ELECTROCHEMICAL AND CHEMOMETRIC DETERMINATION OF DORZOLAMIDE AND TIMOLOL IN EYE DROPS USING MODIFIED MULTIWALL CARBON NANOTUBE ELECTRODE

Objective: This work is focused on the construction of simple and sensitive electrochemical sensor for quantitative determination of dorzolamide (DOR) and timolol maleate (TIM). This method is based on the incorporation of multiwall carbon nanotubes (MWCNT) into the carbon paste electrode which improve the characteristics of the electrode.Methods: The electrochemical response of modified electrode was based on voltammetric oxidation, using cyclic voltammetry (CV) and impedance spectroscopy (EIS). The structural morphology of the surface modified electrode was characterized by scanning electron microscope (SEM). Quantitative analysis for each of the two compounds in a mixture has been examined by using of chemometric tools for resolving overlapping signals. The prediction performance of the chemometric method was analyzed by principal component regression (PCR) and partial least square (PLS).Results: Fractional factorial design was constructed from set of synthetic mixtures of two drugs in concentration ranges of 0.05 to 1.6µg/ml for DOR and 1.5-20 µg/ml for TIM. Under optimum experimental conditions, DOR and TIM gave rectilinear response over the concentration range of 0.072-1.88 µg/ml and 1.16-20.84 µg/ml, respectively. The limit of detection (LOD) was found to be 0.098 and 1.025 µg/ml, for DOR and TIM, respectively. It found that the % of relative prediction error (RPE) was acceptable and satisfactory.Conclusion: In these work, for the first time, a new voltammetric simultaneous method developed for a rapid and efficient determination of DOR and TIM from eye dropper sample at nano modified electrode with satisfactory results. These results indicate that MWCNT holds great promise in practical application

Stereoselective synthesis and X-ray structure determination of novel 1,2-dihydroquinolinehydrazonopropanoate derivatives

A novel series of 1,2-dihydroquinolinhydrazonopropanoate have been synthesized via a convenient aza-Michael addition reaction between hydrazinylquinolinones and ethyl propiolate in ethanol under refluxing temperature. The structures for all obtained products were confirmed with FTIR, NMR spectrums, as well as mass spectrometry. In addition, the monoclinic structure for compounds 8a, 8c, and 8d was also confirmed via X-ray crystallography analyses. The E-configuration for the obtained products was confirmed form the X-ray analysis. On the other hand, the crystal packing shows that the intermolecular and hydrogen bonds between atoms are parallel to the bc plan

Synthesis, Antioxidant and Antiproliferative Actions of 4-(1,2,3-Triazol-1-yl)quinolin-2(1H)-ones as Multi-Target Inhibitors

The reaction of 4-azido-quinolin-2(1H)-ones 1a–e with the active methylene compounds pentane-2,4-dione (2a), 1,3-diphenylpropane-1,3-dione (2b), and K$_2$CO$_3$ was investigated in this study. This approach afforded 4-(1,2,3-triazol-1-yl)quinolin-2(1H)-ones 3a–j in high yields and purity. All newly synthesized products’ structures were identified. Compounds 3a–j were tested for antiproliferative activity against a panel of four cancer cell lines. In comparison to the reference erlotinib (GI$_{50}$ = 33), compounds 3f–j were the most potent derivatives, with GI$_{50}$ values ranging from 22 nM to 31 nM. The most effective antiproliferative derivatives, 3f–j, were subsequently investigated as possible multi-target inhibitors of EGFR, BRAF$^{V600E}$, and EGFR$^{T790M}$. Compound 3h was the most potent inhibitor of the studied molecular targets, with IC50 values of 57 nM, 68 nM, and 9.70 nM, respectively. The apoptotic assay results demonstrated that compounds 3g and 3h function as caspase-3, 8, and Bax activators as well as down-regulators of the antiapoptotic Bcl2, and hence can be classified as apoptotic inducers. Finally, compounds 3g and 3h displayed promising antioxidant activity at 10 µM, with DPPH radical scavenging of 70.6% and 73.5%, respectively, compared to Trolox (77.6%)

Fasciola gigantica Fatty Acid Binding Protein (FABP) as a Prophylactic Agent against Schistosoma mansoni Infection in CD1 Mice

