Derivatives 2a-c Research Articles

Synthesis, DFT investigation, molecular docking analysis, ADMET studies, and biological evaluation of a novel series of imidazolidinone derivatives as potential antimicrobial agents

In this study, we constructed twenty novel imidazolidinone derivatives via the reaction of 2-(methylthio)-3,5-dihydro-4H-imidazol-4-one derivatives (1a-c) with some active methylene reagents and nitrogen nucleophiles. The synthesized compounds were confirmed through spectral analysis such as 1H NMR, 13C NMR, FT-IR, and MS. Moreover, the synthesized compounds were optimized and utilizing the DFT/B3LYP/6-31(G) basis set to investigate their energies and the presence of two forms of isomers (E and Z). The results confirmed the stability of the E form. ADMET of new imidazolidinones was also studied to investigate their lipophilicity and Lipinski's rule for determination of their physiological biological analysis. Also, the antimicrobial activity of new compounds on Escherichia coli, Klebsiella pneumonia, Staphylococcus aureus, Streptococcus mutans, Candida albicans, and Aspergillus Nigar using the inhibition zone technique were evaluated. The results demonstrate that compound 11c showed higher activity rather than other compounds due to the presence of piperazine moiety out of the plane of the benzene ring. Additionally, the docking study showed an electrostatic bonding interaction of the hydrogen of 11c and the amino acids of two proteins such as PDBID: 3t88 and 2wje.

Rational design, synthesis, computational studies and biological evaluation of new diazepanone derivatives: Crystal structure of 2,7-bis(4-chlorophenyl)-1,3-dimethyl-1,4-diazepan-5-one

Structural and biological evaluation of newly designed and synthesized diazepanone derivatives (3a-c) with modified functionalities is reported in this paper, as liponucleoside class of antibiotics possessing 1,4-diazepanone as core moiety are under investigation since last decade to improvise their drug action. FT-IR, HR-ESI-MS, 1H NMR and 13C NMR spectral studies are used for the structural characterization of synthesized compounds (3a-c). 1H NMR spectral data reveal that the diazepanone ring exhibits chair conformation in solution state. The solid state geometry for compound 3a acquired by SC-XRD study also in favour of chair conformation of the diazepanone ring with equatorial orientation of all the substituents. Comparison of experimental bond parameters with theoretical results attained by DFT studies using B3LYP/6–311G++ (d,p) basis set are in good agreement. Molecular electrostatic potential surface (MEPS) and HOMO-LUMO energies are used to elucidate the topology and physicochemical parameters of 3a. Nature of crystal packing is ascertained by Hirshfeld surface and its delineated 2D-Fingerprint plot in addition with the SC-XRD evidences. Antibacterial evaluation of (3a-c) against tested bacterial strains reveals that the compounds have remarkable antibacterial potencies compared to tested standard drug. Among the compounds 3a-c, the compound 3c with fluoro-substitution on the phenyl ring shows highest activity.

Unveiling the anti-cancer potentiality of phthalimide-based Analogues targeting tubulin polymerization in MCF-7 cancerous Cells: Rational design, chemical Synthesis, and Biological-coupled Computational investigation

The present study deals with an anti-cancer investigation of an array of phthalimide-1,2,3-triazole molecular conjugates with various sulfonamide fragments against human breast MCF-7 and prostate PC3 cancer cell lines. The targeted 1,2,3-triazole derivatives 4a-l and 6a-c were synthesized from focused phthalimide-based alkyne precursors using a facile click synthesis approach and were thoroughly characterized using several spectroscopic techniques (IR, 1H, 13C NMR, and elemental analysis). The hybrid click adducts 4b, 4 h, and 6c displayed cytotoxic potency (IC50 values of 1.49, 1.07, and 0.56 μM, respectively) against MCF-7 cells. On the contrary, none of the synthesized compounds showed apparent cytotoxic efficacy for PC3 cells (IC50 ranging from 9.87- >100 μM). As a part of the mechanism analysis, compound 6c demonstrated a potent inhibitory effect (78.3 % inhibition) of tubulin polymerization in vitro with an IC50 value of 6.53 µM. In addition, biological assays showed that compound 6c could prompt apoptotic cell death and induce G2/M cell cycle arrest in MCF-7 cells. Accordingly, compound 6c can be further developed as an anti-breast cancer agent through apoptosis-induction.

