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The Michael addition reaction of barbituric acid with chalcones incorporating the indole scaffold was achieved by using a highly efficient bimetallic Iron–palladium catalyst in the presence of acetylacetone (acac). This catalytic approach produced the desired products in a simple operation and low catalyst loading with acceptable yield of the new hybrids. All tested compounds were subjected for biological activity on α‐glucosidase and α‐amylase. The results revealed that all synthesized compounds exhibited very good activity against both enzymes when compared to positive control (acarbose). Moreover, compound 5o showed the best activity whereas its IC50 (μM) are 13.02+0.01 and 21.71+0.82 for α‐glucosidase and α‐amylase respectively. Both compounds 5o and 5l exhibited high similarity in binding mode and pose with amylase protein (4UAC). The obtained data may be used for developing potential hypoglycemic agents.

Anticancer therapeutics with profiles of high potency, low toxicity, and low resistance is of considerable interest. A new series of functionalized spirooxindole linked with 3-acylindole scaffold is reported, starting from chalcones derived from 3-acetyl indole with isatin, and l-4-thiazolidinecarboxylic acid. The reactions proceeded regioselectivity, stereoselectivity, without side products in high yield (71–89%). The new spirooxindole hybrids have been evaluated in vitro for their antiproliferative effects against colon cancer (HCT-116), hepatocellular carcinoma (HepG2) and prostate cancer (PC-3). The selectivity of their activity was evaluated. Some of the synthesized compounds showed considerable anticancer activities. Compound 4k proved to retain a high cytotoxic activity and selectivity against colon cancer cells HCT-116 (IC50 = 7 ± 0.27 µM, SI: 3.7), and HepG2 (IC50 = 5.5 ± 0.2 µM, SI: 4.7) in comparison to (IC50 = 12.6 ± 0.5, SI: 0.4 and 5.5 ± 0.3 µM, SI: 0.9, respectively). Compound 4k was less active (IC50 = 6 ± 0.3 µM, SI: 4.3) than cisplatin (IC50 = 5 ± 0.56 µM, SI: 1.0) but showed greater selectivity towards prostate cancer cells PC-3 in comparison to cisplatin. The details of the binding mode of the active compounds were clarified by molecular docking. Ligand Efficiency (LE) and Ligand Lipophilic Efficiency (LLE) were evaluated and revealed that compound 4k had acceptable value.

N-(Anthracen-9-ylmethyl)-N-methyl-2-(phenylsulfonyl)ethanamine 3 has been synthesized via the aza-Michael addition approach by reaction of the corresponding amine with the vinyl sulfone derivative under microwave conditions. The structure of the aza-Michael product 3 is elucidated by X-ray crystallography. The study of molecular packing by employing the Hirshfeld analysis indicates that the percentages of O&hellip, H, C&hellip, H and H&hellip, H contacts are 16.8%, 34.1% and 48.6%, respectively, where the O...H hydrogen bonds have the characteristics of short and strong contacts while the C...H contacts are considered weak. Density functional theory (DFT) investigations show that the aza-Michael product 3 is polar with a net dipole moment of 5.2315 debye.

Urease is a therapeutic target associated with several important diseases and health problems. Based on our previous work on the inhibition of glucosidase and other enzymes and exploiting the privileged structure assigned to the (thio)barbiturate (pyrimidine) scaffold, here we tested the capacity of two (thio)barbiturate-based compound collections to inhibit urease. Several compounds showed more activity than acetohydroxamic acid as a standard tested compound. In addition, by means of a conformational study and using the Density Functional Theory (DFT) method, we identified energetically low-lying conformers. Finally, we undertook a docking study to explore the binding mechanism of these new pyrimidine derivatives as urease inhibitors.

A green, simple and efficient protocol for the synthesis of the two new barbituric acid derivatives; 4 and 5 is described. One pot fashion of 2 mol of barbituric acid derivatives with 3-fluorobenzaldehyde in green solvent (H2O) providing compound 4. Reaction of equimolar of barbituric acid derivatives, dimedone and 4-(trifluoromethyl)benzaldehyde gave compound 5. Using the density functional theory at the B3LYP level and 6-311G(d,p) as basis set, the molecular structures of the studied compounds were optimized. The minimum energy structures have geometrical parameters correlated well with the experimental data. 4 has two barbituric acid moieties more deviated from the planarity than the barbiturate ring in 5. The latter exists in the enol form and it is stabilized by strong intramolecular hydrogen bonding interactions. The NBO analysis revealed the presence of significant π-π* intramolecular charge transfer in this ring, while this effect is absent in 4. The electronic spectra of the studied compounds were investigated experimentally and theoretically using the TD-DFT method. The compound which has one more conjugated ring (5) has one more band at longer wavelength of 318 nm (calc. 313.5 nm) which is assigned to H→L (93%) excitation. The anti-oxidant activity as reactive oxygen scavenger was examined in this research. The NO and DPPH radical scavenger assays were carried out. The results clearly demonstrated that compounds 4 and 5 possess a significant effect as reactive oxygen scavenger compared with the standard drugs. The ligand efficiency (LE) metrics as LE value and ligand lipophilic efficiency (LLE) were calculated and they showed that compound 4 has better character as drug likeness candidate rather than compound 5. The docking study of the compounds showed that compound 4 docked with the receptor (PDB ID: 3JSW) through lipophilic-lipophilic interaction. Interestingly, compound 5 represent dissimilarity from compound 4.

One-pot synthesis of three enaminones, (E)-1-(4-chlorophenyl)-3-morpholinoprop-2-en-1-one 1, (E)-1-(4-chlorophenyl)-3-(4-methylpiperazin-1-yl)prop-2-en-1-one 2, and (E)-1-(4-chlorophenyl)-3-(pyrrolidin-1-yl)prop-2-en-1-one 3 were achieved. The synthetic protocol via three components reaction of p-chloroacetophenone with DMFDMA (N,N-dimethylformamid-dimethylacetal) and the corresponding secondary amines (morpholine/N-methylpiperazine/pyrrolidine) in dioxane under heating for 2.5&ndash, 4 h at 102 &deg, C yielded the requisite enaminones. This protocol has the advantage of no separation of intermediate, no need for column purification with quantitative yield for the target compounds. The chemical features of the &beta, enaminones 1&ndash, 3 were assigned by NMR. &beta, Enaminones 1, and 2 were assigned by single crystal X-ray diffraction technique. The intermolecular interactions in the crystal structures were analyzed quantitatively using Hirshfeld analysis. The Cl&hellip, H and O&hellip, H hydrogen bonds are common in both compounds while the C-H&hellip, &pi, and N&hellip, H contacts are more significant in 2 than 1. DFT studies were investigated to show the electronic and spectroscopic properties (NMR and UV-Vis) of the studied systems.

