written consent. RESULT: The study involved 186 patients, with 86 excluded. 100 were randomized, with 5 cases losing follow-up and 3 deaths within 12 months. The follow-up continued until January 2024, with a mean of 8.6 months. The Parachute technique shows higher technical success (p value = 0.046) and primary patency at 30 days (p value = 0.014) compared to Anchor, but there is no statistical significance between both groups regarding functional maturation at 6 weeks (p value = 0.352). The parachute technique has a higher hematoma rate than the anchor technique (p value = 0.025), while other complications like intra-operative bleeding, postoperative bleeding, pseudoaneurysm formation, thrombosis, steal syndrome, and seroma formation show no significant differences. Nine patients, five of whom were diabetic and underwent conservative management, exhibited mild to moderate steal syndrome. This suggests an increased risk of steal syndrome among diabetic patients. CONCLUSION: The parachute technique for AVF creation offers better technical success and short-term primary patency outcomes, while both parachute and anchor techniques are equally effective for long-term functional maturation and overall complication rates.

Evaluation of the effect of extraction in comparison to distalization on the maxillary third molars in class II malocclusion: a retrospective study.

OBJECTIVE: To compare the effects of first premolar extraction versus distalization on the vertical position and mesiodistal angulation of maxillary third molars (MxM3) in adolescent class II patients. METHODS: The panoramic x-rays (OPGs) of 200 adolescent class II patients with developing MxM3s were screened. The chosen sample consisted of 2 groups: Group 1 (Distalization) comprising 48 MxM3s, and Group 2 (Extraction) comprising 50 MxM3s. The pre- and post-treatment OPGs were traced to detect the mesiodistal angulation changes of the second molars (MxM2) and MxM3s. RESULTS: The angulation and vertical position of the MxM3s at T0 & T1 were also evaluated using Archer's classification. The distalization group presented a non-significant decrease in the mean angulation of MxM2 and MxM3 (-2.4o & -4.5o uprighting respectively). In the extraction group, both MxM2 and MxM3 presented a highly significant decrease in the mean angulation (-10.5o & -11o uprighting respectively). The angulation and vertical position change of MxM3 significantly improved in the extraction group when compared to the distalization group (P < .001). CONCLUSION: Significant uprighting and occlusal positioning of the maxillary third molars occurred in the premolar extraction treatment group when compared to the distalization treatment group. The results of the current study highlight the importance of recognizing maxillary third molars during orthodontic treatment planning of Class II malocclusion cases.

Credibility of Pont's index in Egyptian population.

BACKGROUND: Many indices have been suggested to help orthodontists in predicting the ideal dental arch width. One of these was Pont's index which was established by Pont. He suggested equations to predict the ideal maxillary dental arch width (interpremolar and intermolar) from the combined mesiodistal width of the maxillary incisors. This study aimed to test the applicability of Pont's index as an orthodontic diagnostic tool in Egyptian population and to compare the results with those obtained from studies of different ethnic subjects. METHODS: This study was performed using dental casts of 184 Egyptian individuals (82 males and 102 females; age range, 19-24 years). The casts were divided into 46 casts with normal occlusion, 46 casts with class I, 46 casts with class II and 46 casts with class III malocclusion, according to Angle's classification. Alginate impressions were taken for all patients and poured immediately using dental plaster. The real models were transformed into digital models using three-dimensional laser scanner to allow digital model analysis. Predicted arch widths were calculated using Pont's equations. The predicted values were compared to the measured values. RESULTS: Intra class correlation coefficient (ICC) (absolute agreement) between measured and predicted arch widths was determined. Poor absolute agreement was found between measured arch width values and the corresponding values calculated according to Pont's index. CONCLUSION: According to the results of this study, Pont's index is not a reliable method for predicting the ideal dental arch widths in Egyptian populations.

Effect of glazing and thermocycling on the fracture toughness and hardness of a New fully crystallized aluminosilicate CAD/CAM ceramic material.