Some New Bis-(1,2,4-Triazole) Compounds: Synthesis, Characterization and Urease Enzyme Inhibition

In this study, thiosemicarbazide derivatives (2a-c) were obtained from the reaction of acetohydrazide derivative 1,2,4-triazole compound (1) with methyl isothiocyanate, phenyl isothiocyanate, and 4-methylphenyl isothiocyanate compounds, respectively. Then, by intramolecular cyclization of 2a-c compounds, bis-(1,2,4-triazole) compounds (3a-c) were synthesized. The synthesized compounds' chemical structures were verified using FT-IR, 1H-NMR, and 13C-NMR spectroscopic methods. In addition, the urease enzyme inhibition of the synthesized compounds was evaluated using the Weatherburn method in vitro. All newly synthesized compounds showed urease enzyme inhibition in the range of 15.00 ± 0.10 to 16.00 ± 0.25 IC50 (µg/mL) compared to standard thiourea (IC50 = 15.75 ± 0.15 µg/mL).

Synthesis and antioxidant properties of novel hybrid molecules containing gallic acid and thiazolidinone moieties

Thiazolidinones, are characterized by a thiazolidine ring structure, have highly biological applications. So, novel hybrid thiazolidinone moieties containing gallic acid were synthesized via cyclo-condensation process or standard Knoevenagel reactions. Hydrazineyl-thiazol-4(5H)-one 2 derivative was synthesized to condensed with benzaldehydes to afford benzylidene thiazolidinone derivatives 3a-c. Also, the product 2 reacted with benzyl bromide or nitro benzyl bromide to give their corresponding methylene active derivatives 4a,b which were readily reacted with aromatic aldehydes to produce 5-arylidene derivatives 5a-f via Knoevenagel reactions. The new thiazolidine derivatives were elucidated according to their spectroscopic and elemental analyses. Two thiazolidinone derivatives 4a,b were elucidated via X-ray analysis. Also, antioxidant activity of the new products were run by DPPH assay and in comparison with reference antioxidants (ascorbic acid and BHT). The results revealed that eight compounds was higher than BHT and was increasing in the following order 4a < 5f < 5a< 3c < 5b < 5d < 3a< 5c. The antioxidant activity of ascorbic acid was higher than all compounds in which compound 5c was very close in its activity with the ascorbic acid.

Benzyloxychalcone Hybrids as Prospective Acetylcholinesterase Inhibitors against Alzheimer's Disease: Rational Design, Synthesis, In Silico ADMET Prediction, QSAR, Molecular Docking, DFT, and Molecular Dynamic Simulation Studies.

Acetylcholinesterase inhibitors (AChEIs) are crucial therapeutic targets for both the early and severe stages of Alzheimer's disease (AD). Chalcones and their chromone-based derivatives are well-known building blocks with anti-Alzheimer properties. This study synthesized 4-benzyloxychalcone derivatives and characterized their structures using IR, 1H NMR, 13C NMR, and HRMS. Additionally, the synthesized 4-benzyloxychalcone derivatives were tested for anti-acetylcholinesterase (AChE) activity. The synthesized compounds outperformed galantamine, which is used as a positive control against acetylcholinesterase. Utilizing an acetylcholinesterase (AChE) receptor (PDB ID: 4EY7)-chalcone derivative (12a-c), a molecular docking investigation was performed on the synthesized compounds. The goal was to predict the binding sites and energies of the derivatives with respect to the receptor amino acids. The dynamic behavior of the ligand-receptor complex resulting from the interaction of the best docking compounds 12a and 12c with the acetylcholinesterase receptor was used to analyze the stability via MD simulation. MM/GBSA and MM/PBSA were used to calculate free binding energies using snapshots from system trajectories. Advanced computational approaches incorporating long-range corrections were utilized to calculate the molecular characteristics of chalcone derivatives 12a-c at the DFT/wB97XD/6-311++G(d,p) level. We used the molecular electrostatic surface potential (MESP) with high-quality data and visualization to find the most active site in these molecules. Reactivity descriptors, including the condensed Fukui function, chemical hardness (η), dual descriptors, chemical potential (μ), and electrophilicity (ω), were calculated for the chalcone derivatives.