A one-pot, single-step, and an atom-economical process towards the synthesis of highly functionalized spirooxindoles analogues was efficiently conducted to produce a satisfactory chemical yields (70&ndash, 93%) with excellent relative diastereo-, and regio-selectivity. An in vitro antiproliferative assay was carried out on different cancer cell lines to evaluate the biological activity of the synthesized tetrahydro-1&rsquo, H-spiro[indoline-3,5&rsquo, pyrrolo[1,2-c]thiazol]-2-one 5a&ndash, n. The prepared hybrids were then tested in vitro for their antiproliferative effects against three cancer cell lines, namely, HepG2 (liver cancer), MCF-7 (breast cancer), and HCT-116 (colon cancer). The spirooxindole analogue 5g exhibited a broad activity against HepG2, MCF-7, and HCT-116 cell lines of liver, breast, and colorectal cancers when compared to cisplatin. Modeling studies including shape similarity, lipophilicity scores, and physicochemical parameters were calculated. The results of this study indicated that spirooxindole analogue 5g retained a good physiochemical parameters with acceptable lipophilicity scores.

A new series of thiobarbituric (thiopyrimidine trione) enamine derivatives and its analogues barbituric acid derivatives was synthesised, characterised, and screen for in vitro evaluation of α-glucosidase enzyme inhibition and anti-glycation activity. This series of compounds were found to inhibit α-glucosidase activity in a reversible mixed-type manner with IC50 between 264.07 ± 1.87 and 448.63 ± 2.46 µM. Molecular docking studies indicated that compounds of 3g, 3i, 3j, and 5 are located close to the active site of α-glucosidase, which may cover the active pocket, thereby inhibiting the binding of the substrate to the enzyme. Thiopyrimidine trione derivatives also inhibited the generation of advanced glycation end-products (AGEs), which cause long-term complications in diabetes. While, compounds 3a–k, 5, and 6 showed significant to moderate anti-glycation activity (IC50 = 31.5 ± 0.81 to 554.76 ± 9.1 µM).

Indole containing compounds have acquired conspicuous significance due to their wide spectrum of biological activities. Synthesis of a series of enantiomerically pure indole derivatives 3a-r via Friedel–Crafts alkylation of indole 1 with enones 2a-r were described here. The products were isolated in a moderate to excellent yields (upto 89%) with excellent enantioselectivities (upto 99.9% ee). These compounds 3a-r were evaluated for their in vitro α-glucosidase inhibitory activity and some of them were identified as potent inhibitors (IC50 = 4.3 ± 0.13–43.9 ± 0.51 μM) with several fold higher activity than the clinically used α-glucosidase inhibitor, acarbose (IC50 = 840 ± 1.73 μM). To the best of knowledge, this is the first report of the propanone substituted indole ring containing compounds by in vitro α-glucosidase enzyme inhibition.

A one-pot multi-component reaction of N,N-dimethylbarbituric acid,1,3-cyclohexanedione and 3-bromobenzaldehyde in H2O mediated by diethyl amine as a base affords a new barbituric acid–cyclohexanedione hybrid. The reaction proceeds smoothly, efficiently, and in high yield. The molecular structure of this compound was determined by single-crystal X-ray diffraction crystallography and spectrophotometric analyses. Of the nine possible isomers of the studied compound, the B3LYP/6-31G(d,p) method predicts that form B, in which the two OH groups are involved in significant intramolecular H-bonding interactions with the neighboring carbonyl O atom, is the most stable form in the gas phase. The X-ray structure reveals a different isomer due to intermolecular interactions caused by molecular packing in the crystal, which stabilizes the solid-state structure. Hirshfeld surface analysis of the molecular packing indicates that the H···O interactions are the primary contributor (24.5%) to the intermolecular stabilization in the crystal.

In this work, polycyclic heterocycles containing spirooxindole, pyrrolidine, and thioxothiazolidin-4-one rings have been synthesized via the regioselective 1,3-dipolar cycloaddition of azomethine ylide, which is generated in situ by the condensation of the dicarbonyl compound isatin and the secondary amino acid ( l -proline), with 5-arylidine-2-thioxothiazolidin-4-one as the dipolarophile. The structure of the synthesized compounds 4a and 4b were determined by using X-ray single crystal diffraction, and also, Hirshfeld surface analysis were reported. Their geometric parameters were calculated using density functional theory at the B3LYP/6-311G (d,p) level of theory. Both compounds showed antimicrobial and antifungal activity better than selected standards (ampicillin and gentamicin in case of antibacterial activity and Amphotericin A and fluconazole in case of antifungal activity). Molecular docking study of the synthesized compounds indicated that phenyl group plays an important role in determination of compound interaction inside the receptors.

Spirooxindole is a promising chemo therapeutic agent. Possible targets include cancers of the liver, prostate, lung, stomach, colon, and breast. Here, we demonstrate a one-pot three-component reaction via a [3 + 2] cycloaddition/ring contraction sequence of a dipolarophile (activated alkene) with in situ-generated azomethine ylide (1,3-dipoles) without the use of any catalyst. The reaction provides efficient access to synthetically useful and biologically important spirooxindoles in high yield (69–94%) with high diastereoselectivity. The synthesized compounds were subjected to cytotoxicity evaluation using colorectal cancer (HCT-116), hepatocellular carcinoma (HepG2), and prostate cancer (PC-3) cells. Compounds 4i, 4j, and 4k showed potent cytotoxic activity and high selectivity against HCT-116 cells when compared to cisplatin. Meanwhile compound 4d retained high cytotoxic activity and selectivity against HepG2 and PC-3 cells in comparison to cisplatin. The mechanism of compound 4d was further studied using phosphodiesterase 1 enzyme and showed 74.2% inhibitory activity. A possible binding mode for compound 4d to PDE-1 was investigated by molecular modeling using OpenEye software. Pose predictions for the active compounds were demonstrated by ROCS alignments. Compound 4d has a special geometry and differs from other active compounds.

The preparation of [NHC·H][Pd(η3-R-allyl)Cl2] complexes is disclosed and represents a facile, atom-economical, environmentally friendly and rapid synthesis. These palladates are immediate synthetic precursors to the well-known [Pd(NHC)(η3-R-allyl)Cl] complexes. Their activation leading to catalytically relevant species has been studied in the Suzuki–Miyaura reaction. The need for an activation step prior to the catalysis was examined. The reaction scope showcases its ease and breadth in terms of functional group tolerance. Electron-donating and electron-withdrawing aryl chlorides and bromides were coupled effectively as well as heteroatom-containing and sterically hindered aryl halides. The catalytic reaction was conducted in ethanol with a weak and inexpensive inorganic base.