BACKGROUND: The mechanical properties of fully crystallized lithium aluminosilicate ceramics may be influenced by intraoral temperature variations and postmilling surface treatment. The purpose of this study is to explore the interplay among glazing, thermocycling, and the mechanical characteristics (namely, fracture toughness and hardness) of fully crystallized lithium aluminosilicate ceramics. METHODS: Bending bars (n = 40) cut from LisiCAD blocks (GC, Japan) were randomly assigned to glazed or unglazed groups (n = 20) and subjected to the single edge v-notch beam method to create notches. A glazing firing cycle was applied to the glazed group, while the unglazed group was not subjected to glazing. Half of the specimens (n = 10) from both groups underwent thermocycling before fracture toughness testing. The fracture toughness (KIC) was evaluated at 23 ± 1 °C using a universal testing machine configured for three-point bending, and the crack length was measured via light microscopy. Seven specimens per group were selected for the hardness test. Hardness was assessed using a Vickers microhardness tester with a 1 kg load for 20 s, and each specimen underwent five indentations following ISO 14705:2016. The Shapiro-Wilk and Kolmogorov-Smirnov tests were used to evaluate the normality of the data and a two-way ANOVA was utilized for statistical analysis. The significance level was set at (α = 0.05). RESULTS: Regardless of the thermocycling conditions, the glazed specimens exhibited significantly greater fracture toughness than did their unglazed counterparts (P < 0.001). Thermocycling had no significant impact on the fracture toughness of either the glazed or unglazed specimens. Furthermore, statistical analysis revealed no significant effects on hardness with thermocycling in either group, and glazing alone did not substantially affect hardness. CONCLUSIONS: The impact of glazing on the fracture toughness of LiSiCAD restorations is noteworthy, but it has no significant influence on their hardness. Furthermore, within the parameters of this study, thermocycling was found to exert negligible effects on both fracture toughness and hardness.

Effect of artificial aging on fracture toughness and hardness of 3D-printed and milled 3Y-TZP zirconia.

PURPOSE: This study aimed to evaluate the impact of artificial aging on the fracture toughness and hardness of three-dimensional (3D)-printed and computer-aided design and computer-aided manufacturing (CAD-CAM) milled 3 mol% yttria-stabilized tetragonal zirconia polycrystals (3Y-TZP). MATERIALS AND METHODS: Forty bar-shaped specimens (45 × 4 × 3 mm) were prepared using two manufacturing technologies: 3D printing (LithaCon 3Y 210, Lithoz GmbH, Vienna, Austria; n = 20) and milling (Initial Zirconia ST, GC, Japan; n = 20) of 3Y-TZP. The chevron-notch beam method was used to assess the fracture toughness according to ISO 24370. Specimens from each 3Y-TZP group were divided into two subgroups (n = 10) based on the artificial aging process (autoclaving): nonaged and aged. Nonaged specimens were stored at room temperature, while aged specimens underwent autoclave aging at 134°C under 2 bar-pressure for 5 h. Subsequently, the specimens were immersed in absolute 99% ethanol using an ultrasonic cleaner for 5 min. Each specimen was preloaded by subjecting it to a 4-point loading test, with a force of up to 200 N applied for three cycles. Further 4-point loading was conducted at a rate of 0.5 mm/min under controlled temperature and humidity conditions until fracture occurred. The maximum force (Fmax) was recorded and the chevron notch was examined at 30 × magnification under an optical microscope for measurements before the fracture toughness (KIc) was calculated. Microhardness testing was also performed to measure the Vickers hardness number (VHN). A scanning electron microscope (SEM) coupled with an energy dispersive X-ray unit (EDX) was used to examine surface topography and chemical composition. X-ray diffraction (XRD) was conducted to identify crystalline structure. Data were statistically analyzed using two-way ANOVA and Student's t-test with a significance level of 0.05. RESULTS: The nonaged 3D-printed 3Y-TZP group exhibited a significantly higher fracture toughness value (6.07 MPa m1/2) than the milled 3Y-TZP groups (p < 0.001). After autoclave aging, the 3D-printed 3Y-TZP group maintained significantly higher fracture toughness (p < 0.001) compared to the milled 3Y-TZP group. However, no significant differences in hardness values (p = 0.096) were observed between the aged and nonaged groups within each manufacturing process (3D-printed and milled) independently. CONCLUSION: The findings revealed that the new 3D-printed 3Y-TZP produced by the lithography-based ceramic manufacturing (LCM) technology exhibited superior fracture toughness after autoclave aging compared to the milled 3Y-TZP. While no significant differences in hardness were observed between the aged groups, the 3D-printed material demonstrated greater resistance to fracture, indicating enhanced mechanical stability.

Discovery of benzochromene derivatives first example with dual cytotoxic activity against the resistant cancer cell MCF-7/ADR and inhibitory effect of the P-glycoprotein expression levels.