Synthesis, characterization, and MAO inhibitory activities of three new drug-like N-acylhydrazone derivatives

In this study, three new N-acylhydrazone derivatives with the structural motif of N'-(substitutedbenzylidene)-3-(5-methyl-2-benzoxazolinon-3-yl)propanehydrazide (5a-c) are prepared and evaluated for their MAO inhibitory activities. The structures of the synthesized compounds are elucidated through spectral methods (IR, 1H-NMR, 13C-NMR), elemental analysis and single crystal X-ray crystallography. Detailed structural and Hirshfeld surface analyses of compounds (5a-c) have provided further insights into their molecular and crystal structures and also their intermolecular interactions. Complementing the spectral and structural analyses confirmed the E-configurations of the compounds in the solid state. The Hirshfeld surface analyses of the crystal structures have indicated that the most important contributions for the crystal packings are from H ... H, H … C/C … H and H … O/O … H (for 5a-c) and H … F/F … H (for 5b and c). In vitro tests are revealed their MAO inhibitory activities, surpassing reference compounds moclobemide and selegiline. Notably, synthesized N-acylhydrazone derivatives (5a-c) are exhibited superior MAO inhibitory activities, with a higher selectivity for MAOB over MAOA (SI >10). Molecular docking studies are provided insights into the binding modes of the compounds in the active site of the target enzyme. Theoretical ADME (Absorption, Distribution, Metabolism and Excretion), gastrointestinal absorption and blood-brain barrier permeation studies revealed that the compounds possess pharmacological attributes resembling those of typical drugs. This properties and MAO inhibitory activities of N-acyl hydrazone derivatives emphasize their potentials as promising candidates in the field of medicinal chemistry.

Synthesis, DFT, and in silico biological evaluation of chalcone bearing pyrazoline ring against Helicobacter pylori receptors

Peptic ulcer disease (PUD), often caused by Helicobacter pylori infection, is a prevalent gastrointestinal condition characterized by the erosion of the gastric or duodenal mucosal lining. H. pylori adheres to gastric epithelial cells, secreting toxins and disrupting the stomach's defenses. H. pylori relies on various receptors to establish infection, making these molecules attractive therapeutic targets. This study aimed to develop novel anti-ulcer compounds by combining benzothiazole, pyrazoline, and chalcone pharmacophores. A series of chalcone derivatives 4a-c were synthesized via Claisen-Schmidt condensation and characterized using spectroscopic techniques such as FT-IR, NMR and elemental analysis. The DFT calculations, using B3LYP method with 6-311G basis set, revealed the p-tolyl derivative 4b exhibited the highest thermal stability while the p-bromophenyl derivative 4c showed the lowest stability but highest chemical reactivity. The HOMO-LUMO energy gaps as well as the dipole moments decreased in the order: 4b > 4a >4c, reflecting a similar reactivity trend. Molecular docking showed ligands 4a-c bound effectively to the H. pylori urease enzyme, with docking scores from −5.3862 to −5.7367 kcal/mol with superior affinity over lansoprazole. Key interactions involved hydrogen bonds and hydrophobic pi-hydrogen bonds with distances ranging 3.46–4.34 Å with active site residues ASN666, SER714 and ASN810. The combined anti-inflammatory, antimicrobial, and H. pylori anti-adhesion properties make these novel chalcones promising PUD therapeutic candidates.