A series of new spiro-heterocycles engrafted spirooxindole/pyrrolidine/thiochromene scaffolds was synthesized by the three-component 1,3-dipolar cycloaddition reactions in a fully controlled regio- and stereo-selective fashion. Condensation of several substituted isatin derivatives with L-proline generated the azomethine ylides which subsequently reacted with chalcones based thiochromene scaffold, and finally afforded the target spiro-compounds. This simple protocol furnished a structurally complex, biologically relevant spiro-heterocycles in good yields through a one-pot process. All synthesized chalcone-based thiochromene, along with the spirooxindole/pyrrolidine/thiochromene scaffolds, were tested for their anticancer activity against four cancer cell lines (PC3, HeLa, MCF-7, and MDA-MB231). Toxicity of these compounds was also evaluated against human fibroblast BJ cell line, and they appeared to be not cytotoxic. For the prostate cancer (PC3) cell line, the most active hybrid, among synthesized series, was compound (7f, IC50 = 8.7 ± 0.7 µM). The most potent spirooxindole/pyrrolidine/thiochromene hybrid against cervical (HeLa) cancer cells was compound (7k, IC50 = 8.4 ± 0.5 µM) having chlorine and p-trifluoromethyl substituents attached to phenyl rings. Finally, against the MCF-7 and MDA-MB231 breast cancer cell lines, compound (7d) was the most active member of this series (IC50 = 7.36 ± 0.37, and 9.44 ± 0.32 µM, respectively).

Barbiturate derivatives are privileged structures with a broad range of pharmaceutical applications. We prepared a series of 5-monoalkylated barbiturate derivatives (3a–l) and evaluated, in vitro, their antioxidant (DPPH assay), and α-glucosidase inhibitory activities. Compounds 3a–l were synthesized via Michael addition. The structure of compound 3k was determined using X-ray single-crystal diffraction, and geometric parameters were calculated using density functional theory at the B3LYP/6-311G(d,p) level of theory. Further, the structural analysis of 3k were also investigated. Biological studies revealed that compounds 3b (IC50 = 133.1 ± 3.2 μM), 3d (IC50 = 305 ± 7.7 μM), and 3e (IC50 = 184 ± 2.3 μM) have potent α-glucosidase enzyme inhibitors and showed greater activity than the standard drug acarbose (IC50 = 841 ± 1.73 μM). Compounds 3a–3i were found to show weak antioxidant activity against 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radicals (IC50 = 91 ± 0.75 to 122 ± 1.0 μM) when tested against a standard antioxidant, gallic acid (IC50 = 23 ± 0.43 μM).

The aim of this research is to evaluate for the first time the in vitro leishmanicidal activity and inhibition of α-glucosidase and β-glucuronidase of new gold(I) and gold(III) complexes involving N-heterocyclic carbene (NHC) ligands, with the general formula [Au(X)n(NHC)R2][BF4] (X=Cl, OAc, R=various aromatic and aliphatic substituents). The Au(III) complexes were shown to have a significant antileishmanial activity, and were also found to be more potent inhibitors of α-glucosidase and β-glucuronidase enzymes than the standard drugs. Some complexes were also identified as potent anti-inflammatory agents with activity comparable to that of tested standard drugs, allopurinol and ibuprofen. These gold complexes were also evaluated for their in vitro cytotoxic activity against HeLa (cervical cancer), MCF-3 (breast cancer), and 3T3 (mouse fibroblast) cell lines.

Two new malonamide derivatives were synthesized via the Michael addition of N1,N3-di(pyridin-2-yl)malonamide to α,β-unsaturated ketones using a 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) catalyst at room temperature. All reactions efficiently furnished the desired malonamide derivatives, which differed only in their substitution on one phenyl group, with one derivative bearing a bromine substituent and the other bearing a methyl group. The structures of newly synthesized compounds were then elucidated by single-crystal X-ray diffraction, infrared spectroscopy, NMR spectroscopy, mass spectrometry, and elemental analysis. In addition, the synthesized compounds were evaluated for their in vitro cytotoxicity against cancer cell lines and for α-glucosidase inhibition. The target compounds exhibited enhanced α-glucosidase inhibition activity (i.e., IC50 = 12.8 ± 0.1 and 28.4 ± 0.2 μM) compared to the common drug acarbose (IC50 = 840 ± 1.73 μM). Both compounds were found to be non-cytotoxic against H460 (lung carcinoma) and T3T (normal fibroblast) cell lines. In addition, the bromo-substituted derivative exhibited weak cytotoxic against cervical cancer HeLa (IC50 = 13.8 ± 0.4 μM) and breast cancer MCF-7 (IC50 = 21.11 ± 0.88 μM) cell lines, while the methyl-substituted derivative showed weak cytotoxicity against the MCF-7 cell line (IC50 = 47.9 ± 0.7 μM). Density functional theory (DFT) B3LYP/6-311G(d,p) calculations were employed to examine the molecular structures and electronic properties of the prepared compounds. As expected, the bromo-derivative (2.2377 D) exhibited a higher polarity than the methyl-derivative (1.9160 D). Furthermore, the HOMO and LUMO diagrams were constructed and the electronic spectra of both compounds were assigned using time-dependent (TD)-DFT calculations. Finally, the calculated NMR chemical shifts correlated well with the experimental data.

The one-pot synthesis reaction of barbituric acid derivative, 1,3-cyclohexandione, and 4-fluorobenzaldehyde in water mediated by NHEt2 as base afforded 4 with excellent yield. The synthesized compound was characterized by spectrophotometric tools as well as X-ray single crystal diffraction technique. The stability of the nine possible isomers of the synthesized compound was studied using the B3LYP method and 6-31G(d,p) basis set. The electronic and spectroscopic properties of the most stable isomer were predicted. The UV–Vis absorption spectrum displayed two bands at 203 and 257 nm in the solvent chloroform. The latter was calculated at 235.6 nm (f = 0.1995) in the gas phase due to H-2→L (42%) and H-1→L+2 (14%) excitations. In solution, using chloroform as a solvent, a slight bathochromic shift to 237.6 nm with an increase in the absorption intensity (f = 0.2898) was predicted. The molecular orbital energy level diagram of this transition band was characterized mainly by π-π* transitions. The 13C and 1H NMR chemical shifts correlated well with the experimental data. The correlations had higher correlation coefficients (R2) when solvent effects were considered. The atomic charges were calculated using natural population analysis and the charged regions were presented using a molecular electrostatic potential (MEP) map. The synthesized compound was examined as a hypoglycemic agent via inhibition of α-glucosidase and β-glucuronidase enzymes. Its inhibitory activity against α-glucosidase was 10 times greater than the inhibitory activity of the standard drug acarbose (IC50 77.9 ± 0.3 μM and 840 ± 1.73 μM, respectively). Moreover, the target compound was evaluated for anticancer activity against MCF-7, H460, 3T3, and Hela cell lines. It demonstrated inhibitory activity against the MCF-7 and H460 cell lines with IC50 5.80 ± 0.12 and 19.6 ± 0.5 μM, respectively, in comparison to doxorubicin. The docking study was performed using the OpenEye program.