A series of 1H-benzo[f]chromene moieties (4a-z) were synthesised under Ultrasonic irradiation and confirmed with spectral analyses. Derivative 4i solely possessed an X-ray single crystal. The anti-proliferative efficacy of the desired molecules has been explored against three cancer cells: MCF-7, HCT-116, and HepG-2 with the cytotoxically active derivatives screened against MCF-7/ADR and normal cells HFL-1 and WI-38. Furthermore, compounds 4b-d, 4k, 4n, 4q, and 4w, which possessed good potency against MCF-7/ADR, were tested as permeability glycoprotein (P-glycoprotein [P-gp]) expression inhibitors. The attained data confirmed that 4b-d, 4q, and 4w exhibited strong expression inhibition against the P-gp alongside its cytotoxic effect on MCF-7/ADR. The western blot results and Rho123 accumulation assays showed that compounds 4b-d, 4q, and 4w effectively inhibited the P-gp expression and efflux function. Meanwhile, 4b-d, 4q, and 4w induced apoptosis and accumulation of the treated MCF-7/ADR cells in the G1 phase and 4k and 4n in the S phase of the cell cycle.

An investigation on fatigue, fracture resistance, and color properties of aesthetic CAD/CAM monolithic ceramics.

OBJECTIVES: To evaluate and compare fracture resistance, translucency, and color reproducibility, as well as the effect of aging on the fracture load and color stability of novel monolithic CAD/CAM ceramics. MATERIALS AND METHODS: One hundred crowns of uniform thickness were milled from five ceramic blocks (n = 20): partially crystallized lithium disilicate (PLD) and fully crystallized lithium disilicate (FLD), lithium metasilicate (LMS), 4Y-TZP (SMZ), and 5Y-TZP (UMZ) monolithic zirconia. PLD crowns were glazed, LMS was fired, and FLD was polished. SMZ and UMZ crowns were sintered and polished. Crowns were adhesively cemented to epoxy dies. Half of the crowns (n = 10) were subjected to 1.200.000 load cycles with thermal cycling. Color space values L, a, b defined by the Commission Internationale de l´Eclairage (CIELAB) were measured before and after aging, and (∆E) was calculated. Both aged and non-aged specimens were loaded until fracture in a universal testing machine and the fracture load was recorded. X-ray diffraction (XRD) and scanning electron microscope (SEM) fractographic analysis were carried out on fractured fragments of representative samples. For translucency and color reproducibility, 50 rectangular-shaped specimens were fabricated and processed as described previously. Color values were measured over black and white backgrounds, and the translucency parameter (TP) was computed. Using the shade verification mode, (∆E) to shade A3 was calculated. Data were statistically analyzed using one-way and two-way ANOVA, and t-test. RESULTS: Aging did not affect fracture resistance significantly (p > 0.05). The highest mean fracture load was obtained for the SMZ and UMZ. A significant color change was observed after aging in all groups. The highest TP was noted for FLD. SMZ and UMZ had the best shade match. CONCLUSIONS: Zirconia showed higher fracture resistance and color stability than lithium silicate ceramics. Lithium silicate ceramics were more translucent. The experimental FLD demonstrated high translucency. CLINICAL RELEVANCE: Tested ceramics showed sufficient stability to withstand masticatory forces. Characterization of final restorations might be mandatory for better color match.

The effect of cyclic loading on the fracture resistance of 3D-printed and CAD/CAM milled zirconia crowns-an in vitro study.

OBJECTIVES: The aim of this study was to evaluate the effect of cyclic mechanical loading on the fracture resistance of 3D-printed zirconia crowns in comparison to milled zirconia crowns. MATERIALS AND METHODS: Monolithic zirconia crowns (n = 30) were manufactured using subtractive milling (group M) and 3D additive printing (group P). Nine samples of each group were fractured under one-time loading while the other 6 samples were subjected to cyclic loading for 1.2 million cycles before being subjected to one-time loading until fracture. Scanning electron microscope (SEM) fractographic analysis was carried out on fractured fragments of representative samples. RESULTS: The mean for fracture resistance of group M was 1890 N without cyclic loading and 1642 N after being subjected to cyclic loading, and they were significantly higher than that of group P (1658 N and 1224 N respectively). CONCLUSIONS: The fabrication technique and cyclic loading affect the fracture resistance of zirconia crowns. Although the fracture resistance values for the 3D-printed crowns were lower than those of the milled, still they are higher than the masticatory forces and thus could be considered being clinically acceptable. CLINICAL RELEVANCE: Concerning fracture resistance, 3D-printed crowns can withstand the masticatory forces for the long term without any cracks or failure.