Synthesis of Some Novel Thiophene Analogues as Potential Anticancer Agents.

The aim of this study involves the synthesis novel thiophene analogues that can be used as anticancer medications through a strategic multicomponent reaction connecting ethyl 4-chloroacetoacetate (1), phenyl isothiocyanate, and a series of active methylene reagents, including ethyl acetoacetate (2), malononitrile, ethyl cyanoacetate, cyanoacetamide 6a-c, N-phenyl cyanoacetamide derivatives 13a-c, and acetoacetanilide derivatives 18. This reaction was facilitated by dry dimethylformamide with a catalytic quantity of K2CO3. The resultant thiophene derivatives were identified as 4, 8a-b, 9, 12a-d, 15a-c, and 20a-b. Further reaction of compound 4 with hydrazine hydrate yielded derivative 5, respectively. When compound 1 was refluxed with ethyl 3-mercapto-3-(phenylamino)-2-(p-substituted phenyldiazenyl)acrylate 10a-e in the presence of sodium ethoxide, it produced thiophene derivatives 12a-d. Comprehensive structural elucidation of these newly synthesized thiophene-analogues was accomplished via elemental and spectral analysis data. Furthermore, the study delves into the cytotoxicity of the newly synthesized thiophenes was evaluated using the HepG2, A2780, and A2780CP cell lines. The amino-thiophene derivative 15b exhibited an increased growth inhibition of A2780, and A2780CP with IC50 values 12±0.17, and 10±0.15 μM, respectively compared to Sorafenib with IC50 values 7.5±0.54 and 9.4±0.14. This research opens new avenues for developing thiophene-based anticancer agents.

Exploring of novel oxazolones and imidazolones as anti-inflammatory and analgesic candidates with cyclooxygenase inhibitory action.

Aim: Over the last fewdecades, therapeutic needs have led to a search for safer COX-2 inhibitors with potential anti-inflammatory and analgesic activity. Materials & methods: A new series of oxazolone and imidazolone derivatives 3a-c and 4a-r were synthesized and evaluated as anti-inflammatory and analgesic agents. COX-1/COX-2 isozyme selectivity testing and molecular docking were performed. Results: All compounds showed good activities comparable to those of the reference, celecoxib. The most active compounds 3a, 4a, 4c, 4e and 4f showed promising gastric tolerability with an ulcer index lower than that of celecoxib. The molecular docking of p-methoxyphenyl derivative 4c showed alkyl interaction with the side pocket His75 of COX-2 and achieved the best anti-inflammatory activity, with a COX-2 selectivity index better than that of celecoxib.

Triazole-bearing sulfonamide linkage: Synthesis, characterization, and investigation as a versatile corrosion inhibitor

Novel focused three 1,4-disubstituted-1,2,3-triazoles 5a-c labeled ISMs (ISM-H, ISM-F & ISM-N) and tethering sulfonamide moieties were designed and synthesized by the 1,3-dipolar cycloaddition of some appropriate aromatic O-alkyne derivatives 3a-c and 4-azido-N-carbamimidoylbenzenesulfonamide 4 as an efficient and common approach in click chemistry. The structures of the resulted click products were elucidated based on their spectral data. The newer synthesized triazoles were well investigated as corrosion inhibitors for carbon steel and Al alloy in HCl solution utilizing electrochemical, weight loss, surface research, and density functional theory (DFT) techniques. The electrochemical impedance spectroscopy (EIS) results revealed that a low inhibitor dosage of compounds ISM-H and ISM-F exhibited potential corrosion inhibition. The ISM-N and ISM-H derivatives exhibited a chemisorption nature and showed the potential inhibition at 60 °C. The surface studies: scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX) and Fourier Transform Infrared Spectroscopy (FTIR) reveals the formation inhibitor film above the metal surface.

