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Background: Type 2 diabetes has become a significant global health challenge. Numerous drugs have been developed to treat the condition, either as standalone therapies or in combination when glycemic control cannot be achieved with a single medication. As existing treatments often come with limitations, there is an increasing focus on creating novel therapeutic agents that offer greater efficacy and fewer side effects to better address this widespread issue. Methods: The methylene derivatives 3a,b were coupled with phenyl/ethyl isothiocyanate in the basic medium, and dimethyl sulfate was subsequently added. Further, 5a–d were reacted with the quinoline/naphthalene hydrazides 6a,b. The target compounds 7a–g were subjected to the in vitro enzyme inhibition studies on α-glucosidase, α-amylase, and aldose reductase. Results: 7g exerted remarkable inhibitory effects on α-glycosidase [Inhibitory Concentration (IC50): 20.23 ± 1.10 µg/mL] and α-amylase (17.15 ± 0.30 µg/mL), outperforming acarbose (28.12 ± 0.20 µg/mL for α-glycosidase and 25.42 ± 0.10 µg/mL for α-amylase), and exhibited a strong inhibition action on aldose reductase (12.15 ± 0.24 µg/mL), surpassing quercetin (15.45 ± 0.32 µg/mL) and the other tested compounds. In a computational study, 7g demonstrated promising binding affinities (−8.80, −8.91 kcal/mol) with α-glycosidase and α-amylase, compared to acarbose (−10.87, −10.38 kcal/mol) for α-glycosidase and α-amylase. Additionally, 7g had strong binding with aldose reductase (−9.20 kcal/mol) in comparison to quercetin (−9.95 kcal/mol). Molecular dynamics (MDs) simulations demonstrated that 7g remained stable over a 100 ns simulation period, and the binding free energy estimates remained consistent throughout this time. Conclusions: We reported the modification of quinoline and naphthalene rings to hydrazineylidene–propenamides 7a–g using various synthetic approaches. 7g emerged as a leading candidate, exhibiting greater inhibition of α-glycosidase, α-amylase, and aldose reductase. These findings underscore their potential as essential molecules for the development of innovative antidiabetic treatments. [ABSTRACT FROM AUTHOR]

In this work, we discuss the development of a long‐lasting enantioselective material for the effective enantio‐recognition of S‐3,4‐methylenedioxymethamphetamine (S‐MDMA) and chiral separation of the (±)‐MDMA racemate using a crosslinked poly(acrylic acid‐4‐vinylpyridine) copolymer. The first step was the synthesis and characterization of an acryloyl‐S‐MDMA amide. After that, the free radical initiator azobisisobutyronitrile was used to copolymerize the synthesized chiral amide with 4‐vinylpyridine and divinylbenzene. The incorporated S‐MDMA species were extracted from the polymeric particles by heating them with sodium hydroxide, followed by rinsing with hydrochloric acid. This developed the molecularly imprinted S‐MDMA particles, which were visualized with a scanning electron microscope and Fourier transform infrared spectroscopy. The selectivity parameters indicated a higher affinity of the fabricated S‐MDMA imprinted particles toward S‐MDMA, around 10‐fold higher than that related to R‐MDMA. Results from Langmuir adsorption experiments at pH 6 demonstrated a maximal capacity of 142 mg g−1. In addition, the values of enantiomeric excess were found to be 94.5% and 79.4% for R‐ and S‐MDMA in the loading and eluant solutions, respectively, after optical separation was done using the column technique. © 2023 Society of Industrial Chemistry. [ABSTRACT FROM AUTHOR]