Diethylamine catalyzed tandem Knoevenagel–Michael reactions have been carried out in aqueous medium as an efficient, greener and cost effective process for the simple one-pot synthesis of bis-dimedone derivatives. Reaction of substituted aromatic aldehyde (1 equiv.) and dimedone (2 equiv.), in the presence of aqueous diethylamine medium at room temperature provides bis-dimedone derivatives 3a–n in excellent yields (87–95%) within a very short reaction time (15–60 min). All the bis-dimedone derivatives were obtained in high purity and the products were fully characterized by physical and spectroscopic data. The structures of compounds 3b,c were elucidated by single crystal X-ray diffraction technique. Compound 3b crystallizes in the monoclinic space group P 21/n with a = 10.2895(9) A , b = 18.0995(15) A , c = 15.8615(13) A , α = 90°, β = 107.975(2)°, γ = 90°, V = 2809.8(4) A 3 , and Z = 4. Compound 3c crystallizes in the monoclinic space group P 21/n with a = 10.2816(16) A , b = 18.080(3) A , c = 15.637(2) A , α = 90°, β = 107.076(4)°, γ = 90°, V = 2778.6(7) A 3, and Z = 4. The use of inexpensive, eco-friendly and readily available reagents, easy work-up, and high purity products makes the procedure a convenient and robust method for the synthesis of tandem Knoevenagel–Michael adducts.

C20H22N2O6, monoclinic, P21/c (no. 14), a = 8.6657(6) Å, b = 18.6201(14) Å, c = 22.3583(18) Å, β = 91.808(3)°, V = 3605.9(5) Å3, Z = 8, R gt(F) = 0.067, wR ref(F 2) = 0.177, T = 100(2) K.

The one-pot fashion of three multi-component reaction provides the desired hydroacridinone-based hydrazino-s-triazine scaffold 4. Compound 4 was crystallized in an orthorhombic crystal system and Pbca space group with a = 11.6271(2) &Aring, b = 18.2018(4) &Aring, c = 32.4721(6) &Aring, and &alpha, = &beta, = &gamma, = 90&deg, with one formula unit per asymmetric unit and eight molecules per unit cell. Additionally, structural features, Hirshfeld surfaces, and DFT studies were also investigated. Its packing in the crystal is controlled by H&hellip, H (63.4%), O&hellip, H (12.7%), Cl&hellip, H (7.2%), N&hellip, H (4.7%), and C&hellip, H (10.2%) contacts, where the O&hellip, H and Cl&hellip, H contacts were found the strongest. In vitro urease inhibition evaluation showed that the hydroacridinone-based hydrazino-s-triazine is more active (IC50 = 17.9 &plusmn, 0.47 &micro, M) than the standard acetohydroxamic acid (IC50 = 20.3 &plusmn, 0.43 &micro, M).

Inhibition of &alpha, amylase and &alpha, glucosidase by specified synthetic compounds during the digestion of starch helps control post-prandial hyperglycemia and could represent a potential therapy for type II diabetes mellitus. A new series of spiroheterocyclic compounds bearing oxindole/benzofuran/pyrrolidine/thiazolidine motifs were synthesized via a 1,3-dipolar cyclo-addition reaction approach. The specific compounds were obtained by reactions of chalcones having a benzo[b]furan scaffold (compounds 2a&ndash, f), with a substituted isatin (compounds 3a&ndash, c) and heterocyclic amino acids (compounds 4a,b). The target spiroindolone analogues 5a&ndash, r were evaluated for their potential inhibitory activities against the enzymes &alpha, glucosidase. Preliminary results indicated that some of the target compounds exhibit promising &alpha, glucosidase inhibitory activity. Among the tested spiroindolone analogues, the cycloadduct 5r was found to be the most active (IC50 = 22.61 &plusmn, 0.54 &mu, M and 14.05 &plusmn, 1.03 &mu, M) as &alpha, glucosidase inhibitors, with selectivity indexes of 0.62 and 1.60, respectively. Docking studies were carried out to confirm the binding interaction between the enzyme active site and the spiroindolone analogues.

An efficient and practical method for the synthesis of 2,6-diaryl-4-oxo-N,N&prime, di(pyridin-2-yl)cyclohexane-1,1-dicarboxamide is described in this present study, which occurs through a double Michael addition reaction between diamide and various dibenzalacetones. The reaction was carried out in dichloromethane (DCM) in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). The anticancer activities of the synthesized compounds were evaluated in several cancer cell lines, including MCF-7, MDA-MB-231, SAS, PC-3, HCT-116, HuH-7 and HepG2 cells. From these experiments, we determined that MDA-MB-231 was the most sensitive cancer cell line to the compounds 3c, 3e, 3d, 3j and 3l, which exhibited variable anticancer activities (3l [IC50 = 5 &plusmn, 0.25 &micro, M] &gt, 3e [IC50 = 5 &plusmn, 0.5 &micro, 3c [IC50 = 7 &plusmn, 1.12 &micro, 3d [IC50 = 18 &plusmn, 0.87 &micro, 3j [IC50 = 45 &plusmn, 3 &micro, M]). Of these, 3l (substituted p-trifluoromethylphenyl and chloropyridine) showed good potency (IC50 = 6 &plusmn, 0.78 &micro, M) against HCT-116 colorectal cancer cells and exhibited high toxicity against HuH-7 liver cancer cells (IC50 = 4.5 &plusmn, 0.3 &micro, M). These values were three times higher than the values reported for cisplatin (IC50 of 8 &plusmn, 0.76 and 14.7 &plusmn, M against HCT-116 and HuH-7 cells, respectively). The highest &alpha, glucosidase inhibitory activity was detected for the 3d, 3i and 3j compounds. The details of the binding mode of the active compounds were clarified by molecular docking studies.