Synthesis, Antiproliferative Evaluation, and Molecular Docking of Thieno[3,2-e]indazole Derivatives

Background: Although indazole derivatives are rare and may not be available easily in nature, there are many reports demonstrating their pharmaceutical and other applications. Objective: This study aimed to synthesize new indazole derivatives and evaluate their antiproliferative activity to produce new anti-cancer agents. Method: The 2-aryllidenecyclohexane-1,3-dione derivatives 3a-c were obtained through the reaction of cyclohexane-1,3-dione with aromatic aldehydes used for the synthesis of thieno-[3,2-e]indazole derivatives. These derivatives were characterized by extensive analytical and spectral studies and were further used as starting materials for some heterocyclic transformations to produce biologically active compounds. The antiproliferative activities of the newly synthesized compounds were evaluated against the six cancer cell lines, A549, HT-29, MKN-45, U87MG, SMMC-7721, and H460. Most of the tested compounds exhibited high cytotoxicity except a few compounds. Results: In this study, new compounds were synthesized, characterized, and evaluated toward the selected six cancer cell lines. All tested compounds displayed potent c-Met enzymatic activity with IC50 values ranging from 0.25 to 10.30 nM and potent prostate PC-3 cell line inhibition with IC50 values ranging from 0.17 to 9.31mM. Conclusion: The results obtained in this work demonstrated that the variations in substituents within the aryl moiety, together with the attached heterocyclic ring, have a notable influence on the antiproliferative activity. The results obtained in this work encourage further work in the future.

Synthesis, Characterization, Molecular Docking Studies and Biological Evaluation of Thiazole Schiff Base Analogs

In this work, potentially safe few Schiff base compounds containing a thiazole moiety were synthesized and characterized. Three thiazole derivatives (2a-c) were successfully synthesized through a two-step reaction involving substituted benzaldehyde, thiosemicarbazide and 1,3-dichloroacetone. The elucidation of the synthesized compounds was accomplished by using spectral studies. Antimicrobial activities demonstrated that some compounds exhibited moderate effectiveness against microbes, compared to the standard antibiotic’s ceftriaxone and amphotericin B, using the disc diffusion technique. In the DPPH free radical scavenging assay, all compounds displayed promising antioxidant effectiveness. Moreover, the molecular docking studies showed that thiazole Schiff base analogs effectively bind to potential receptor binding sites.

تخليق(توليف) مشتقات الثيوسيمياكاربازيد الالدهيدية في وسط كحولي

Thiosemicarbazide derivatives (3a-c) were synthesized by reacting Thiosemicarbazide with aromatic aldehydes in an alcoholic medium. The reaction was monitored by TLC, and the structural composition of the derivatives was confirmed by melting point, IR, and ¹HNMR spectroscopy. Thiosemicarbazide derivatives are important in the biological field and can form complexes with some transition elements. Keywords:Thiosemicarbazide , Aldehehydes, Synthesis, Derivatives.

Synthesis, characterization, and computational study of novel carvacrol-based 2-aminothiol and sulfonic acid derivatives as metabolic enzyme inhibitors

Eight new 2-aminothiols (69–96%) and three new sulfonic acids (51–76%) were synthesized and characterized by NMR and HRMS spectra. This study presents the inhibitory effects of a series of novel carvacrol-based 2-aminothiol and sulfonic acid derivatives (3a-f,4a-c) against human carbonic anhydrase I and II isozymes (hCA I and II) acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and α-glycosidase. Ki values were calculated as 12.52±3.61–335.65±60.56 nM for hCA I, 12.20±3.59–389.69±119.41 nM for hCA II, 1.79±0.56–84.86±23.34 nM for AChE, 6.57±2.54–88.05±21.05 nM for BChE and 14.63±4.76–116.39±33.70 nM α-glucosidase enzymes. Also, the inhibition effects of novel carvacrol-based 2-aminothiol (3a-h) and sulfonic acid derivatives (4a-c) were compared to standard and clinically used inhibitors of acetazolamide, Tacrine and acarbose, respectively. Molecular modeling studies of novel compounds, docking scores, and free binding energies were calculated. The activity results of the compounds were found to be compatible with the docking scores. Molecular dynamics studies were conducted with the best activity against CA I and CA II compounds, 4b (IC50: 4.76 nM) and 4a (IC50: 4.36 nM), respectively. In Dynamic Simulation studies, it was observed that the compounds remained stable at the active sites of the proteins.

