ABSTRACT A renewable task‐specific acidic ionic liquid, N ‐methyl‐2‐pyrrolidonium dihydrogen phosphate ([NMP]H 2 PO 4 ), was employed as a recyclable catalyst for the ultrasonication‐assisted, one‐pot, four‐component synthesis of novel quinoxaline–thiazole and quinoxaline–1,3,4‐thiadiazine hybrids. The methodology integrates ninhydrin, o ‐phenylenediamine, thiosemicarbazide/thiocarbohydrazide, and α ‐bromoacetophenone derivatives under solvent‐free conditions, delivering the target products in high yields and short reaction times. Reaction parameters, including catalyst loading, ultrasonic frequency, and bath temperature, were systematically optimized, with 15 mol% [NMP]H 2 PO 4 at 75°C and 50 kHz affording optimal conversions. The catalyst was readily recovered and reused over four cycles with minimal loss in activity. In‐silico ADMET and TOPKAT analyses revealed that most compounds complied with Veber's rule and exhibited acceptable drug‐likeness profiles, with the quinoxaline–1,3,4‐thiadiazine series showing comparatively lower predicted toxicity than their thiazole counterparts. This green synthetic approach offers an efficient and sustainable route to multifunctional heterocyclic scaffolds with promising pharmacological potential.

A new series of thiazolidine-2,4-dione tethered pyrazolyl coumarin hybrids (5a-i) was designed and synthesized. The synthetic strategy proved efficient and versatile, affording the desired hybrids in good to excellent yields. Characterization of the synthesized compounds was confirmed by spectral data (FTIR, H-1 NMR, C-13 NMR, and HRMS). The target compounds were further studied by in silico ADMET, TOPKAT toxicity, and preliminary PAINS assessment methods to evaluate their developability. Although the compounds occupy the beyond Rule-of-Five (bRo5) chemical space, most derivatives satisfied Veber's criteria, suggesting acceptable molecular flexibility and polar surface characteristics. Overall, this study establishes the TZD-pyrazole-coumarin hybrids as structurally promising multifunctional lead scaffolds and provides a rational platform for the design of second-generation analogues with improved pharmacokinetic properties.

A series of novel hybrids of 4,6-diphenyl pyrimidinone/pyrimidine-triazole were designed, synthesized, and systematically evaluated for their anticancer potential. The proposed compounds were efficiently synthesized via O-and N-propargylation of 4,6-diphenylpyrimidin-2(1H)-one followed by azide-alkyne cycloaddition catalysed by Cu(I) (click chemistry) to form two distinct classes of triazole-linked hybrids (9a-9j). All the synthesized compounds were characterized using IR, 1H/13C-NMR, and HRMS spectra. The antiproliferative activity of the compounds (9a-9j) was evaluated against human breast (MCF-7) and lung (A549) cancer cell lines, along with safety evaluation on human fibroblast cells (NIH). Several derivatives showed moderate to good antiproliferative activity with negligible toxicity towards normal cells. Particularly, compounds 9g and 9i showed promising cytotoxicity in MCF-7 and A549 cell lines, respectively. To rationalize the in vitro experimental results at the molecular level, molecular docking studies were performed against p38a Mitogen Activated Kinase (PDB: 4FA2), and found that compounds 9a and 9d exhibited higher docking scores compared to the co-crystallized ligand. Later, the 100 ns molecular dynamics simulations using the Desmond package confirmed the stability of complexes of the 4FA2 with 9a and 9d, supported by consistent hydrogen bonding, hydrophobic contacts, and stable RMSD and RMSF profiles throughout the run time. Overall, the integrated synthetic, biological, and computational examination highlights the hybrids of pyrimidinone/pyrimidine-triazoles as structurally robust scaffolds with promising antiproliferative activity and proposes the valuable structure-activity insights for further lead optimization.