Biomimetic approaches and materials in restorative and regenerative dentistry: review article.

Biomimetics is a branch of science that explores the technical beauty of nature. The concept of biomimetics has been brilliantly applied in famous applications such as the design of the Eiffel Tower that has been inspired from the trabecular structure of bone. In dentistry, the purpose of using biomimetic concepts and protocols is to conserve tooth structure and vitality, increase the longevity of restorative dental treatments, and eliminate future retreatment cycles. Biomimetic dental materials are inherently biocompatible with excellent physico-chemical properties. They have been successfully applied in different dental fields with the advantages of enhanced strength, sealing, regenerative and antibacterial abilities. Moreover, many biomimetic materials were proven to overcome significant limitations of earlier available generation counterpart. Therefore, this review aims to spot the light on some recent developments in the emerging field of biomimetics especially in restorative and regenerative dentistry. Different approaches of restoration, remineralisation and regeneration of teeth are also discussed in this review. In addition, various biomimetic dental restorative materials and tissue engineering materials are discussed.

Comparative evaluation of internal fit and marginal gap of endocrowns using lithium disilicate and polyether ether ketone materials - an in vitro study.

BACKGROUND: The aim of the study was to investigate the effect of material and occlusal preparation design on the internal fit and marginal gap of endocrowns made of Polyether ether ketone (PEEK) and lithium disilicate. METHODS: 32 endocrowns were fabricated on prepared mandibular molars and divided into two groups (n = 16) according to the material. Group L: lithium disilicate and Group P: PEEK. Each group was further subdivided into two subgroups (n = 8) according to the occlusal preparation design: full occlusal coverage (LF and PF) and partial occlusal coverage (LP and PP). Samples were analyzed using microcomputed tomography (µCT) with a voxel size of 6 µm to evaluate internal fit, and an optical microscope was used to evaluate the marginal gap. Data were collected, tabulated, and statistically analyzed. Numerical data were described as mean and standard deviation and compared using the ANOVA test. The level of significance was set at α P ≤ 0.05. RESULTS: All groups' internal fit and marginal gaps values were within the acceptable clinical range. However, the lithium disilicates group recorded statistically significantly higher mean internal gap values than the PEEK groups. Regardless of the material, the difference between the two occlusal designs was not statistically significant in both internal fit and marginal gap records. CONCLUSION: Within the limitations of this study, PEEK endocrown restorations revealed better internal fit and marginal gap than lithium disilicate endocrown restorations. The marginal and internal fit of both lithium disilicate and PEEK endocrown restorations were within the clinically acceptable range. The occlusal preparation design had no influence on the internal fit and marginal gap of the endocrown restoration.

Marginal gap and internal fit of 3D printed versus milled monolithic zirconia crowns.

BACKGROUND: This study aimed to evaluate and compare the marginal gap using two different methods and the internal fit of 3D printed and zirconia crowns. METHODS: 3Y-TZP zirconia crowns (n = 20) were manufactured using subtractive milling (group M) and 3D printed (group P). The marginal gap was measured at 60 points using vertical marginal gap technique (VMGT). On the other hand, the silicone replica technique (SRT) was used to evaluate the internal fit and was divided into 4 groups: marginal gap, cervical gap, axial gap, and occlusal gap where the thickness of light impression was measured at 16 references. The numerical data was tested for normality using Shapiro-Wilk's test. They were found to be normally distributed and were analyzed using an independent t-test. RESULTS: Using VMGT, group P had significantly higher mean marginal gap values of 80 ± 30 µm compared to group M = 60 ± 20 µm (p < 0.001). Also, with the SRT, the marginal gap of group P (100 ± 10 µm) had significantly higher values compared to group M (60 ± 10 µm). The internal fit showed significant difference between the tested groups except for Axial Gap. CONCLUSIONS: Although milled crowns showed better results. The 3D printed zirconia crowns offer clinically acceptable results in terms of marginal adaptation and internal fit. Both VMGT and SRT are reliable methods for the assessment of the marginal gap.

Wear behavior and abrasiveness of monolithic CAD/CAM ceramics after simulated mastication.