This work deals with the synthesis and characterization of the novel 5-((5-chloro-1H-indol-2-yl)methylene)-1,3-diethyl-2-thioxodihydro-pyrimidine-4,6(1H,5H)-dione π-bridge (D–A–D) donor–acceptor–donor compound. Its exo-isomer structure has been proven by XRD-single-crystal analysis for the first time. The IR, UV–Vis., MS, CHN-, 1H and 13C NMR analysis were also carried out. The DFT-optimized structural-parameters were matched with the XRD-crystallographic data. The experimental-XRD-interactions in the lattice were compared to the computed Hirshfeld analysis (HSA), MEP map and Mulliken charge population. The DFT/6-311G(d) calculations like IR/B3LYP, TD-SCF, HOMO–LUMO, GRD and GIAO-NMR have been compared to their corresponding experimental parameters. Non-linear optical (NLO) crystal theoretical-analysis was carried out then compared to urea reference. The compound thermal activity was evaluated in an open-atmosphere by TG/DTG analysis.

A new unexpected hybrid based on the arylidene-thiazolidinone and 1,3,4-thiadiazole scaffolds via combined S-alkylation and Smiles rearrangement dual protocols. The one-pot reaction of arylidene-thiazolidinone with the hydrazonoyl chloride in a basic medium (Et3N) with benzene as solvent afforded the discovered compound at room temperature (25 °C). The molecular architecture of the designed hybrid were assigned based on the spectrophotometric tools. Based on Hirshfeld analysis, the molecules are connected by short O…H (19.6%), S…H (7.3%), H…C (20.1%), and C…C (0.7%) interactions. Density-functional theory (DFT) calculations indicated polar molecules (7.595 Debye). Its structure is stabilized by different σ-σ*, π→π*, n→σ*, and n→π* intramolecular charge transfer (IMCT) processes. The two longest wavelength bands observed in the UV–Vis spectra of diethyl(S,Z)-2-(2-(5-(4-hydroxybenzylidene)-4-oxo-4,5-dihydrothiazol-2-yl)-2-phenylhydrazinyl)-3-phenyl-2,3-dihydro-1,3,4-thiadiazole-2,5-dicarboxylate 3 were calculated at 364.0 (HOMO→LUMO+1) and 305.1 nm (HOMO-2→LUMO), which considerably agree with the experimental data.

The nitrogen containing spiro-heterocycle is one of the privileged synthetic motif that constitutes various naturally occurring molecules and displays a broad range of pharmaceutical and biological activities. A new methodology was developed for the synthesis of 2,4-diazaspiro[5.5]undecane-1,3,5,9-tetraones spiro-heterocyclic derivatives via cascade cyclization of [5+1] double Michael addition reaction of N,N-dimethylbarbituric acid with the derivatives of diaryldivinylketones in the presence of diethylamine at ambient temperature. The developed protocol is highly capable of furnishing diazaspiro[5.5]undecane derivatives 3a–m in excellent yields (up to 98%), from easily accessible symmetric and non-symmetric divinylketones 2a–m, containing aryl and heteroaryl substituents. The diazaspiro-heterocyclic structure was mainly elucidated by NMR and X-ray crystallographic techniques. The single-crystal X-ray studies revealed that, the cyclohexanone unit of spirocycles often prefers a chair conformation rather than twisted conformation. The intermolecular hydrogen bonding and CArH⋯π, π–π stacking interactions driving forces are mainly responsible for the crystal packing.

The gem-aminals of 1,2-dimorpholinoethane (1) and 1-morpholino-3-morpholinium bromide propane (2) were synthesized by reaction of two molar ratio of morpholine with the halogenating agents in the presence of basic condition (K2CO3) in acetone at room temperature (RT) overnight. The structures of the centro-symmetric compound 1 and the morpholinium salt derivative 2 were assigned unambiguous by single crystal X-ray diffraction analysis and compared with the 1,2-di(pyrrolidin-1-yl)ethane 3 and 1,2-di(piperidin-1-yl)ethane 4. The 1,2-dimorpholinoethane molecule has a center of symmetry at the midpoint of the C-C bond of the ethyl moiety leading to two equivalent halves. It crystallized in monoclinic crystal system and P21/n space group, while the unit cell parameters are determined to be a = 6.0430(3), b = 8.0805(3), c = 11.1700(4) &Aring, and &beta, = 97.475(2)&deg, with unit cell volume of 540.80(4) &Aring, 3 and Z = 2 at 170(2) K. The less symmetric analogue 2 crystallized in the lower space group P21 with unit cell parameters of a = 6.37450(10), b = 11.1378(2), c = 9.6549(2) &Aring, = 93.358(2)&deg, while the unit cell volume is 684.30(2)&Aring, 3 at 120(2) K. Using Hirshfeld analysis, the molecules of 1 are mainly packed by weak N&hellip, H (4.2%), O&hellip, H (16.8%), and H&hellip, H (79.0%) interactions. In contrast, the molecules of 2 are packed by significantly short O&hellip, H (14.4%) and Br&hellip, H (11.6%) interactions in addition to the relatively long H&hellip, H (73.3%) interactions. DFT calculations predicted the molecular geometry of the studied compounds showing a good agreement with the experimental X-ray structures. Due to symmetry considerations, compounds 1, 3, and 4 are nonpolar with zero dipole moment, while the less symmetric molecule 2 has a dipole moment of 6.914 Debye. Their electronic aspects, such as natural population charges, HOMO, and LUMO energies as well as the corresponding reactivity descriptors, were also calculated and discussed.

A series of new oxindole-based spiro-heterocycles bearing the benzo[b]thiophene motif were synthesized via a 1,3-dipolar cycloaddition reaction and their acetylcholinesterase (AChE) inhibitory activity was evaluated. All the synthesized compounds exhibited moderate inhibitory activities against AChE, while IIc was found to be the most active analog with an IC50 value of 20,840 &micro, M&middot, L&minus, 1. Its molecular structure was a 5-chloro-substituted oxindole bearing benzo[b]thiophene and octahydroindole moieties. Based on molecular docking studies, IIc was strongly bound to the catalytic and peripheral anionic sites of the protein through hydrophilic, hydrophobic, and &pi, stacking interactions with Asp74, Trp86, Tyr124, Ser125, Glu202, Ser203, Trp236, Trp286, Phe297, Tyr337, and Tyr341. These interactions also indicated that the multiplicity of the IIc aromatic core significantly favored its activity.

A new Pd(II) complex, [Pd(Triaz)Cl], with the hydrazono-s-triazine ligand, 2,4-di-tert-butyl-6-((2-(4-morpholino-6-(phenylamino)-1,3,5-triazin-2-yl)hydrazono)methyl)phenol (HTriaz), was synthesized by the reaction of PdCl2 with the organic ligand (1:1) in acetone under isothermal conditions. The molecular structure of the [Pd(Triaz)Cl] complex was determined using FTIR and 1H NMR spectroscopic techniques, and single-crystal X-ray diffraction. Moreover, using Hirshfeld surface analysis, the percentages of the intermolecular interactions were determined. The obtained values were 60.6%, 11.6%, 8.1%, 3.6%, and 5.0% for the H⋯H, C⋯H, O⋯H, N⋯H, and Cl⋯H interactions, respectively. Among them, the O⋯H, C⋯H and C⋯N interactions are considered extremely important. Natural bond orbital calculations have been used to calculate the amount of electron transfer from the ligand to the metal ion and to evaluate the Pd–N, Pd–O, and Pd–Cl coordination bonding interactions.