A novel class of substituted 1,3,4‐oxadiazole coupled 1,2,3‐triazole analogues were prepared and evaluated for their epidermal growth factor receptor (EGFR) inhibitory profiles and antiproliferative activities. The confirmation of the structures of the synthesized compounds was done using spectroscopic techniques. Using the MTT assay, the in vitro cytotoxicity was investigated against three human cancer cell lines, MDA‐MB‐468, HepG‐2, and A549. Compound 8a had the highest anticancer activity against all cancer cell lines, with an IC 50 range of 1.02 ± 0.56–3.67 ± 0.07 μM. The EGFR inhibition of the most active compounds, 8a , 8b , 8d , 8f , and 8h was further assessed. In contrast to Erlotinib (IC 50 = 0.19 ± 0.07 μM), compounds 8b and 8h , demonstrated IC 50 values of 0.54 ± 0.18 and 0.33 ± 0.06 μM, respectively. Binding interactions showed that the synthesized compounds were involved in inhibiting the growth of cancer by blocking the EGFR enzyme (PDB:3W2Q). The DFT/B3LYP method functionalized with a 6–31 g(d, p) basis set was employed to calculate quantum parameters, MEP analysis, HOMO, and LUMO. Compounds 8b , 8g , and 8h have displayed good in silico ADMET properties. Compounds 8b , 8g , 8h , and 8j displayed good drug‐likeness scores (1.02, 1.09, 0.60, and 0.75) and none of the compounds can cross the blood–brain barrier because they are all outside the boiled egg yolk.

A series of biaryl piperidine derivatives 6-14 was synthesized and evaluated for antileishmanial efficacy against the Leishmania donovani strain Ag83. The Suzuki reaction of the bromo compound yielded biaryl compounds 6-8. Boc protection of 6-8 resulted in the formation of piperidine derivatives as hydrochloride salts (9-11), and subsequent ester hydrolysis gave pure biaryl amino acid derivatives (12-14). The target compounds 8-11 and 13 showed promising antileishmanial activity. The hydrochloride salts of biaryl piperidines, 9 and 10 exhibited the 60.2% and 57.2% inhibition respectively at 20 mu M concentration and further inhibited the proliferation by 63.7%, 64.0%, 64.7%, 64.8%, 69.2%, and 64.6, 64.8%, 64.8%, 66.4%, 67.9%, respectively, at 40, 80, 100, 150, and 300 mu M concentrations. The respective IC50 values for compounds 9 and 10 are 16 mu M and 17 mu M. The compounds chosen for this study were additionally analyzed through molecular docking, and the binding affinities correspond with the biological findings. The emergence of these new compounds will enable the development of new drugs for targeting Leishmaniasis.

A cost-effective and eco-compatible 1CaO-1.5MgO binary metal oxide (BMO-1) served as an efficient solid-base catalyst in the Knoevenagel condensation (KC) reaction of a range of aldehydes with active methylene reagents (i) malononitrile and (ii) ethyl cyanoacetate in water at room temperature (RT) to produce α,β-unsaturated compounds in purity with a good E-factor. We also report the ketone-malononitrile KC reaction and salicylaldehyde-malononitrile tandem KC-Michael addition effectively catalyzed by BMO-1. We report the synthesis of 31 α,β-unsaturated compounds that include 9 entirely new compounds under optimized conditions. We compared all catalyzed reactions with the "blank test" due to the high reactivity of active methylene reagents and emphasized the implication of the catalyzed aqueous KC reaction. We deduced the structure-activity relationship (SAR) between the catalyst and substrates, the plausible reaction mechanism, and the turnover frequency (TOF) data of the BMO-1 catalyst. For evaluation, we compared the efficiency of CaO, MgO, and 1.5CaO-1MgO (BMO-2), 1CaO-2MgO (BMO-3), and 1CaO-1MgO (BMO-4) catalysts in a model KC reaction. We prepared the MgO, CaO, BMO-1, and BMO-2 materials via an ultradiluted coprecipitation process and characterized the catalysts by X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET), CO2 temperature-programmed desorption (CO2-TPD), Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and transmission electron microscopy (TEM) techniques. The superior catalytic activity of BMO-1 is due to its high specific surface area of 97.6 m2/g, surface basicity of 152.4 μmol/g, and smaller particle size of 16.9 nm compared to the other three materials. Catalyst recycling experiments indicate that BMO-1 was stable for up to five cycles for the KC reaction. The BMO-1 spent catalyst analysis indicated the fundamental reason for its deactivation. We also report the optimized conditions for a selected KC reaction for upscaling (100 mmol).

