Synthesis, molecular modeling simulations and anticancer activity of some new Imidazo[2,1-b]thiazole analogues as EGFR/HER2 and DHFR inhibitors.

New imidazo[2,1-b]thiazole analogs were designed, synthesized, and biologically evaluated as anticancer agents. In vitro biological evaluation of the anticancer properties of the compounds was performed against different cancer cell lines. Compounds 23 and 39 showed remarkable broad -spectrum cytotoxic potency on most of the tested cell lines. Compounds 23 and 39 exhibited potent activity against the MCF-7 breast cancer cell line, with IC50 values of 1.81 and 4.95 µM, respectively, compared to DOX and SOR (IC50 values of 4.17 and 7.26 µM, respectively). An enzyme inhibition assay was carried out to clarify the possible mode of action of the tested compounds. Compounds 23 and 39 were identified as possible EGFR, HER-2, and DHFR inhibitors. Cell cycle arrest results indicated that compound 23 caused cell cycle arrest at the G0/G1 phase in the MCF-7 cells and at the G2/M phase in the Hep G2 cells. Compound 39 induced cell cycle arrest at the G2/M phase in Hela cells. In vivo testing of the anticancer activity of the two most promising molecules in this study was conducted, and the results indicated that they possess considerable in vivo anticancer activity in mice. Data obtained from the molecular modeling simulation study were consistent with the biological evaluation results.

Petroleum wastewater: Environmental protection, treatment, and safe reuse: An overview.

Oil petroleum production consumes about 1.0-7.2 bbl. The needed water for such production ranges between 0.47 and 7.2 L water to 1.0 L crude. Between 80 and 90% of the consumed water is disposed of as wasted effluents. Consequently, there is an important connection between petroleum production and the contamination of the environment and surface water in addition to their ecotoxicological effects. The objective of the present review is to through light on the hazardous impact of petroleum wastewater on the environment and water ways. The present study presents several wastewater treatment technologies in handling the petroleum produced water (PPW) and reducing the hazardous impact to the environment. Safe reuse is also presented including simple, advanced, and environmentally friendly techniques. The reported treatment technologies are divided into five main categories: membrane technologies, biological treatment processes, electro-chemical coagulation, physical/chemical treatment processes (dissolved air flotation (DAF)/air flotation (IAF), adsorption, and chemical flocculation), and catalytic oxidation including chemicals such as advanced and Fenton oxidation processes (AOPs). The analysis and observation of each treatment process are also presented. Implementing of these processes in sequential and/or in combined to avoid the drawbacks of any poor treatment are discussed. The present review discusses; also, in detail each of these treatment technologies and their efficiency including the observation and conclusions of each one. The study shows; also; how the final treated effluent can be reused for non-potable purposes as an additional water resource according to the degree of decontamination. An additional advantage of treatment is protection of both the environment and the water ways by avoiding any discharge of such hazardous wastewater.

Multi-targeted anti-Alzheimer's agents: Synthesis, biological evaluation, and molecular modeling study of some pyrazolopyridine hybrids.

A new series of compounds bearing a pyrazolopyridine scaffold was synthesized as integrated anti-Alzheimer's disease (AD) multi-targeted ligands. Compounds 49 and 51 showed remarkable activity as hAChE inhibitors with IC50 values of 0.17 and 0.16 µM, respectively; and proved to be active hBuChE inhibitors with IC50 values 0.17 and 0.69 µM, eight and two-fold more active than the reference compound rivastigmine, respectively. Compounds 49 and 51 showed potent GSK3ß inhibition with IC50 values of 0.21 and 0.26 µM, respectively compared to L807mts. Also, 49 and 51 showed 66.0 and 60.0% as tau protein aggregation inhibitors; and Aß1-42 self-aggregation inhibitors with 79.0 and 75.0% respectively. Furthermore, 49 and 51 could bind virtually with the PAS affecting Aß aggregation, thus preventing Aß-dependent neurotoxicity. They proved to have the ability to chelate bio-metals such as Fe2+, Cu2+, and Zn2+ preventing their oxidative damage in the brain of AD patients, in addition to their safety upon WI-38 cell line. Both compounds could virtually penetrate BBB and obeyed Lipinski's rule of five. Compounds 49 and 51 could be considered as MTDLs for AD patients and the obtained model and pattern of substitution could be used for further development of new multi-targeted anti-Alzheimer's agents.