OBJECTIVES: To evaluate the wear resistance and abrasiveness of monolithic CAD/CAM ceramics. MATERIALS AND METHODS: Rectangular-shaped specimens (12 mm × 6.5 mm × 1.5 mm) were sectioned from the following CAD/CAM blocks (n = 10); partially crystallized lithium disilicate (PLD), experimental fully crystallized lithium disilicate (FLD), zirconia-reinforced lithium silicate (ZLS), super-translucent monolithic zirconia (SMZ), and ultra-translucent monolithic zirconia (UMZ). Silicon carbide papers were used to mechanically flatten and polish the surfaces. PLD specimens were subjected to a combined crystallization/glazing firing cycle. Ceramic specimens were mounted to the wear device and tested for 200,000 cycles against human premolars at 20 N force and 2 mm sliding distance. Artificial saliva was used as a lubricant. The teeth were scanned using micro-CT before and after the wear test and the generated models were overlapped to determine the volumetric tooth loss. Before and after the test, specimens' weights and surface roughness (Ra) values were measured, and the differences were calculated. Scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX) were utilized for microstructural and chemical analysis. Statistical analysis was performed using one-way ANOVA or an equivalent test for non-parametric results. Significance level was set at P ≤ 0.05. RESULTS: The type of ceramic material affected the ceramic and antagonist wear rates (P < 0.001). PLD and ZLS had the highest ceramic and antagonist wear, whereas UMZ and SMZ demonstrated the lowest wear values. The FLD group showed comparable antagonist wear and significantly less ceramic wear than PLD and ZLS. CONCLUSIONS: Monolithic zirconia demonstrated the best wear resistance and least abrasiveness to the antagonist. The experimental lithium disilicate was more wear-resistant than other glass-ceramic groups. CLINICAL RELEVANCE: Monolithic zirconia is wear-resistant and gentle on the antagonist. In contrast, glass-ceramics are more abrasive to enamel.

Facile green synthesis, analysis, in vitro antidiabetic and antimicrobial activity of ZnO macropores.

Rapid increase in population and development in industry causes many problems such as microbial contaminations and chronic diseases such as diabetes. Materials synthesized at nanoscale are novel antidiabetic and antimicrobial agents. ZnO nanoparticles with macropores characteristics are synthesized by green methods. Turmeric, clove buds and green tea extracts are used as additives. X-ray diffraction results confirmed the hexagonal wurtzite structure of ZnO nanoparticles and crystallinity was quit high in case of green tea extract. Sample synthesized with clove shows relatively higher crystallite size (10.64) which is pertaining to variation in Zn2+ and OH- ions. The nanoparticles are more or less spherical in nature, macropores and clustered together revealed by SEM images. Macroporosity of the sample was further confirmed by nitrogen adsorption-desorption isotherm. The deep absorption band at 605 cm-1 in FTIR spectra attributed the wurtzite-type ZnO. The major dominating sharp peak was detected at 437 cm-1 in Raman spectra which is a feature of the wurtzite hexagonal phase ZnO. UV-Vis spectra showed red shift from wavelength 362 to 375 nm with different plant extracts. Impedance analysis showed a high dielectric constant and low tangent loss in case of green tea extract. ZnO synthesized using green tea exhibited ~ 95% α-glucosidase inhibition activity and 91% α-amylase inhibition activity. Antibacterial results revealed that synthesized ZnO nanoparticles showed activity against Bacillus subtilis and E. coli with inhibition zone 35 mm and 29 mm, respectively.

Synthesis of 9-Hydroxy-1H-Benzo[f]chromene Derivatives with Effective Cytotoxic Activity on MCF7/ADR, P-Glycoprotein Inhibitors, Cell Cycle Arrest and Apoptosis Effects.

ß-Enaminonitriles bearing 9-hydroxy-1H-benzo[f]chromene moiety was synthesized. The targeted compounds were evaluated for their anti-proliferative activity against three human tumor cell lines, PC-3, SKOV-3 and HeLa, and the active cytotoxic compounds were further evaluated against cancer cells, MCF-7/ADR, and two normal cell lines, HFL-1 and WI-38. Few compounds were assigned to be the most potent derivatives against PC-3, SKOV-3 and HeLa cell lines in comparison with Vinblastine and Doxorubicin. Several compounds possessed a relatively good potency against MCF-7/ADR cells as compared with Doxorubicin and were tested as a P-gp inhibitor. Moreover, the halogenated substituents, 2,4-F2, 2,3-Cl2, 2,5-Cl2 and 3,4-Cl2; have good potency against P-gp-mediated MDR in MCF-7/ADR as compared with Doxorubicin. Meanwhile, Rho123 accumulation assays revealed that few compounds effectively inhibited P-pg and efflux function. In addition, certain derivatives induced apoptosis and an accumulation of the treated MCF-7/ADR cells in the G1, S and G1/S phases.