The 1,3-dipolar cycloaddition reaction is one of the most rapid, and efficient protocols to access, and construct highly divergent heterocycle chiral auxiliaries. Free catalyst synthesis of spirooxindole scaffold incorporating sulphone moiety via one pot&ndash, three component reaction of 6-chloro-isatin, L-proline, and the phenylvinylsulphone as dienophile is presented. The new regioisomer and diastereomer was isolated by precipitation without the tedious purification step, and then characterized via NMR and single crystal X-ray diffraction analysis. Using Hirshfeld analysis, the analysis of molecular packing was performed. It depended mainly on strong O&hellip, H and N&hellip, H interactions, and weak H&hellip, H, C&hellip, H, and Cl&hellip, H interactions as well. DFT calculations were used to optimize the experimental X-ray structure, which was found well matched with the calculated one. Reactivity descriptors based on the energies of the highest occupied (HOMO) and lowest unoccupied (LUMO) molecular orbitals were calculated. Additionally, the donor&ndash, acceptor interactions which stabilized the system via &sigma, &ndash, &sigma, *, &pi, &rarr, &pi, *, n&rarr, * and n&rarr, * electron delocalization processes were also computed using NBO calculations. The net interaction energies are 49.96, 235.38, 179.66 and 107.06 kJ/mol, respectively. Additionally, the calculated NMR chemical shifts correlated well with the experimental data (R2=0.99).

Here we report on the crystal structure of three enamine/imine TBA derivatives (1&minus, 3). Since the derivatives can take the form of enamine or imine tautomers, theoretical calculations were made to confirm that the former predominates due to higher stability (thermodynamic calculations). The enamines&rsquo, form was further corroborated by high activation energy (&Delta, G&ne, which is &gt, 60 kcal/mol in all the cases), thus requiring a large amount of energy to pass the barrier (kinetics calculations). Furthermore, 1&minus, 3 were found to show high static hyperpolarizability (&beta, tot), thereby making them potential candidates as nonlinear materials for electro-optical devices and crystal engineering.

The Mizoroki-Heck (MH) reaction involving aryl halides with various acrylates and acrylamides has been studied using air and moisture-stable imidazolium-based palladate pre-catalysts. These pre-catalysts can be converted into Pd-NHC species (NHC = N-heterocyclic carbene) under catalytic conditions and are capable of facilitating the Mizoroki-Heck reaction of aryl halides with various acrylates. The effects of solvent, catalyst loading, temperature and bases on the reaction outcome have been investigated. Various coupling partners were tolerated under the optimal reaction conditions catalyzed by palladate 1, [SIPr center dot H][Pd(eta(3)-2-Me-allyl)Cl-2]. The efficiency of the optimized synthetic methodology was tested on various aryl halides and substituted acrylates as well as acrylamides. The MH reaction yielded the coupled products in good to excellent isolated yields (up to 98%).

The discovery of metal-based complexes as potent urease inhibitor is a challenge. In this work, the new [CoL2]NO3 complex of the barbituric acid based ligand, 5-((benzylamino)methylene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione (HL) was synthesized. The structural features of the synthesized Co(III) complex were assigned using the single crystal X-ray diffraction techniques, Hirshfeld analysis, DFT calculations and other physicochemical techniques. Its structure comprised CoN4O2 coordination sphere with two ligands units (L¯) as mononegative tridentate NNO-donor ligand. The potency as urease inhibitor was evaluated in vitro. The [CoL2]NO3 complex (IC50 = 16.0 ± 0.54 µM) is better inhibitor than the drug acetohydroxamic acid as a reference (IC50 = 20.3 ± 0.43 µM). The docking studies of the [CoL2]NO3 was carried out using the active center of Jack Bean Urease (PDB 4GY7), and the resulting poses were analyzed visually to understand the interaction pattern.

Considerable attention has been focused on the [1,3] dipolar cycloaddition reaction approach of olefin with amino acid (sarcosine), and isatin which underwent smoothly, and afforded a highly functionalized complex molecule. The target spiroindolone analogue 4 was synthesized in excellent yield. The desired compound was elucidated based on X-ray single crystal diffraction technique. Compound 4 was examined against three different cancer cell lines for liver, breast and colorectal cancer (HepG2, MCF-7 and HCT-116, respectively). It showed high selectivity against colon cancer (HCT-116). Hirshfeld molecular packing analysis of 4 showed that the H⋯H, Cl⋯H and C⋯H contacts are the most abundant while the N⋯H and O⋯H hydrogen bonding interactions are the strongest. Molecular and electronic structures as well as the Uv–Vis and NMR spectra of 4 were discussed based on DFT calculations. The longest wavelength band observed at 298 nm was assigned for the HOMO-2/HOMO-1→LUMO excitations. The 1H and 13C NMR chemical shifts of 4 were calculated and compared with the experimental data (0.934–0.954).

Described herein is a one-pot protocol for the synthesis of a substituted spiropyrrolidine scaffold tethered benzo[b]thiophene analogue from (E)-3-(benzo[b]thiophen-2-yl)-1-(4-fluoro- phenyl)-prop-2-en-1-one. The described protocol has the advantage of the high purity of the cyclized adduct and high chemical yield. To assign the chemical structure, different spectrophotometric tools have been applied, including 1H-NMR, 13C-NMR, FTIR, and the X-ray single crystal technique. The X-ray structure showed that the studied compound exist in two disordered parts with equal partial occupancies. The energies of the two conformers were found to be very similar and not exceed 1 kcal/mol, which justifies their coexistence in the crystal with equal percentage. The molecular packing in the crystal was analyzed using Hirshfeld topology analysis. The packing described as two dimensional hydrogen bond network extended along the ac-plane in both conformers but the intermolecular interactions included in each conformer are not similar. The synthesized spiropyrrolidine scaffold tethered benzo[b]thiophene analogue was examined against cholinesterase inhibitory activity and show moderate activity compared to standard drug galantamine.