Imines are certainly important constituents of many biomolecules, pharmaceuticals, agrochemicals, and fine chemicals. This review article highlights the standard protocols reported so far for the selective synthesis of imines via catalyzed and non-catalyzed (i) oxidative coupling of primary amines and (ii) oxidation of secondary amines in the presence of some competent/resourceful oxidants other than molecular O2 such as tert-butyl hydroperoxide (TBHP), H2O2, hypervalent iodines, persulfate, hypochlorite, electroactive species and graphene oxide. Indeed, the use of such oxidants offers a cost-effective experimental set-up, operational simplicity and also minimization of by-products. The cooperativity between catalyst, amine substrate, and oxidant is discussed in this review to understand the proposed mechanisms. Three consolidated data tables (Table 1, 2 & 3) are prepared to provide the summary of optimized reaction conditions (type of catalyst, type of oxidant, choice of solvent, amine-to-oxidant ratio, reaction time/temperature, conversion of amine, yield/selectivity of imine) of each article published to have a comparison.

This study explores an innovative biorefinery approach, synergizing state-of-the-art biomass conversion technologies to concurrently produce energy and valuable chemicals from abundant and renewable biomass feedstocks. Employing Ru/Al2O3-ZrO2 catalyst, Knoevenagel condensation yielded a remarkable 96% product yield with nearly 100% furfural conversion at room temperature and a short reaction duration. The research extends its scope by investigating time and temperature dependencies, optimizing the process for sustainability. Demonstrating versatility, the strategy accommodates various substrates. Catalyst recyclability was assessed over 6 cycles, revealing negligible performance decline, affirming the robustness of this catalytic system.

This review article describes the designing and aptness of diverse range of cerium-based catalysts for the oxidation of benzyl alcohols (Bz-OLs) in producing exclusively benzaldehydes (Bz-ALs) in the presence of eco-friendly oxidants. The discussion highlights the significance of surface and structural properties inherent to cerium-based catalysts, including the abundance of oxygen vacancies, the redox properties of Ce3+/Ce4+ couple, their acid-base characteristics and morphology influence, which play crucial roles in substrate adsorption, reorganization of bonding between substrate and oxidant in promoting selective oxidation reactions. The consolidated data tables (1-4) comprising the best conditions optimized with various ceria based heterogeneous reported so far between the years 2019-2024 is included in the following sections to assess the catalyst design and performance.

At 550 °C and atmospheric pressure, clean hydrogen was produced through CH4 cracking on a ceria modified silica supported Ni catalyst. A high proportion of Ni surface area on 20Ni/2wt%CeO2-SiO2demonstratedbetter H2 yields. The graphitic nature of the deactivated catalyst was established by TEM, XRD analyses and the distinction between ordered and disordered carbon was established by Raman spectroscopy. The high H2 yields produced by 20Ni/2wt%CeO2-SiO2catalyst was explained due to high nickel dispersion and an improved surface area of the nickel as assessed by H2 pulse chemisorption.

This study explores a rational synthesis of a molybdenum-promoted Ce-Si mixed oxide catalyst (MoO3/CeO2-SiO2) to regulate synergies between MoO3 and SiO2 dopant on CeO2, achieving high selectivity in solvent-free catalytic oxidative coupling of amines to imines using molecular O-2 as the oxidant. Comparative efficiency tests were conducted with bare CeO2, CeO2-SiO2, and MoO3/CeO2 catalysts. Characterization techniques, including XRD, Raman spectroscopy, N-2-adsorption-desorption analysis, FTIR, NH3-TPD, TEM, and XPS, were employed to assess textural properties, acidic features, promoter and dopant dispersion in CeO2 lattice, and oxygen defects. Mo/Ce-Si catalyst exhibited superior acidic sites and a higher concentration of Ce3+ ions (I-u/I-Total), indicating increased oxygen vacancies. This catalyst demonstrated exceptional performance in the oxidative coupling of benzylamine, providing higher conversion and selectivity to the corresponding imine. Remarkably, the Mo/Ce-Si catalyst maintained consistent performance over five recycling runs. The catalyst also proved effective for the selective oxidative coupling of various amine substrates with diverse steric and electronic properties. Experimental results confirmed a plausible reaction mechanism within the concise catalyst design.