Although schistosomicidal drugs and other control measures exist, the advent of an efficacious vaccine remains the most potentially powerful means for controlling this disease. In this study, native fatty acid binding protein (FABP) from Fasciola gigantica was purified from the adult worm's crude extract by saturation with ammonium sulphate followed by separation on DEAE-Sephadex A-50 anion exchange chromatography and gel filtration using Sephacryl HR-100, respectively. CD1 mice were immunized with the purified, native F. gigantica FABP in Freund's adjuvant and challenged subcutaneously with 120 Schistosoma mansoni cercariae. Immunization of CD1 mice with F. gigantica FABP has induced heterologous protection against S. mansoni, evidenced by the significant reduction in mean worm burden (72.3%), liver and intestinal egg counts (81.3% and 80.8%, respectively), and hepatic granuloma counts (42%). Also, it elicited mixed IgG1/IgG2b immune responses with predominant IgG1 isotype, suggesting that native F. gigantica FABP is mediated by a mixed Th1/Th2 response. However, it failed to induce any significant differences in the oogram pattern or in the mean granuloma diameter. This indicated that native F. gigantica FABP could be a promising vaccine candidate against S. mansoni infection

Reactivity of 2-substituted hydrazinecarbothioamides towards tetracyanoethylene and convenient synthesis of (5-amino-2-diazenylthiazolylmethylene) malononitrile derivatives

2-{Amino-[5-amino-2-(substituted diazenyl) thiazol-4-yl] methylene} malononitriles were synthesized from the reaction of 2-substituted hydrazinecarbothioamides with tetracyanoethylene (TCNE) to give tetracyanoethane adduct, followed by heterocyclization afforded the target compounds. The structure of (E)-2-{amino-[5-amino-2-(phenyldiazenyl) thiazol-4-yl] methylene} malononitrile was supported by single crystal X-ray crystallography.Peer reviewe

The Arabic Version of the Impact of Event Scale-Revised : psychometric evaluation among psychiatric patients and the general public within the context of COVID-19 outbreak and quarantine as collective traumatic events

The Coronavirus Disease-19 (COVID-19) pandemic has provoked the development of negative emotions in almost all societies since it first broke out in late 2019. The Impact of Event Scale-Revised (IES-R) is widely used to capture emotions, thoughts, and behaviors evoked by traumatic events, including COVID-19 as a collective and persistent traumatic event. However, there is less agreement on the structure of the IES-R, signifying a need for further investigation. This study aimed to evaluate the psychometric properties of the Arabic version of the IES-R among individuals in Saudi quarantine settings, psychiatric patients, and the general public during the COVID-19 outbreak. Exploratory factor analysis revealed that the items of the IES-R present five factors with eigenvalues > 1. Examination of several competing models through confirmatory factor analysis resulted in a best fit for a six-factor structure, which comprises avoidance, intrusion, numbing, hyperarousal, sleep problems, and irritability/dysphoria. Multigroup analysis supported the configural, metric, and scalar invariance of this model across groups of gender, age, and marital status. The IES-R significantly correlated with the Depression Anxiety Stress Scale-8, perceived health status, and perceived vulnerability to COVID-19, denoting good criterion validity. HTMT ratios of all the subscales were below 0.85, denoting good discriminant validity. The values of coefficient alpha in the three samples ranged between 0.90 and 0.93. In path analysis, correlated intrusion and hyperarousal had direct positive effects on avoidance, numbing, sleep, and irritability. Numbing and irritability mediated the indirect effects of intrusion and hyperarousal on sleep and avoidance. This result signifies that cognitive activation is the main factor driving the dynamics underlying the behavioral, emotional, and sleep symptoms of collective COVID-19 trauma. The findings support the robust validity of the Arabic IES-R, indicating it as a sound measure that can be applied to a wide range of traumatic experiences

Design, synthesis, crystal structures and biological evaluation of some 1,3-thiazolidin-4-ones as dual CDK2/EGFR potent inhibitors with potential apoptotic antiproliferative effects