Ferrocene-based anti-inflammatory drug discovery has become an important area in medicinal chemistry. Utilizing the condensation of isatin or ferrocene carbaldehyde with nucleophile, such as oxamic acid hydrazide, the desired isatin 1, and ferrocene 2 oxamohydrazide derivatives were smoothly synthesized in high purity and yield. The structures of the isatin, and ferrocene oxamohydrazides were elucidated using single crystal X-ray diffraction technique, and DFT calculations. Hirshfeld analysis sheds the light on the importance of the O⋯H hydrogen bonds in the molecular packing in both compounds. The oxamohydrazides were examined for anti-inflammatory, and anti-leishmanial activities. The ferrocene oxamohydrazide analogue 2, (IC50 = 5.7 ± 0.3 μM) exhibited a potent anti-inflammatory effect, and was two times more active than the tested ibuprofen as control (IC50 = 11.2 ± 1.9 μM).

ADS thanks the Royal Society for a Wolfson Research Merit Award. We also thank the EPSRC UK National Mass Spectrometry Facility at Swansea University. SPN thanks King Abdullah University of Science and Technology (Award No. SR-2015-CCF-1974-03) and King Saud University for support. During an investigation into the potential union of Lewis basic isothiourea organocatalysis and gold catalysis, the formation of gold‐isothiourea complexes was observed. These novel gold complexes were formed in high yield and were found to be air‐ and moisture stable. A series of neutral and cationic chiral gold(I) and gold(III) complexes bearing enantiopure isothiourea ligands was therefore synthesized and fully characterized. The steric and electronic properties of the isothiourea ligands was assessed through calculation of their percent buried volume and the synthesis and analysis of novel iridium(I)‐isothiourea carbonyl complexes. The novel gold(I)‐ and gold(III)‐isothiourea complexes have been applied in preliminary catalytic and biological studies, and display promising preliminary levels of catalytic activity and potency towards cancerous cell lines and clinically‐relevant enzymes. Postprint

The designed compounds, 4a-p, were synthesized using a simple and smooth method with an asymmetric 1,3-dipolar reaction as the key step. The chemical structures for all synthesized compounds were elucidated and confirmed by spectral analysis. The molecular complexity and the absolute stereochemistry of 4b and 4e designed analogs were determined by X-ray crystallographic analysis. The anticancer activities of the synthesized compounds were tested against colon (HCT-116), prostate (PC-3), and hepatocellular (HepG-2) cancer cell lines. Molecular modeling revealed that the compound 4d binds through hydrophobic-hydrophobic interactions with the essential amino acids (LEU: 57, GLY: 58, ILE: 61, and HIS: 96) in the p53-binding cleft, as a standard p53-MDM2 inhibitor (6SJ). The mechanism underlying the anticancer activity of compound 4d was further evaluated, and the study showed that compound 4d inhibited colony formation, cell migration, arrested cancer cell growth at G2/M, and induced apoptosis through intrinsic and extrinsic pathways. Transactivation of p53 was confirmed by flow cytometry, where compound 4d increased the level of activated p53 and induced mRNA levels of cell cycle inhibitor, p21.

This report describes the evaluation of the biological activities of 13 gold-NHC complexes. These complexes were evaluated in vitro for their antioxidant properties, α-glucosidase, thymidine phosphorylase, β-glucuronidase and xanthine oxidase enzyme inhibition activities. Among the tested complexes, those bearing chloride ligands were found to be potent antioxidant, α-glucosidase, thymidine phosphorylase, β-glucuronidase and xanthine oxidase enzyme inhibitors, showing several hundred fold higher activity than the standard drugs. Some of these complexes were found to be potent antileishmanial agents, which were superior to standard antileishmanil drugs. These gold complexes were also evaluated for their in vitro cytotoxic activity against PC-3 (normal cells), HeLa (cervical cancer), MCF-3 (breast cancer) and 3T3 (mouse fibroblast) cell lines.

A series of barbiturates derivatives synthesized and screened for different set of bioassays are described. The molecular structures of compounds5a,5d,and5fwere solved by single-crystal X-ray diffraction techniques. The results of bioassay show that compounds4a,4b,4c,4d,4e,4f, and4gare potent antioxidants in comparison to the tested standards, butylated hydroxytoluene (BHT), andN-acetylcysteine. Compounds4a–4e(IC50=101.8±0.8–124.4±4.4 μM) and4g(IC50=104.1±1.9 μM) were more potent antioxidants than the standard (BHT,IC50=128.8±2.1 μM). The enzyme inhibition potential of these compounds was also evaluated,in vitro, against thymidine phosphorylase,α-glucosidase, andβ-glucuronidase enzymes. Compounds4c,4h,4o,4p,4q, 5f,and5mwere found to be potentα-glucosidase inhibitors and showed more activity than the standard drug acarbose, whereas compounds4v,and5hwere found to be potent thymidine phosphorylase inhibitors, more active than the standard drug, 7-deazaxanthine. All barbiturates derivatives (4a–4x,4z,and5a–5m) were found to be noncytotoxic against human prostate (PC-3), Henrietta Lacks cervical (HeLa) and Michigan Cancer Foundation-7 breast (MCF-7) cancer cell lines, and 3T3 normal fibroblast cell line, except4ywhich was cytotoxic against all the cell lines.

Trimolecular salt Michael adducts 2a–c were synthesized in excellent yields up to 92 % via one-pot multicomponent reactions in an aqueous medium. The chemical structures of compounds 2a–c were characterized by X-ray single-crystal diffraction techniques. Calculations of the density functional theory for the synthesized compound were performed. The stability of the products was deduced by TGA analysis. Compounds 2a–c were screened in vitro for different bio-assays such as thymidine phosphorylase inhibition assay, urease inhibition assay, β-glucuronidase inhibition assays and cytotoxicity against PC-3 and HeLa cell lines.

C13H11FN2O3, triclinic, P1̅, a = 5.7471(4) Å, b = 7.8734(6) Å, c = 13.3112(11) Å, α = 75.546(3)°, β = 78.183(3)°, γ = 77.540(3)°, V = 562.22(7) Å3, Z = 2, R gt (F) = 0.0444, wR ref (F 2) = 0.1234, T = 100 K.

C23H30FN5O6, monoclinic, P21/n (no. 14), a = 9.5772(3) Å, b = 15.9466(5) Å, c = 15.8380(5) Å, β = 103.951(1)°, V = 2347.49(13) Å3, Z = 4, R gt (F) = 0.0423, wR(F 2 ) = 0.192, T = 150 K.

C25H32Cl2F3N5O6, orthorhombic, P212121 (no. 19) a = 11.0768(4) Å, b = 15.6620(5) Å, c = 16.6830(5) Å, V = 2894.25(16) Å3, Z = 4, R gt(F) = 0.0509, wR(F 2) = 0.1498, T = 100 K.