Orthopalladated imidazolones and thiazolones: synthesis, photophysical properties and photochemical reactivity.

The reaction of Pd(OAc)2 with (Z)-5-arylidene-4-(4H)-imidazolones (2a-e) and (Z)-4-arylidene-5(4H)-thiazolones (3a-e) in trifluoroacetic acid results in the corresponding orthopalladated dinuclear complexes (4a-e, imidazolones; 11a-d, thiazolones) with trifluoroacetate bridges through regioselective C-H activation at the ortho position of the 4-arylidene group. Compound 4e, which contains an imidazolone substituted at 2- and 4-positions of the arylidene ring with methoxide groups and exhibits strong push-pull charge transfer, is an excellent precursor for the synthesis of fluorescent complexes with green yellowish emission and remarkable quantum yields. Breaking the bridging system with pyridine yields the mononuclear complex 5e (ΦF = 5%), while metathesis of trifluoroacetate ligands with chloride leads to the dinuclear complex 6e, also a precursor of fluorescent complexes by breaking the chloride bridging system with pyridine (7e, ΦF = 7%), or by substitution of chloride ligands with pyridine (8e, ΦF = 15%) or acetylacetonate (9e, ΦF = 2%). In addition to notable photophysical properties, dinuclear complexes 4 and 11 also exhibit significant photochemical reactivity. Thus, irradiation of orthopalladates 4a-c and 11a-c in CH2Cl2 with blue light (465 nm) proceeds via [2 + 2] photocycloaddition of the CC double bonds of imidazolone and thiazolone ligands, yielding the corresponding cyclobutane-bridging diaminotruxillic derivatives 10a-c and 12a-c, respectively.

Iodoquinazoline-derived VEGFR-2 and EGFRT790M dual inhibitors: Design, synthesis, molecular docking and anticancer evaluations

Herein, we report the synthesis of a series of new fourteen iodoquinazoline derivatives 7a-c to 13a-e and their evaluation as potential anticancer agents via dual targeting of EGFRT790M and VEGFR-2. The new derivatives were designed according to the target receptors structural requirements. The compounds were evaluated for their cytotoxicity against HepG2, MCF-7, HCT116 and A549 cancer cell lines using MTT assay. Compound 13e showed the highest anticancer activities with IC50 = 5.70, 7.15, 5.76 and 6.50 µM against HepG2, MCF-7, HCT116 and A549 cell lines correspondingly. Compounds 7c, 9b and 13a-d exhibited very good anticancer effects against the tested cancer cell lines. The highly effective six derivatives 7c, 10, 13b, 13c, 13d and 13e were examined against VERO normal cell lines to estimate their cytotoxic capabilities. Our conclusion revealed that compounds 7c, 10, 13b, 13c, 13d and 13e possessed low toxicity against VERO normal cells with IC50 prolonging from 41.66 to 53.99 μM. Also compounds 7a-c to 13a-e were further evaluated for their inhibitory activity against EGFRT790M and VEGFR-2. Also, their ability to bind with both EGFR and VEGFR-2 receptors was examined by molecular modeling. Compounds 13e, 13d, 7c and 13c excellently inhibited VEGFR-2 activity with IC50 = 0.90, 1.00, 1.25 and 1.50 µM respectively. Moreover, Compounds 13e, 7c, 10 and 13d excellently inhibited EGFRT790M activity with IC50 = 0.30, 0.35, 0.45 and 0.47 µM respectively. Finally, our derivatives 7b, 13d and 13e showed good in silico calculated ADMET profile.