Impregnation of phosphine‐decorated polymer‐immobilized ionic liquid with the tetrachloroaurate anion results in reduction of the gold(III) to gold(I) with concomitant oxidation of the phosphine to its oxide. In situ reduction of the resulting precursor, AuCl@O = PPh2‐PEGPIILS, generated the corresponding O = PPh2‐PEGPIIL‐stabilized AuNPs, AuNP@O = PPh2‐PEGPIILS, which is a highly active and selective catalyst for the solvent‐dependent partial reduction of nitrobenzene to N‐phenylhydroxylamine in water and azoxybenzene in ethanol. The initial TOFs are comparable to those obtained with gold nanoparticles generated by reduction of tetrachloroaurate‐impregnated phosphine oxide‐decorated polymer‐immobilized ionic liquid AuCl4@O = PPh2‐PEGPIILS, i.e., the activity and selectivity profiles do not appear to depend on whether the AuNPs are generated from Au(III) or in situ‐generated Au(I). In stark contrast, gold nanoparticles prepared by NaBH4 reduction of AuCl@PPh2‐PEGPIILS based on gold(I) confined in phosphine‐modified polymer‐immobilized ionic liquid gave markedly lower initial TOFs. The use of dimethylamine borane (DMAB) as the hydrogen donor resulted in a substantial and dramatic enhancement in activity for reductions conducted in water compared with NaBH4 and the initial TOF of 20,400 mol nitrobenzene converted mol Au−1 h−1 obtained with AuNPs generated in situ from AuCl4@O = PPh2‐PEGPIILS is among the highest to be reported for the metal nanoparticle catalyzed selective reduction of nitrobenzene to N‐phenylhydroxylamine; this is a significant improvement on existing protocols, which should enable the partial selective reduction of nitroarenes to be conducted in water with a low catalyst loading under extremely mild conditions. [ABSTRACT FROM AUTHOR]

Novel inhibitors of epidermal growth factor receptor (EGFR) T790M /vascular endothelial growth factor receptor-2 (VEGFR-2) were synthesized based on the iodoquinazoline scaffold linked to different heteroaromatic, aromatic, and/or aliphatic moieties. The novel derivatives were in vitro examined for anticancer activities against A549, HCT116, michigan cancer foundation-7 (MCF-7), and HepG2 cells. Molecular modeling was applied to discover their orientation of binding with both VEGFR-2 and EGFR active sites. Compounds 8d, 8c, 6d, and 6c indicated the highest cytotoxicity with IC 50  = 6.00, 6.90, 6.12 and 6.24 µM, 7.05, 7.35, 6.80, and 6.80 µM, 5.75, 7.50, 6.90, and 6.95 µM, and 6.55, 7.88, 7.44, and 7.10 µM against the A549, HepG2, HCT116, and MCF-7 cell lines, correspondingly. The cytotoxicity against normal VERO (normal african green monkey kidney cells) of the extremely active eight compounds 6a-d and 8a-d was evaluated. Our compounds exhibited low toxicity concerning normal VERO cells with IC 50  = 45.66-51.83 μM. Furthermore, inhibition assays for both the EGFR T790M and VEGFR-2 enzymes were done for all compounds. Remarkable inhibition of EGFR T790M activity was achieved with compounds 6d, 8d, 6c, and 8c at IC 50  = 0.35, 0.42, 0.48, and 0.50 µM correspondingly. Moreover, remarkable inhibition of VEGFR-2 activity was achieved with compounds 8d, 8c, 6d, and 6c at IC 50  = 0.92, 0.95, 1.00, and 1.20 µM correspondingly. As planned, derivatives 6d, 8d, 6c, and 8c presented exceptional inhibition of both EGFR T790M /VEGFR-2 activities. Finally, in silico absorption, distribution, metabolism, excretion and toxicity (ADMET) studies were made for the highly active four compounds 6c, 6d, 8c, and 8d in comparison with erlotinib and sorafenib as reference standards., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

Fifteen new iodoquinazoline derivatives, 5a,b to 18, are reported in this study and their anticancer evaluation as dual inhibitors of EGFR WT and EGFR T790M . 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 IC 50 = 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 IC 50 increasing from 43.44 to 52.11 μM. All compounds were additionally assessed for their EGFR WT and EGFR T790M inhibitory activities. Additionally, their ability to bind with EGFR WT 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 IC 50 ranging from 0.17 to 0.50 μM. Moreover, compounds 18, 17, 14b and 16 remarkably inhibited EGFR T790M activity with IC 50 = 0.25, 0.30, 0.36 and 0.40 μM respectively. As planned, compounds 18, 17 and 14b showed excellent dual EGFR WT /EGFR T790M inhibitory activities. Finally, our compounds 18, 17 and 14b displayed good in silico ADMET calculated profiles., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)