Synthesis, Glucosidase Inhibition, and In Silico Modeling Analysis of Highly Fluorinated 2-Imino-1,3-thiazolines in Search of Potent Antidiabetic Agents.

In the present work, 2-imino-1,3-thiazolines featuring highly fluorinated fragments were synthesized through a straightforward cyclization of diversely substituted thioureas with 2-bromo-1-(4-fluorophenyl)ethan-1-one. The target compounds were obtained in good yields, and structures were established by FTIR and 1H- and 13C NMR spectroscopic methods. The in vitro biological assay revealed that all the compounds significantly obstruct the α-glucosidase. Compound 6d (3-fluoro-N-(3-(2-fluorophenyl)-4-(4-fluorophenyl)thiazol-2(3H)-ylidene)benzamide) showed the highest antidiabetic potential with an IC50 value of 1.47 ± 0.05 µM. In addition, computational analysis revealed the binding energy of -11.1 kcal/mol for 6d which was lower than the positive standard, acarbose (-7.9 kcal/mol). Several intermolecular interactions between the active site residues and 6d highlight the significance of 2-imino-1,3-thiazoline core in attaining the potent efficacy and making these compounds a valuable pharmacophore in drug discovery.

Anticancer evaluations of iodoquinazoline substituted with allyl and/or benzyl as dual inhibitors of EGFRWT and EGFRT790M: design, synthesis, ADMET and molecular docking.

Fifteen new iodoquinazoline derivatives, 5a,b to 18, are reported in this study and their anticancer evaluation as dual inhibitors of EGFRWT and EGFRT790M. The new derivatives were designed according to the target of structural requirements of receptors. Cytotoxicity of our compounds was evaluated against MCF-7, A549, HCT116 and HepG2 cell lines using MTT assay. Compounds 18, 17 and 14b showed the highest anticancer effects with IC50 = 5.25, 6.46, 5.68 and 5.24 µM, 5.55, 6.85, 5.40 and 5.11 µM and 5.86, 7.03, 6.15 and 5.77 µM against HepG2, MCF-7, HCT116 and A549 cell lines, respectively. The eight highly effective compounds 10, 13, 14a, 14b, 15, 16, 17 and 18 were inspected against VERO normal cell lines to evaluate their cytotoxicity. Our conclusion was that compounds 10, 13, 14a, 14b, 15, 16, 17 and 18 possessed low toxicity against VERO normal cells with IC50 increasing from 43.44 to 52.11 µM. All compounds were additionally assessed for their EGFRWT and EGFRT790M inhibitory activities. Additionally, their ability to bind with EGFRWT and EGFR receptors was confirmed by molecular docking. Compound 17 exhibited the same inhibitory activity as erlotinib. Compounds 10, 13, 14b, 16 and 18 excellently inhibited VEGFR-2 activity with IC50 ranging from 0.17 to 0.50 µM. Moreover, compounds 18, 17, 14b and 16 remarkably inhibited EGFRT790M activity with IC50 = 0.25, 0.30, 0.36 and 0.40 µM respectively. As planned, compounds 18, 17 and 14b showed excellent dual EGFRWT/EGFRT790M inhibitory activities. Finally, our compounds 18, 17 and 14b displayed good in silico ADMET calculated profiles.

Diels-Alder clickable furan-thiosemicarbazide cellulose for selective ruthenium (III) imprinting.

Developing an efficient adsorbent for Ru3+ ions in wastewater is crucial for both environmental protection and resource recovery. This study introduces a novel approach using cellulose-based adsorbents, specifically modified with furan-thiosemicarbazide (FTC), to enhance their selectivity for Ru3+ ions. By cross-linking the Ru3+/FTC-modified cellulose (FTC-CE) complex with a bis(maleimido)ethane (BME) cross-linker, we created a Ru3+ ion-imprinted sorbent (Ru-II-CE) that exhibits a strong affinity and selectivity for Ru3+ ions. The synthesis process was thoroughly characterized using NMR and FTIR spectroscopy, while the surface morphology of the sorbent particles was examined with scanning electron microscopy. The Ru-II-CE sorbent demonstrated exceptional selectivity for Ru3+ among competing metal cations, achieving optimal adsorption at a pH of 5. Its adsorption capacity was notably high at 215 mg/g, fitting well with the Langmuir isotherm model, and it followed pseudo-second-order kinetics. This study highlights the potential of FTC-CE for targeted Ru3+ removal from wastewater, offering a promising solution for heavy metal decontamination.

Designing of a cellulose-based ion-imprinted biosorbent for selective removal of lead (II) from aqueous solutions.