Synthesis and evaluation of antitumor activity of 9-methoxy-1H-benzo[f]chromene derivatives.

Herein, a series of aryl-substituted derivatives of 3-amino-1-aryl-9-methoxy-1H-benzo[f]chromene-2-carbonitriles (4a-4q) were designed and synthesized via reaction of 7-methoxy-2-naphthol with a mixture of appropriate aromatic aldehydes and malononitrile under microwave conditions. Among the tested benzochromene, the known compound 4e and four novel compounds 4f, 4j, 4k, 4m exhibited the highest cytotoxicity towards a panel of six human cancer cell lines MDA-MB-231, A549, HeLa, MIA PaCa-2, RPMI 7951, and PC-3. Compound 4j with 2,4-dichloro substitution on the pendant phenyl ring exhibited the highest broad-spectrum cytotoxicity towards all tested cancer cell lines. Compounds 4e, 4f, 4j, 4k, 4m were further selected to study the mechanism of cellular toxicity using the triple-negative breast cancer cells MDA-MB-231. Compounds 4e, 4f, 4j, 4k, 4m induced accumulation of the treated MDA-MB-231 cells in the S phase and 4k additionally in the G2/M phase of the cell cycle. Compounds 4e, 4f, 4j, 4k, 4m induced dissipation of mitochondrial transmembrane potential and activation of caspase 3/7 in MDA-MB-231 cells with 4j being one of the most active. In an in vivo model, compound 4j and less efficiently 4e and 4f inhibited growth and proliferation and triggered DNA fragmentation in MDA-MB-231 xenografts grown on chick chorioallantoic membranes. SAR study confirmed that the 2,4-dichloro substitution pattern on the pendant phenyl ring enhanced the cytotoxic activity of benzochromene.

An Affinity-Based, Cysteine-Specific ATP Analog for Kinase-Catalyzed Crosslinking.

Kinases mediate cell signaling pathways by catalyzing protein phosphorylation. Irregularities in kinase activity are directly associated with disease conditions. Therefore, methods to identify substrates of a particular kinase are needed to understand signaling cascades in normal and diseased states. Photocrosslinking ATP analogs provide powerful tools to study kinases by covalently linking kinases with substrates. However, the involvement of UV light and nonspecific reactivity of current ATP-photocrosslinkers challenge kinase-substrate identification. We report here an affinity-based crosslinking ATP analog, ATP-methylacrylamide (ATP-MAc), that contains a cysteine-reactive acrylamide crosslinking group, which avoids the UV irradiation and non-specific reactivity of prior analogs. Using in vitro kinase assays, ATP-MAc acts as a kinase co-substrate and covalently crosslinks only kinases containing cysteines in the active site. ATP-MAc was also able to crosslink cellular proteins in lysates, documenting compatibility with cell-based studies.

A proficient microwave synthesis with structure elucidation and the exploitation of the biological behavior of the newly halogenated 3-amino-1H-benzo[f]chromene molecules, targeting dual inhibition of topoisomerase II and microtubules.

In our endeavors to develop novel and powerful agents with antiproliferative activities, a series of ß-enamionitriles, linked to the 8-bromo-1H-benzo[f]chromene moieties (4a-m), was designed and synthesized under microwave irradiation conditions. The structures of the target compounds were established on the basis of their spectral data: IR, 1H NMR, 13C NMR, 13C NMR-DEPT/APT, 19F NMR and MS. Furthermore, the antiproliferative properties were evaluated against the human cancer cell lines MCF-7, HCT-116, and HepG-2 in comparison to the positive controls Vinblastine and Doxorubicin, employing the viability assay. The obtained results confirmed that most of the tested molecules revealed strong and selective cytotoxic activities against the three cancer cell lines. The most potent cytotoxic compounds 4b, 4d, 4e, 4i, and 4k were elected for further examination, such as the cell cycle analysis, the apoptosis assay, the Caspase production, and the DNA fragmentation. This study also revealed that the desired compounds stimulate cell cycle arrest at the G2/M phases, increase the production of Caspases 3, 8, and 9, and finally cause intrinsic and extrinsic apoptotic cell death. Moreover, these compounds suppress the action of the topoisomerase II enzyme and also disrupt the microtubule functions. The SAR study of the synthesized compounds verified that the substitution on the phenyl ring of the 1H-benzo[f]chromene nucleus, accompanied with the presence of the bromine atom at the 8-position, increases the ability of these molecules against different cell lines.