Background Design and synthesis of pyrazole-dimedone derivatives were described by one-pot multicomponent reaction as new antimicrobial agents. These new molecular framework were synthesized in high yields with a broad substrate scope under benign conditions mediated by diethylamine (NHEt2). The molecular structures of the synthesized compounds were assigned based on different spectroscopic techniques (1H-NMR, 13C-NMR, IR, MS, and CHN). Results The synthesized compounds were evaluated for their antibacterial and antifungal activities against S. aureus ATCC 29213, E. faecalis ATCC29212, B. subtilis ATCC 10400, and C. albicans ATCC 2091 using agar Cup plate method. Compound 4b exhibited the best activity against B. subtilis and E. faecalis with MIC = 16 µg/L. Compounds 4e and 4l exhibited the best activity against S. aureus with MIC = 16 µg/L. Compound 4k exhibited the best activity against B. subtilis with MIC = 8 µg/L. Compounds 4o was the most active compounds against C. albicans with MIC = 4 µg/L. Conclusion In-silico predictions were utilized to investigate the structure activity relationship of all the newly synthesized antimicrobial compounds. In this regard, a ligand-based pharmacophore model was developed highlighting the key features required for general antimicrobial activity. While the molecular docking was carried out to predict the most probable inhibition and binding mechanisms of these antibacterial and antifungal agents using the MOE docking suite against few reported target proteins. Electronic supplementary material The online version of this article (10.1186/s13065-018-0399-0) contains supplementary material, which is available to authorized users.

Owing to their structural novelty and inherent three-dimensionality, spiro scaffolds have been shown indisputable promise as chemopreventive agents. A new series of heterocycles containing spirooxindole and pyrrolidine rings were synthesized by the 1,3-dipolar cycloaddition of an azomethine ylide, which was generated in situ by the condensation of a secondary amino acid ( l ‑proline) and dicarbonyl compounds (isatin), with dipolarophiles. This method is simple and provides diverse and biologically interesting products. The new series of compounds with a high degree of stereo- and regioselectivity were evaluated against breast cancer cell lines (MCF-7) and leukemia (K562). Among them, compound 4g was identified as the most potent with IC50 values of 15.49 ± 0.04 μM, against breast cancer cell lines (MCF-7) compared to standard drug 5-Fu (IC50 = 78.28 ± 0.2 μM) and compound 4i IC50 values of 13.38 ± 0.14 μM against leukemia (K562) compared to standard drug 5-fluorouracil (5-FU) (IC50 = 38.58 ± 0.02). The selective apoptotic effects of 4g were investigated against MCF-12 normal mammary cell and the cytotoxicity of 4g was not associated with any induction of necrosis compared to untreated cells. Molecular docking studies were investigated. From the docking data, these compounds could be act as small molecules that inhibit the MDM2-p53 interaction.

Synthesis, structure, and evaluation of in vitro α-glucosidase enzyme inhibition of a new class of diethylammonium salts of aryl substituted thiobarbituric acid is described. This protocol is straight, environmentally benign and efficient, involving Aldol-Michael addition reaction in one pot fashion. The 3D chemical structures of the synthesized compounds were assigned based on spectroscopic methods and X-ray single crystal diffraction analyses. All synthesized compounds 3a-3n were evaluated for their in vitro α-glucosidase enzyme inhibitory activity, whereas acarbose was used as the standard drug (IC50=840±1.73µM). All tested compounds were found to possess varying degree of α-glucosidase enzyme inhibition activity with (IC50=19.46±1.84-415.8±4.0µM). Compound3i(IC50=19.4±1.84µM) exhibited the highest activity. To the best of knowledge this is the first report of the in vitro α-glucosidase enzyme inhibition by the diethylamonium salts of aryl substituted thiobarbituric acid. Furthermore, molecular docking studies of selected compounds were also performed to see interactions between active compounds and binding sites.

Four chalcone structures based on cyclohexanone cores were presented. The structures of bis-benzylidenecyclohexanone analogs 3a-d were elucidated using spectrophotometric and single-crystal X-ray techniques. Compounds 3a, 3b, and 3d crystalized in the monoclinic crystal system with the space group P21/c. However, 3c crystalized in the orthorhombic system with the space group Pna21. A set of computational studies related to the structures were carried out. Using the B3LYP method and the 6-31G(d,p) basis set, the molecular structures of the studied dienones were optimized, followed by the evaluation of their electronic properties and UV–vis spectra. The bond distances and angles well-correlated with the experimental data. All the dienones were stabilized by C–H⋯O intramolecular H-bonding interactions. The presence of two Cl atoms at the ortho-position of each phenyl ring in 3c caused steric hinderance with the cyclohexanone ring, leading to the weakest H⋯O interactions among the studied compounds. The TD-DFT method was used to assign and explain the origin of the electronic spectra of the studied dienones.

The crystal structures of five new chalcones derived from N-ethyl-3-acetylindole with different substituents were investigated: (E)-3-(4-bromophenyl)-1-(1-ethyl-1H-indol-3-yl)prop-2-en-1-one (3a), (E)-3-(3-bromophenyl)-1-(1-ethyl-1H-indol-3-yl)prop-2-en-1-one (3b), (E)-1-(1-ethyl-1H-indol-3-yl)-3-(4-methoxyphenyl)prop-2-en-1-one (3c), (E)-1-(1-ethyl-1H-indol-3-yl)-3-mesitylprop-2-en-1-one (3d), and (E)-1-(1-ethyl-1H-indol-3-yl)-3-(furan-2-yl)prop-2-en-1-one (3e). The molecular packing of the studied compounds is controlled mainly by C&ndash, H&sdot, &sdot, O hydrogen bonds, C&ndash, &pi, interactions, and &pi, &middot, stacking interactions, which were quantitatively analyzed using Hirshfeld topology analysis. Using density functional theory (DFT) calculations, the order of polarity (3b ˂ 3d ˂ 3e ˂ 3a ˂ 3c) was determined. Several chemical reactivity indices such as the ionization potential (I), electron affinity (A), chemical potential (&mu, ), hardness (&eta, ), electrophilicity (&omega, ) and nucleophilicity (N) indices were calculated, and these properties are discussed and compared. In addition, the antiproliferative activity of the five new chalcones was studied.

A one-pot reaction was described that results in various pyrazole-thiobarbituric acid derivatives as new pharmacophore agents. These new heterocycles were synthesized in high yields with a broad substrate scope under mild reaction conditions in water mediated by NHEt2. The molecular structures of the synthesized compounds were assigned based on different spectroscopic techniques. The new compounds were evaluated for their antibacterial and antifungal activity. Compounds 4h and 4l were the most active compounds against C. albicans with MIC = 4 µg/L. Compound 4c exhibited the best activity against S. aureus and E. faecalis with MIC = 16 µg/L. However, compounds 4l and 4o were the most active against B. subtilis with MIC = 16 µg/L. Molecular docking studies for the final compounds and standard drugs were performed using the OpenEye program.