Developing an effective adsorbent for Pb2+ removal from wastewater has huge economic and environmental implications. Adsorbents made from cellulosic materials that have been modified with certain chelators could be used to get rid of metal cations from aqueous solutions. However, their selectivity for specific metals remains very low. Here, we describe the synthesis of 4-(2-pyridyl)thiosemicarbazide (PTC) hydrazidine-functionalized cellulose (Pb-PTC-CE), a polymer imprinted with Pb2+ ions that may be used to remove Pb2+ ions from wastewater. Owing to its potent -NH2 functionalization, PTC hydrazidine not only served as an efficient chelator to effectively supply coordinating sites and construct hierarchical porous structures on Pb-PTC-CE, but it also made it possible for cross-linking to occur through the glyoxal cross-linker. The abundant chelators, along with the hierarchical porous construction of the developed Pb-PTC-CE with PTC functionality, result in a greater sorption capacity of 336 mg/g and a short sorption period of 40 min for Pb2+. Additionally, Pb-PTC-CE exhibits highly selective Pb2+ uptake compared to competing ions. This study proposes a feasible methodology for the development of high-quality materials for Pb2+ remediation by combining the advantages of active ligand functionality with ion-imprinting techniques in a straightforward way.

Development and assessment of isatin hydrazone-functionalized/ion-imprinted cellulose adsorbent for gadolinium (III) removal.

It is of tremendous economic and environmental significance to obtain a powerful adsorbent for the extraction of Gd3+ from wastewater. Adsorbents derived from cellulosic materials functionalized with specific chelators show great promise for the removal of heavy metal ions from wastewater. The selectivity of these sorbents for metal ions is, however, still rather poor. Here, we present a technique for trapping Gd3+ ions from wastewater by synthesizing Gd3+ ion-imprinted polymers based on isatinhydrazone-functionalized cellulose (Gd-ISH-CE). Not only did isatinhydrazone work as a tridentate ligand to directly provide ligand vacancies and build hierarchy pores on Gd-ISH-CE, but it also enabled cross-linking through the epichlorohydrine cross-linker thanks to its very effective NH2 functionalization. The as-prepared Gd-ISH-CE with ISH functionality shows a high adsorption capacity of 275 mg/g and a rapid equilibration time of 30 min for Gd3+ due to its plentiful binding sites and hierarchical pore structure. Furthermore, Gd-ISH-CE shows very selective capture of Gd3+ over competing ions. By integrating the benefits of ion-imprinting and chelator functionalization methodologies in an effortless manner, this study presents a practical approach to the development of superior materials for Gd3+ recovery.

Development and evaluation of thiosalicylic-modified/ion-imprinted chitosan for selective removal of cerium (III) ion.

Chitosan was used in this study as the bio-based product for the development of microparticles for the specifically targeted removal of cerium ions (Ce3+) by ion-imprinting technology. A thiosalicylic hydrazide-modified chitosan (TSCS) is produced via cyanoacetylation of chitosan, followed by hydrazidine derivatization to finally introduce the thiosalicylate chelating units. Ion-imprinted Ce-TSCS sorbent microparticles were prepared by combining the synthesized TSCS with Ce3+, crosslinking the polymeric Ce3+/TSCS complex with glutaraldehyde, and releasing the chelated Ce3+ using an eluent solution containing a mixture of EDTA and HNO3. Ce-TSCS had a capacity of 164 ± 1 mg/g and better removal selectivity for Ce3+ because it was smart enough to figure out which target ions would fit into the holes made by Ce3+ during the imprinting process. The kinetic data were well suited to a pseudo-second-order model, and the isotherms were well described by the Langmuir model, both of which pointed to chemisorption and adsorption through Ce3+ chelation. XPS and FTIR analyses demonstrate that the predominant adsorption mechanism is the coordination of Ce3+ with the -NH-, -NH2, and -SH chelating units of the thiosalicylic hydrazidine. These findings provide fresh direction for the development of sorbent materials that can effectively and selectively remove Ce3+ from aqueous effluents.

Synthesis and characterization of gellan gum-based hydrogels for drug delivery applications.

In this study, gellan gum (Gel) derivatives were allowed to interact via aqueous Diels-Alder chemistry without the need for initiators, producing a crosslinked hydrogel network that exhibited good potential as a drug carrier using tramadol as a drug model. Hydrogel conjugation was achieved by the synthesis of a maleimide and furan-functionalized Gel, and the pre- and post-gelation chemical structure of the resulting hydrogel precursors was fully investigated. Potential uses of the developed hydrogel in the pharmaceutical industry were also evaluated by looking at its gelation duration, temperature, morphologies, swelling, biodegradation, and mechanical characteristics. The Gel-FM hydrogels were safe, showed good antimicrobial activity, and had a low storage modulus, which meant that they could be used in many biochemical fields. The encapsulation and release of tramadol from the hydrogel system in phosphate-buffered saline (PBS) at 37 °C were investigated under acidic and slightly alkaline conditions, replicating the stomach and intestinal tracts, respectively. The in-vitro release profile showed promising results for drug encapsulation, revealing that the drug could safely be well-encapsulated in acidic stomach environments and released more quickly in slightly alkaline intestinal environments. This implies that the hydrogels produced could work well as polymers for specifically delivering medication to the colon.

Design, synthesis, docking, ADMET and anticancer evaluations of N-alkyl substituted iodoquinazoline derivatives as dual VEGFR-2 and EGFR inhibitors.