Herein, the efficacy of WOx-promoted CeO2-SiO2 and CeO2-ZrO2 mixed oxide catalysts in the solvent-free selective oxidation of benzyl alcohol to benzaldehyde using molecular oxygen as an oxidant is reported. We evaluated the effects of the oxidant and catalyst concentration, reaction duration, and temperature on the reaction with an aim to optimize the reaction conditions. The as-prepared CeO2, CeO2-ZrO2, CeO2-SiO2, WOx/CeO2, WOx/CeO2-ZrO2, and WOx/CeO2-SiO2 catalysts were characterized by X-ray diffraction (XRD), N2 adsorption-desorption, Raman spectroscopy, temperature-programmed desorption of ammonia (TPD-NH3), X-ray photoelectron spectroscopy (XPS), and transmission electron microscopy (TEM). These characterisation results indicated that the WOx/CeO2-SiO2 catalyst possessed improved physicochemical (i.e., structural, textural, and acidic) properties owing to the strong interactivity between WOx and CeO2-SiO2. A higher number of Ce3+ ions (Iu'''/ITotal) were created with the WOx/CeO2-SiO2 catalyst than those with the other catalysts in this work, indicating the generation of a high number of oxygen vacancies. The WOx/CeO2-SiO2 catalyst exhibited a high conversion of benzyl alcohol (>99%) and a high selectivity (100%) toward benzaldehyde compared to the other promoted catalysts (i.e., WOx/CeO2 and WOx/CeO2-ZrO2), which is attributed to the smaller particle size of the WOx and CeO2 and their high specific surface area, more significant number of acidic sites, and superior number of oxygen vacancies. The WOx/CeO2-SiO2 catalyst could be quickly recovered and utilized at least five times without suffering any appreciable activity loss.

Adsorption of Fe(III) ions and Fe(III) complexes on selected adsorbents in aqueous solutions is reported. Fe(III) complexes with ribose, lactic acid, glycine and valine were prepared, and FTIR spectra validated their formation. The structural data of scanning electron microscopy (SEM) and X-ray diffraction (XRD) analysis also confirm the structure of the iron-ligand complexes and their adsorption on selected ligands (celite, cellulose, bentonite, activated carbon, carbon nanoparticles). Fe(III) adsorption from Fe−ligand complexes (FeLCs) on adsorbents in an aqueous solution was higher than the adsorption of metal ions alone. Compared with non-carbon adsorbents, carbon adsorbents carbon nano particles (CNP) and activated carbon (AC) showed higher adsorption of FeLCs. The atomic absorption spectroscopy (AAS) studies showed that the Fe−valine complex demonstrated the maximum adsorption (1719.18 ppm) compared to other samples. energy dispersive X-ray spectroscopy (EDS) studies confirmed a 2.16-fold increase in Fe(III)−Val complex adsorption compared with the pure metal ions. The current strategy provides an efficient proto-type to remediate Fe(III) contaminated water and to fortify Fe(III) through diet.

The mono or single oxides of alkaline earth metals such as CaO and MgO are a type of non-toxic and non-corrosive solid-base heterogeneous catalysts. Nevertheless, these mono oxide particles can agglomerate and form larger and less active particles at certain temperatures and reduces their catalytic activity. Therefore, the use of thermally stable CaO-MgO binary oxides is recommended. Further, the possible synergistic interactions between two metal centers provides cooperative catalytic behavior to improve catalytic activity compared to their single oxide counterparts. Therefore, the main theme of this review article is to highlight the ability of reported CaO-MgO based alkaline earth binary oxides as cost-effective and efficient solid-base catalysts in variety of organic transformations and to expand their scope in many other unexplored non-asymmetric organic transformations. Literature survey reveals that CMBOs are highly considerable in optimizing recognized organic transformations such as Transesterification, Knoevenagel/Aldol condensations, Isomerization, Oligomerization, Acetylation, Henry reaction, Alcoholysis, Aza-Michael addition, Cracking of Alkanes, H2-production via steam reforming, Photodegradation of organic pollutants and so forth. The literature survey further visualizes that the surface properties of CMBOs such as Brønsted/ Lewis’s basicity, surface area, particle size, structural diversity, Ca: Mg ratios and synergism between Ca and Mg in CMBOs are very useful to promote them as efficient catalysts compared to their single oxide counterparts (pure CaO and pure MgO). The rightness of proposed mechanisms of abovementioned organic reactions by CMBO catalysts is elicited by this review. Moreover, the precursors for CMBOs are inexpensive, highly abundant and eco-compatible. Apart from the catalytic applications, the suitability of the CMBOs in sorption studies including CO2 uptake, ethanol steam reforming, and heavy metal ion removal is also covered.