Synthesis, Thermal, DFT Calculations, HOMO-LUMO, MEP, and Molecular Docking Analysis of New Derivatives of Imidazolin-4-Ones

This work focuses on synthesizing new imidazolin-4-one derivatives (2a-c), akin to leucettamine B analogs, via microwave-assisted transamination reactions. This reaction was carried out between 3-alkyl-5-dimethylamino-2-thioxo-imidazolidin-4-one (1a-c) and aniline. The structural integrity of the synthesized compounds was confirmed using NMR and MS spectroscopy, and their configurations were validated through DFT calculations. Analyses encompassed molecular electrostatic potential, frontier molecular orbitals, HOMO-LUMO energies, energy band gap, and global chemical reactivity descriptors, providing comprehensive insights into their characteristics. The investigation extended to the biological domain, employing substance activity spectra prediction (PASS) and molecular docking with Autodock Vina4 program. Notably, this holistic assessment aimed to gauge the potential regulatory effect of the compounds on cholesterol. This integrated approach contributes to compound design understanding and potential applications, spanning drug design and broader biomedical contexts.

Design, synthesis and anti-hyperglycemic assessments of novel 5-benzylidenethiazolidine-2,4-dione derivatives as PPAR-γ agonist

The treatment of diabetes mellitus still relies predominantly on peroxisome proliferator-activated receptor-γ (PPAR-γ) therapy, known for its effectiveness. In this present study, a novel series of benzylidene-linked thiazolidine-2,4-dione compounds was conceptualized, synthesized, and subjected to assessment for their potential antidiabetic properties. Notably, among the compounds examined, 5-((Z)-4-(((E)-Propylidene)amino)benzylidene)thiazolidine-2,4-dione, designated as 4c, emerged as the most promising candidate, exhibiting the highest PPAR-γ agonistic activity with an EC50 value of 0.35 ± 0.52 μM. Additionally, molecular docking investigations were conducted on twelve 2,4-thiazolidinedione compounds, with a pyrazole moiety incorporated, within the ligand binding domain of PPAR-γ. Compound 4c, in particular, demonstrated a Glide XP score of −9.104, surpassing the score of the crystal ligand (Glide XP score = −7.482). Notably, both exhibited similar interactions with key amino acids, including HIE323, SER289, and GLN286. Furthermore, three derivatives (4a-c) with promising PPAR-γ agonistic activity and favorable molecular docking scores underwent in vivo evaluation for their capacity to lower blood glucose levels using a streptozotocin-induced diabetic mice model. In comparison to the reference drug pioglitazone, Compound 4c displayed commendable in-vivo performance across multiple parameters, encompassing serum HDL, serum LDL, serum total cholesterol, and serum triglyceride levels. Molecular dynamics simulations provided insights into the impact of ligand 4c, indicating its role in enhancing protein stability and rigidity. These findings emphasize its potential as a potent protein inhibitor, thus opening novel avenues for the intelligent design of molecules with high efficacy in the management of hyperglycemia.

Iodine and Nickel Ions Adsorption by Conjugated Copolymers Bearing Repeating Units of Dicyclopentapyrenyl and Various Thiophene Derivatives.

The synthesis of three conjugated copolymers TPP1-3 was carried out using a palladium-catalyzed [3+2] cycloaddition polymerization of 1,6-dibromopyrene with various dialkynyl thiophene derivatives 3a-c. The target copolymers were obtained in excellent yields and high purity, as confirmed by instrumental analyses. TPP1-3 were found to divulge a conspicuous iodine adsorption capacity up to 3900 mg g-1, whereas the adsorption mechanism studies revealed a pseudo-second-order kinetic model. Furthermore, recyclability tests of TPP3, the copolymer which revealed the maximum iodine uptake, disclosed its efficient regeneration even after numerous adsorption-desorption cycles. Interestingly, the target copolymers proved promising nickel ions capture efficiencies from water with a maximum equilibrium adsorption capacity (qe) of 48.5 mg g-1.