Silver diamine fluoride: A stem cell cytotoxicity and dentin growth factor release in-vitro study.

AIM: To investigate the effect of 38% SDF and its serial dilutions on the Stem cells from Human Exfoliated Deciduous teeth (SHED) and its ability to release growth factors from deciduous dentine. METHODS: The viability of SHED post-exposure to 38%, 3.8%, 0.38%, 0.038%, and 0.0038% SDF were assessed at 2, 5, and 7 days using the CyQuant assay, and results were validated using the MTT assay. The osteogenic differentiation of the cells was also investigated post-exposure to 0.0038% SDF. The release of the growth factors; TGF-ß1, FGF-b, BMP-2, and VEGF from deciduous dentin discs exposed to 38% SDF, 0.0038% SDF, Ca(OH)2, MTA, and 17% EDTA were examined using ELISA. Statistical analysis was performed using means and standard deviations (p < 0.05). Two-way ANOVA compared the means of more than two groups with Tukey's multiple comparison test. The unpaired t-test was also used to compare the differences between the two data sets. CONCLUSION: 38% SDF released dentinogenic growth factors from dentin discs, potentially explaining its role in reactionary dentinogenesis. Moreover, 0.0038% SDF resulted in a non-cytotoxic concentration that enhanced cellular proliferation and released bioactive molecules from dentin comparable to the 38% concentration. After further investigations, the 0.0038% dilution of SDF could present itself as a clinical concentration.

Hall technique versus conventional preformed metal crowns: can paediatric dentists tell the difference on radiographs?

PURPOSE: Hall technique (HT) preformed metal crowns (PMCs) are allegedly oversized compared to conventional (C) PMCs. To investigate paediatric dentists' (PDs) perception of HT-PMCs and perception/ability to identify HT or C-PMCs on bitewings radiographs. METHODS: An online cross-sectional questionnaire including ten bitewings (five of each of HT/CPMCs) was sent to PDs across the globe. A PMC type score (from '10') was calculated. T test, Pearson's and Fischer's Chi-square, and Odd Ratios (OR) (p < 0.05). RESULTS: A total of 476 PDs from around the world responded. Most (97%) used PMCs in their practice. Most (98.7%) knew of, and 79% used HT-PMCs. A clear opinion shift, towards supporting HT, over time was noted (OR 11.154 [95% confidence interval (CI) 6.006-20.715]. A majority (67%) thought that HT/C-PMCs were similar radiographically. Only five PMCs were identified correctly [mean score 4.9 (± 1.73)]. A minority who thought that HT/C-PMCs were dissimilar scored higher than those who thought they were similar (5.31 ± 1.22; 4.68 ± 1.9, respectively, p < 0.00001). Nobody identified all ten PMCs. HT-PMCs were 4.63 times more identifiable than C-PMCs [(OR 24.857 CI 15.059-41.028) and (OR 5.361 CI 3.089-9.304)] for HT-PMCs and CP-MCs, respectively (p < 0.0001). CONCLUSIONS: PDs identified the PMC type in half of the bitewings. They perceived no clear radiographic difference between HT-PMCs and C-PMCs, but their chance of recognizing HT-PMCs was five times higher than C-PMCs. HT-PMC support was high.

Discovery of new pyridine heterocyclic hybrids; design, synthesis, dynamic simulations, and in vitro and in vivo breast cancer biological assays.

Pyridine is a nitrogen bearing heterocyclic scaffold that shows a wide range of biological activities. The pyridine nucleus has become an interesting target for medicinal chemistry researchers worldwide. Several pyridine derivatives exhibited good anticancer effects against diverse cell lines. Therefore, to explore new anticancer pyridine entities, novel pyridine derivatives were designed and synthesized and evaluated for their anticancer abilities in vitro and in vivo. All of the target compounds were evaluated against three different human cancer cell lines (Huh-7, A549 and MCF-7) via MTT assay. Most of the compounds exhibited significant cytotoxic activities. Compounds 3a, 3b, 5a and 5b showed superior antiproliferative activities to Taxol. Where, compound 3b showed IC50 values of 6.54, 15.54 and 6.13 µM compared to Taxol (6.68, 38.05, 12.32 µM) against Huh-7, A549 and MCF-7, respectively. Also, tubulin polymerization assay was carried out. The most potent compounds 3a, 3b, 5a and 5b could significantly inhibit tubulin polymerization with IC50 values of 15.6, 4.03, 6.06 and 12.61 µM, respectively. Compound 3b exhibited the highest tubulin polymerization inhibitory effect with an IC50 value of 4.03 µM compared to combretastatin (A-4) (1.64 µM). Molecular modeling studies of the designed compounds confirmed that most of the compounds made the essential binding interactions compared to the reference compound which assisted in the prediction of the structure requirements for the detected anticancer activity. Finally, in vivo studies showed that compound 3b could significantly inhibit breast cancer.