Targeted potent antimicrobial benzochromene-based analogues: Synthesis, computational studies, and inhibitory effect against 14α-Demethylase and DNA Gyrase.

7H-Benzo[7,8]chromeno[2,3-d]pyrimidin-9(8H)-amine (6a,b) have been synthesized via hydrazinolysis of the imidates (5a,b). Polysubstituted chromenotriazolopyrimidine (7a-j), (12a,b) and Schiff base (8a,b) derivatives have also been prepared. The new heterocyclic derivatives were affirmed by spectral data. The target compounds have been screened for antibacterial and antifungal activity. Compounds 6a,b and 7a-c, g,h displayed the most favorable antimicrobial activities in resemblance to the reference antimicrobial agents by IZ range over 24 mm. In addition, MIC, MBC and MFC were also tested and screen for most active compound 6a by 6.25 µg/mL showing bactericidal effect. SAR study revealed that the antimicrobial vitality of the target compounds was safely influenced by the lipophilicity substituents and the calculated log P value. The potent compounds were subjected into in vitro enzyme screening (14α-Demethylase and DNA Gyrase) against both interesting targets and showed good inhibitory profile. Molecular modeling analyses were introduced and discussed focusing on the docking of active compounds into two essential targets, and their ADMET properties were studied.

Microwave synthesis of novel halogenated ß-enaminonitriles linked 9-bromo-1H-benzo[f]chromene moieties: Induces cell cycle arrest and apoptosis in human cancer cells via dual inhibition of topoisomerase I and II.

A novel series of halogenated ß-enaminonitriles (4a-m), linked 9-bromo-1H-benzo[f]-hromene moieties, were synthesized via microwave irradiation and were predestined for their cytotoxic activity versus three cancer cell lines, namely: MCF-7, HCT-116, and HepG-2. Several of the tested compounds showed high growth inhibitory activities versus the tumor cell lines. Particularly, compounds 4c, 4d, 4f, 4h, 4j, 4l, and 4m demonstrated superior antitumor activities against the aforementioned cell lines. Moreover, the apoptosis process in all the tested cells was induced by compounds 4c, 4d, 4h, 4l, and 4m, as observed by the Annexin V/PI double staining flow cytometric assay. The DNA flow, cytometric analysis revealed that these compounds prompted cell cycle arrest at the G2/M phases. Furthermore, the topoisomerase catalytic activity assays indicated that these compounds inhibited both the topoisomerase I and II enzymes.

Antiproliferative effect, cell cycle arrest and apoptosis generation of novel synthesized anticancer heterocyclic derivatives based 4H-benzo[h]chromene.

Novel ß-enaminonitrile/ester compounds (4, 6) and an imidate of 4 (9) were utilized as key scaffolds for the synthesis of newly 2-substituted 4H-benzo[h]chromene (7, 8, 10, 11, 13, 14) and 7H-benzo[h]chromeno[2,3-d]pyrimidine derivatives (15-19). The spectral data confirmed the successful isolation of the desired compounds. The targeted compounds were assessed for their in vitro anticancer activity against mammary gland breast cancer cell line (MCF-7), human colon cancer (HCT-116), and liver cancer (HepG-2), while doxorubicin, vinblastine, and colchicine were utilized as standard references drugs. Some of the examined compounds displayed high growth inhibitory activity against the three different cell lines. For example, the aminoimino derivative (18) exhibited excellent antitumor activity versus all cancer cell lines with IC50 values = 0.45 µg/mL, 0.7 µg/mL, and 1.7 µg/mL. Among the tested molecules, compounds 9, 15, and 18 were selected for further study regarding their effects on cell cycle analysis, apoptosis assay, caspase 3/7 activity, and DNA fragmentation. We found that these three potent cytotoxic compounds induce cell cycle arrest at the S and G2/M phases, which causes apoptosis. Furthermore, these compounds significantly inhibit the invasion and migration of the different tested cancer cells. Finally, the SAR survey highlighted the antitumor activity of the new molecules that was remarkably influenced by the hydrophilicity of substituent as well the fused rings at certain positions.