A new library of target compounds (9a-j) was designed, synthesized, and fully characterized by 1HNMR, 13CNMR, and mass spectroscopy techniques. The target compounds were screened for their cytotoxic properties against cancer cell lines Colo-205, MCF-7, A549, and A2780 by employing the MTT assay, using the etoposide as the positive control. Among the newly synthesized target compounds, four compounds 9b-9d and 9j exhibited superior cytotoxic properties to the reference standard (etoposide). In particular, compound 9b was more cytotoxic against all four cell lines with IC50 in the range of 0.016 to 0.17 mu M. Further 9b is more selective toward A549 and followed by MCF-7. Molecular docking studies of all the target compounds were carried out against hDHFR to see the binding interactions and binding affinities. Ligands 9b and 9c have the highest binding affinities toward hDHFR and these results substantiate the experimental findings. The MEC was analyzed for the most potent compounds 9b and 9c. All the ligands have passed the Insilico ADME properties and haven't violated more than one Ro5.

A novel series of oxazolyl-pyrimidine derivatives (11a-j) have been synthesized and structures were confirmed by spectral data. The synthesized compounds were assessed for cytotoxic profile towards human cervix cancer (SiHa), lung cancer (A549), breast cancer (MCF-7), and colon cancer (Colo-205) cell lines by employing MTT assay and using etoposide as the positive control. The heteroaryl compounds having the terminal pyridyl (11a) and thiazolyl (11b) groups showed superior cytotoxic potency against cervix and lung cancer cell lines and varying methoxy substituted derivatives 11c-11e have excellent to good cytotoxic properties. Compound 11a and 11b have IC50 values in the range of 0.01 +/- 0.0034 to 0.17 +/- 0.059 mu M and 0.10 +/- 0.038 to 0.66 +/- 0.077 mu M respectively in the tested cell lines. The selected compounds 11a and 11b were studied by molecular docking to assess the binding interactions, binding energies, and possible mechanisms. The in-silico ADME properties were calculated and all the compounds have the desired properties of drug-like molecules. The toxicity results indicate that all the compounds are free from toxicity except 11j, which has high tumorigenic properties. The optimized structure, energies of frontier molecular orbitals, molecular electrostatic potential, and NLO parameters for compound 11a were determined using DFT/B3LYP level with a 6-311+ + G(d,p) basis set.

Upgrading biomass-derived levulinic acid (LA) with greater carbonyl (CO) group activation is crucial in converting biomass and its derivatives into valuable biochemicals and biofuels.

A hybrid molecule of isoxazole and thiazolidine-4-one, 2-(4-fluorophenyl)-3-(5-methylisoxazol-3-yl)thiazolidin-4-one (3) was synthesized and characterized unambiguously using 1HNMR, 2D NMR, 13CNMR, IR, and LCMS. The extensive molecular and electronic parameters for compound 3 were calculated by using the DFT/B3LYP/6–311++G(d,p) level. The target compound 3 was evaluated for in vitro anticancer activity against HeLa, MCF7, A549, and HEK293 cell lines. Molecular docking studies in the active site of EGFR revealed the key interactions of compound 3 and the insilico ADME properties were calculated using SwissADME.

We have developed a new series of simple biaryl piperidine derivatives (11-19) based on biaryl naphthylisoquinoline alkaloid Ealamine-A. The target compounds were synthesized, analyzed by spectral data, and evaluated for antileishmanial activity against Leishmania donovani strain Ag83 by MTT assay. The compounds have shown the best to moderate antileishmanial activity. The 5'-fluoro-2'-methoxyphenyl derivative 14 and 3',5'-difluorophenyl derivative 16 have inhibited the promastigotes by 86 % and 85 % after 24 h and 92 % and 91 % after 48 h incubation, respectively, at 400 μM concentration. The % inhibition was lower with the lowering of the concentration and increased with the incubation time. Compounds 12, 15, and 18 have solubility issues and proved to be less active than the rest of the compounds. Molecular docking studies were performed on selective active compounds and the results indicate that these compounds may act by binding to the Leishmanolysin and the docking scores are in good correlation with the antileishmanial activity. These results provide an initial insight into the design of new therapeutics for neglected tropical diseases.