Hydrazinecarbonyl-thiazol-2-acetamides with pronounced apoptotic behavior: synthesis, in vitro/in vivo anti-proliferative activity and molecular modeling simulations.

A new series of N-[4-(2-substituted hydrazine-1-carbonyl)thiazole-2-yl]acetamides was synthesized and evaluated in vitro against six human cell lines as antitumor agents. Compounds 20, 21 and 22 showed remarkable inhibition to HeLa (IC50 values of 1.67, 3.81, 7.92 µM) and MCF-7 (IC50 values of 4.87, 5.81, 8.36 µM, respectively) cell growth with high selectivity indices and safety profiles. Compound 20 showed significant decreases in both tumor volume and body weight gain compared to vehicle control, in the solid tumor animal model of Ehrlich ascites carcinoma (EAC) with recovered caspase-3 immuno-expression. Flow cytometry cell analysis showed that 20 exerts anti-proliferative activity in mutant Hela and MCF-7 cell lines through arresting the cell growth at the G1/S phase producing cell death via apoptosis rather than necrosis. To explain the antitumor mode of action of the most active compounds, EGFR-TK and DHFR inhibition assays were carried out. Compound 21 conveyed dual EGFR/DHFR inhibition with IC50 0.143 (EGFR) and 0.159 (DHFR) µM. Compound 20 showed DHFR inhibition with IC50 0.262 µM. Compound 22 exhibited the best EGFR inhibitory efficacy with IC50 0.131 µM. Molecular modelling study revealed that 21 and 22 have binding interactions with EGFR amino acid residues Lys745 and Asp855. Compounds 20 and 21 showed affinity toward DHFR amino acid residues Asn64, Ser59 and Phe31. The ADMET profile and Lipinski's rule of five calculated for these compounds were acceptable. Compounds 20, 21 and 22 could be regarded as promising prototype antitumor agents for further optimization.

New quinazolinone-based derivatives as DHFR/EGFR-TK inhibitors: Synthesis, molecular modeling simulations, and anticancer activity.

New 2-mercapto-quinazolin-4-one analogs were synthesized and tested for their in vitro anticancer activity, dihydrofolate reductase (DHFR) inhibition, and epidermal growth factor tyrosine kinase (EGFR-TK) inhibition activities. Compound 24, which is characterized by a 2-benzyl-thio function, showed broad-spectrum anticancer activity with high safety profile and selectivity index. The concentrations of 24 causing 50% growth inhibition (GI50 ) and total cell growth inhibition (TGI) and its lethal concentration 50 (LC50 ) were 15.1, 52.5, and 91.2 µM, respectively, using 5-fluorouracil as a positive control. Also, it showed EGFR-TK inhibitory activity with IC50 = 13.40 nM compared to gefitinib (IC50 = 18.14 nM) and DHFR inhibitory potency with 0.30 µM compared to methotrexate (MTX; IC50 = 0.08 µM). In addition, compound 24 caused cell cycle arrest and apoptosis on COLO-205 colon cancer cells. Compounds 37, 21, and 54 showed remarkable DHFR inhibitory activity with IC50 values of 0.03, 0.08, and 0.08 µM, respectively. The inhibitory properties of these compounds are due to an electron-withdrawing group on the quinazolinone ring, except for compound 54. In a molecular modeling study, compound 24 showed the same binding mode as gefitinib as it interacted with the amino acid Lys745 via π-π interaction. Compound 37 showed a similar binding mode as MTX through the binding interaction with Lys68, Asn64 via hydrogen bond acceptor, and Phe31 via arene-arene interaction. The obtained model and substitution pattern could be used for further development.

New thiazole-based derivatives as EGFR/HER2 and DHFR inhibitors: Synthesis, molecular modeling simulations and anticancer activity.