Fifteen new 1-alkyl-6-iodoquinazoline derivatives 5a-d to 9a-e were designed and synthesized and their anticancer activities were evaluated against HepG2, MCF-7, HCT116 and A549 cancer cell lines via dual targeting of EGFR and VEGFR-2. The newly synthesized compounds were designed based on the structure requirements of the target receptors and were confirmed using spectral data. Compound 9c showed the highest anticancer activities with EC50 = 5.00, 6.00, 5.17 and 5.25 µM against HepG2, MCF-7, HCT116 and A549 cell lines correspondingly. Moreover, compounds 5d, 8b, 9a, 9b, 9d, and 9e exhibited very good anticancer effects against the tested cancer cell lines. The highly effective seven derivatives 5d, 8b, 9a-e were examined against VERO normal cell lines to estimate their cytotoxic capabilities. Compounds 9c, 9b, 9d, 9a, 9e and 5d excellently inhibited VEGFR-2 activity with IC50 = 0.85, 0.90, 0.90, 1.00, 1.20 and 1.25 µM respectively. Moreover, compounds 9c, 9d, 9e, 5d, 8b and 9b excellently inhibited EGFRT790M activity with IC50 = 0.22, 0.26, 0.30, 0.40, 0.45 and 0.50 µM respectively. Also, compounds 9c, 9d and 9e excellently inhibited EGFRWT activity with IC50 = 0.15, 0.20 and 0.25 µM respectively. As planned, compound 9c showed excellent dual EGFR/VEGFR-2 inhibitory activities. Consonantly, ADMET study was calculated in silico for the supreme three worthwhile compounds 9b, 9c and 9e in contrast to sorafenib and erlotinib as reference drugs. The obtained results concluded that, our compounds might be useful as prototype for design, optimization, adaptation and investigation to have more powerful and selective dual VEGFR-2/EGFRT790M inhibitors with higher antitumor activity.

Synthesis, crystal structure, DFT, Hirshfeld surface analysis, energy frameworks and in-Silico drug-targeting PFKFB3 kinase of novel triazolequinoxalin derivative (TZQ) as a therapeutic Strategy against cancer.

Overall, drug design is a dynamic and evolving field, with researchers constantly working to improve their understanding of molecular interactions, develop new computational methods, and explore innovative techniques for creating effective and safe medications. The process can involve steps such as the identification of targets, the discovery of lead compounds, lead optimization, preliminary testing, human trials, regulatory approval and finally post-marketing surveillance, all aimed at bringing a new drug from concept to market. In this article, the synthesis of the novel triazolequinoxalin (TZQ) 1-((1-hexyl-1H-1,2,3-triazol-5-yl)methyl)-3-phenylquinoxalin-2(1H)-one (4) is reported. The structure has been identified with a variety of spectroscopic methods (1H, 13C NMR, and LC-MS) and finally, the structure has been determined by X-ray diffraction (XRD) studies. The TZQ molecule has crystallized in the monoclinic space C2/c group with unit cell dimensions a = 41.201(2) Å, b = 10.6339(6) Å, c = 9.4997(4) Å, ß = 93.904(4). The crystal structure is stabilized by intermolecular interactions (N-H ⋯ O and N-H … Cg) occurring within the molecule. The presence of these intermolecular interactions is evaluated through analysis of Hirshfeld surfaces (HS) and two-dimensional (2D) chemical fingerprints map. Additionally, energy frameworks were employed to identify the prevailing interaction energy influencing the molecular arrangement. Density Functional Theory (DFT) calculations were computed to establish concurrence between theoretical and experimental results. Furthermore, the HOMO-LUMO energy levels were determined using the B3LYP/6-31+G(d, p) level of theory. Finally, molecular docking was used to predict the anti-cancer activity of the compound (4) against PFKFB3 kinase and presented noticeable hydrophilic and hydrophobic interactions at the active site region.

Chiral resolution of (±)-flurbiprofen using molecularly imprinted hydrazidine-modified cellulose microparticles.

Flurbiprofen (FP) is one of the non-steroidal anti-inflammatory drugs (NSAIDs) commonly used to treat arthritic conditions. FP has two enantiomers: S-FP and R-FP. S-FP has potent anti-inflammatory effects, while R-FP has nearly no such effects. Herein, molecularly imprinted microparticles produced from hydrazidine-cellulose (CHD) biopolymer for the preferential uptake of S-FP and chiral resolution of (±)-FP were developed. First, cyanoethylcellulose (CECN) was synthesized, and the -CN units were transformed into hydrazidine groups. The developed CHD was subsequently shaped into microparticles and ionically interacted with the S-FP enantiomer. The particles were then imprinted after being cross-linked with glutaraldehyde, and then the S-FP was removed to provide the S-FP enantio-selective sorbent (S-FPCHD). After characterization, the optimal removal settings for the S- and R-FP enantiomers were determined. The results indicated a capacity of 125 mg/g under the optimum pH range of 5-7. Also, S-FPCHD displayed a noticeable affinity toward S-FP with a 12-fold increase compared to the R-FP enantiomer. The chiral resolution of the (±)-FP was successfully attempted using separation columns, and the outlet sample of the loading solution displayed an enantiomeric excess (ee) of 93 % related to the R-FP, while the eluent solution displayed an ee value of 95 % related to the S-FP.