A series of novel thiazolidine-4-one derivatives was synthesized by reacting 1,4-disubstituted hydrazine carbothioamides with diethyl azodicarboxylate. The structures were confirmed by spectroscopic data as well as single-crystal X-ray analyses. The antiproliferative activity of the synthesized compounds was investigated against four human cancer cell lines using an MTT assay. Compounds 5d, 5e, and 5f revealed the most potent antiproliferative activity with GI$_{50}$ values ranging from 0.70 µM to 1.20 µM, compared to doxorubicin GI$_{50}$ value = 1.10 µM. Compounds 5d, 5e, and 5f were further investigated for their inhibitory activities against CDK2 and EGFR as potential targets for their molecular mechanism. Compounds 5e and 5f have showed potent inhibitory activity to CDK2 enzyme with IC$_{50}$ values of 18 and 14 nM, which is more potent than the reference dinaciclib (IC$_{50}$ = 20 nM). Moreover, compounds 5e and 5f were the most potent EGFR inhibitors, with IC$_{50}$ values of 93 and 87 nM, respectively, compared to the reference erlotinib (IC$_{50}$ = 70 nM). In addition, the most potent derivatives were tested for their apoptotic activity against caspases 3, 8, and 9, and the results showed that compounds 5d, 5e, and 5f revealed a greater increase in active caspases 3,8 and 9 than doxorubicin. Also, compounds 5d, 5e, and 5f elevated cytochrome C levels in the MCF-7 human breast cancer cell line by about 15.5, 15.8, and 16.5 times, respectively. Finally, a molecular docking study was performed to investigate the binding sites of these compounds within the active sites of CDK2 and EGFR targets, and the results confirmed that the most potent CDK2 and EGFR inhibitor 5h also have showed the highest docking score

A convenient and efficient synthesis of thiazolidin-4-ones via cyclization of substituted hydrazinecarbothioamides

2-Substituted hydrazinecarbothioamides and N ,2-disubstituted hydrazinecarbothioamides react in high yield with dimethyl acetylenedicarboxylate (DMAD) to give 4-oxo-Z-(thiazolidin-5-ylidene) acetate derivatives. Several mechanistic options involving interaction are presented. The structures of thiazolidin-4-ones have been unambiguously confirmed by single crystal X-ray crystallography. (C) 2014 The Authors. Production and hosting by Elsevier B.V. on behalf of King Saud University.Peer reviewe

Design, synthesis, crystal structures and biological evaluation of some 1,3-thiazolidin-4-ones as dual CDK2/EGFR potent inhibitors with potential apoptotic antiproliferative effects

A series of novel thiazolidine-4-one derivatives was synthesized by reacting 1,4disubstituted hydrazine carbothioamides with diethyl azodicarboxylate. The structures were confirmed by spectroscopic data as well as single-crystal X-ray analyses. The antiproliferative activity of the synthesized compounds was investigated against four human cancer cell lines using an MTT assay. Compounds 5d, 5e, and 5f revealed the most potent antiproliferative activity with GI50 values ranging from 0.70 mM to 1.20 mM, compared to doxorubicin GI50 value = 1.10 mM. Compounds 5d, 5e, and 5f were further investigated for their inhibitory activities against CDK2 and EGFR as potential targets for their molecular mechanism. Compounds 5e and 5f have showed potent inhibitory activity to CDK2 enzyme with IC50 values of 18 and 14 nM, which is more potent than the reference dinaciclib (IC50 = 20 nM). Moreover, compounds 5e and 5f were the most potent EGFR inhibitors, with IC50 values of 93 and 87 nM, respectively, compared to the reference erlotinib (IC50 = 70 nM). In addition, the most potent derivatives were tested for their apoptotic activity against caspases 3, 8, and 9, and the results showed that compounds 5d, 5e, and 5f revealed a greater increase in active caspases 3,8 and 9 than doxorubicin. Also, compounds 5d, 5e, and 5f elevated cytochrome C levels in the MCF-7 human breast cancer cell line by about 15.5, 15.8, and 16.5 times, respectively. Finally, a molecular docking study was performed to investigate the binding sites of these compounds within the active sites of CDK2 and EGFR targets, and the results confirmed that the most potent CDK2 and EGFR inhibitor 5h also have showed the highest docking (c) 2022 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Peer reviewe