New series of thiazole and imidazo[2,1-b]thiazole derivatives were synthesized and tested for their in vitro anticancer activity. Compounds 27, 34, 39 and 42-44 showed the best anticancer activity against the tested cancer cell lines with high safety profile and selectivity indices, especially MCF-7 breast cancer, compared to sorafenib. As an attempt to reveal their mode of cytotoxicity, EGFR, HER2 kinase and DHFR inhibition assays were performed. Compounds 39 and 43 were the most potent dual EGFR/HER2 kinase inhibitors, with IC50 values of 0.153 (EGFR), 0.108 (HER2) and 0.122 (EGFR), 0.078 (HER2) µM, respectively. 39 and 42 were the best DHFR inhibitors showing IC50 0.291 and 0.123 µM, respectively. 39 and 43 induced their cytotoxicity via cell cycle arrest at G1/S and G1 phases, respectively, and apoptosis rather than necrosis in the MCF-7 breast cancer cell line. In vivo anti-breast cancer assay of 39 and 43 showed significant tumor volume reduction with recovered caspase-3 immunoexpression. Modeling study results proved the importance of the 5-(4-substituted phenyl)-imidazo[2,1-b]thiazole moiety and the hydrazide side chain for the anticancer activity. The most potent compounds showed good drug-likeness features and could be used as prototypes for further optimization. 39 could be an example of a multi-targeting anticancer agent that acts by inhibiting EGFR/HER2 kinase, DHFR enzymes and cellular apoptosis.

Taguchi Approach for Optimization of a Green Quantitative 1H-NMR Practice for Characterization of Levetiracetam and Brivaracetam in Pharmaceuticals.

BACKGROUND: Recently, quantitative nuclear magnetic resonance (qNMR) competes with separation techniques such as high performance liquid chromatography (HPLC) and capillary electrophoresis for quantification purposes when dealing with molecules that lack a chromophore. OBJECTIVE: The advantages of the proton nuclear magnetic resonance spectroscopy as a revolutionary quantitative analysis method were exploited aimed at simple and green assessment of two racetams, namely levetiracetam (LEV) and brivaracetam (BRV), as a new family of antiepileptic medications with a unique mechanism of action. The developed technique was effectively used to determine LEV in Keppra tablets and BRV in laboratory-prepared tablets without interfering with the ordinarily suspected excipients. METHOD: A Taguchi approach was applied as a powerful and user-friendly statistical technique for optimization of the qH1NMR experimental design for both drugs. The optimum acquisition conditions were number of scans 32, pulse angle 20°, and relaxation delay of 40 s for LEV and number of scans 128, pulse angle 90°, and relaxation delay of 1 s for BRV. NMR spectra were obtained by means of phloroglucinol as an internal standard and dimethyl sulfoxide-d6 as a solvent. RESULTS: The diagnostic doublet of doublet quantitative signals at 4.3 and at 4.2 ppm were chosen to estimate LEV and BRV, respectively. The recovery of both drugs was quantified through the range of 0.1-12 mg/mL. The limits of detection were 0.013, 0.0013 and the limits of quantitation were 0.04, 0.0039 mg/mL for LEV and BRV correspondingly. CONCLUSIONS: The suggested technique was fully validated according to ICH guidelines and proved to be an eco-friendly practice by means of three different assessment tools, including the green analytical procedures index, national environmental methods index, and analytical eco-scale. qH1NMR should be considered a green alternative for quantification and quality control assessment of pharmaceuticals. HIGHLIGHTS: This research represents the first simple, quick, and green alternative method for determination of both racetams in their pharmaceuticals.

New phthalimide-based derivatives as EGFR-TK inhibitors: Synthesis, biological evaluation, and molecular modeling study.

A novel series of phthalimide derivatives was synthesized and evaluated for in vitro antitumor activity against six human cancer cell lines; HepG-2, HCT-116, MCF-7, Hep2, PC3 and Hela.The obtained results revealed that compound 32 was the most potent antitumor, while compounds 33, 22 and 24 showed strong activity against all tested cell lines. Further biological evaluation of the most active compounds was done and their in vitro EGFR-TK inhibition was tested, and the results came in accordance with the results of antitumor testing, where 32 displayed promising inhibitory activity (IC50 = 0.065 µM) compared to the standard drug erlotinib (IC50 = 0.067 µM). In addition, compounds 48, 22, 28 and 19 showed strong inhibitory activity (IC50 = 0.089, 0.093, 0.147 and 0.152 µM respectively). Cell cycle analysis was conducted and the results revealed that 32 induced cell cycle arrest on Hela and MCF-7 at G0-G1 phase and Pre-G1 phase causing cell death mainly via apoptosis. Additionally, in vivo antitumor screening revealed that 32 reduced both body weight and tumor volume in solid tumor utilizing Ehrlich ascites carcinoma (EAC) animal model. Molecular modeling study showed that 32 and 48 have the highest affinity for binding with the active site of EGFR-TK with docking score comparable to erlotinib. Compounds 32 and 48 could be used as template models for further optimization.

Thiazole-based SARS-CoV-2 protease (COV Mpro ) inhibitors: Design, synthesis, enzyme inhibition, and molecular modeling simulations.

As an attempt to contribute to the efforts of combating the pandemic virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for COVID-19, new analogs of the repurposed drug nitazoxanide which showed promising inhibitory efficacy on a viral protease enzyme were designed, synthesized and evaluated for their inhibitory activity on the main protease of the SARS-CoV-2 virus, using the COV2-3CL protease inhibition assay. The obtained results showed that the N-(substituted-thiazol-2-yl)cinnamamide analogs 19, 20, and 21 were the most active compounds with IC50 values of 22.61, 14.7, 21.99 µM, respectively, against the viral protease compared to the reference drugs, nitazoxanide, and lopinavir. Molecular modeling studies showed binding interactions of 19, 20, and 21 with hydrogen bonds to Gln189 and Glu166, arene-arene interaction between the thiazole moiety and His41, and other hydrophobic interactions between the ethene spacer moiety and Asn142. Moreover, an extra arene-arene interaction between substituted benzo[d]thiazole and His41 was observed regarding compounds 19 and 21. Surface mapping and flexible alignment proved the structural similarity between the new drug candidates and nitazoxanide. Compliance of the new compounds to Lipinski's rule of five was investigated and absorption, distribution, metabolism, excretion, and toxicology data were predicted. The newly synthesized compounds are promising template ligands for further development and optimization.

Ameliorative Effect of Oxytocin on FBN1 and PEPCK Gene Expression, and Behavioral Patterns in Rats' Obesity-Induced Diabetes.

Amelioration of hyperinsulinemia and insulin resistance associated with obesity is a cardinal target for therapeutics. Therefore, we investigated the relation of Fibrilln-1 (FBN1) mRNA expression and hepatic phosphoenolpyruvate caboxykinase (PEPCK) enzyme to the ameliorative impact of oxytocin on obesity-induced diabetes, suggesting glycogenolysis markers in diabetic models. Four groups of forty male Wistar rats were formed (n = 10): a control group fed basal diet and intraperitoneal injections of saline; an oxytocin-injected group; a diet-induced obese group fed a high-fat/high-sugar diet and injected with saline; a diet-induced obese group injected with oxytocin. Depending on blood glucose levels, obese groups were further sub-grouped into prediabetic, and diabetic rats, with 5 rats each, at the ninth and the 16th week of the feeding period, respectively. FBN1 expression and PEPCK activity were determined using the qPCR technique and some biochemical parameters (glycemic, lipid profile, kidney, and liver functions) were determined using kits. Obese groups showed an elevation of brain FBN1 expression, high serum lipid profile, high glucose level, and a deleterious impact on liver and kidney functions. Obese groups showed the stimulator effect of the PEPCK enzyme and time-dependent pathological changes in renal and hepatic tissues. The motor activities were negatively correlated with FBN1 gene expression in prediabetic and diabetic rats. In addition to our previous review of the crucial role of asprosin, here we showed that oxytocin could ameliorate obesity-induced diabetes and decrease FBN1 gene expression centrally to block appetite. Oxytocin caused decreases in PEPCK enzyme activity as well as glycogenolysis in the liver. Therefore, oxytocin has a potential effect on FBN1 expression and PEPCK enzyme activity in the obesity-induced diabetic-rat model.

Sleep-disordered breathing in children and adolescents seeking paediatric dental care in Dubai, UAE.

PURPOSE: This study aimed to evaluate the severity of high-risk SDB in children and adolescents seeking paediatric dental care. Sleep-disordered breathing (SDB) has many untoward consequences that may interfere with children's health and is associated with several risk factors. METHODS: In this cross-sectional study, the convenience sample included 65 healthy children and adolescents aged 7-16. High-risk SDB breathing was assessed using the Paediatric-Sleep-Questionnaire consisting of 22 questions. High-risk was defined as a positive response to 33% or more of the questions. The clinical examination included: tonsils' size, Body-Mass Index, orthodontic examination, and enamel defects. RESULTS: In this sample of 65 children with a mean age of 9.75 (± 2.60) years; 36 (55.4%) were boys, and 29 (44.6%) were girls. Overall, 12.3% of children in the sample were at high-risk of SDB, and this was significantly associated with tonsils' size (P = 0.001), Body-Mass Index (P = 0.03), Class-II molar relationship (P = 0.03), and posterior crossbite/s (P = 0.02). CONCLUSIONS: This study suggested that approximately 12% of the sample studied were potentially at risk of SDB. Tonsils' size, Body-Mass Index, Class-II molar relationship, and posterior crossbite/s were positively associated with the risk of SDB. Therefore, the importance of investigating the risk for sleep-disordered breathing should not be disregarded.

Synthesis, biological evaluation, and molecular modeling simulations of new heterocyclic hybrids as multi-targeted anti-Alzheimer's agents.

The widespread and the recognition of the multifactorial nature of Alzheimer disease (AD) increased the demands for multi-targeted directed ligands (MTDLs) to overcome possible drug-drug interactions of the combination therapy, and to acquire superior therapeutic profile than single targeted molecules. Two main scaffolds namely: pyrazolopyridine and tetrahydroacridine (THA) were used to synthesize four different series of integrated multi-targeted synthons possessing ChE (hAChE or hBuChE), Aß1-42 aggregation inhibition potency, in addition to optimum metal chelating capability. Structure modifications were performed to 9-amino function of THA core of tacrine and the pyrazolopyridine scaffolds linked to a variety of cyclic secondary amines directly or using amide spacers or ethylamine bridge or engaging THA with pyrazolopyridine to produce hybrid compounds. Different 9-amino substitutions improved the in vitro hAChE activity of 7- or 6,7-disubstituted THA derivatives. Compounds 16 and 28 proved to be multimodal anti-AD agents as they were potent hAChE inhibitors, in addition, they could bind with the amino acids of the peripheral anionic site (PAS) affecting Aß aggregation and hence Aß-dependent neurotoxicity especially compound 16 which was almost twofold more active than donepezil. Furthermore, both compounds directly inhibited Aß1-42 self-aggregation and chelated bio-metals such as Fe2+, Zn2+ and Cu2+ preventing reactive oxygen species (ROS) generation by Aß and its oxidative damage in the brain regions of AD patients. Compound 28 had superior privilege by its dual ChE activity resulting in better cognitive improvement. Compounds 16 and 28 showed acceptable relative safety upon hepG2 cell line and excellent BBB penetration with wide safety margin as their LD50 were higher than 120 mg/kg.

Oxoanion Imprinting Combining Cationic and Urea Binding Groups: A Potent Glyphosate Adsorber.

The use of polymerizable hosts in anion imprinting has led to powerful receptors with high oxyanion affinity and specificity in both aqueous and non-aqueous environments. As demonstrated in previous reports, a carefully tuned combination of orthogonally interacting binding groups, for example, positively charged and neutral hydrogen bonding monomers, allows receptors to be constructed for use in either organic or aqueous environments, in spite of the polymer being prepared in non-competitive solvent systems. We here report on a detailed experimental design of phenylphosphonic and benzoic acid-imprinted polymer libraries prepared using either urea- or thiourea-based host monomers in the presence or absence of cationic comonomers for charge-assisted anion recognition. A comparison of hydrophobic and hydrophilic crosslinking monomers allowed optimum conditions to be identified for oxyanion binding in non-aqueous, fully aqueous, or high-salt media. This showed that recognition improved with the water content for thiourea-based molecularly imprinted polymers (MIPs) based on hydrophobic EGDMA with an opposite behavior shown by the polymers prepared using the more hydrophilic crosslinker PETA. While the affinity of thiourea-based MIPs increased with the water content, the opposite was observed for the oxourea counterparts. Binding to the latter could however be enhanced by raising the pH or by the introduction of cationic amine- or Na+-complexing crown ether-based comonomers. Use of high-salt media as expected suppressed the amine-based charge assistance, whereas it enhanced the effect of the crown ether function. Use of the optimized receptors for removing the ubiquitous pesticide glyphosate from urine finally demonstrated their practical utility.