Exploring Antimicrobial Features for New Imidazo[4,5-b]pyridine Derivatives Based on Experimental and Theoretical Study.

5-bromopyridine-2,3-diamine reacted with benzaldehyde to afford the corresponding 6-Bromo-2-phenyl-3H-imidazo[4,5-b]pyridine (1). The reaction of the latter compound (1) with a series of halogenated derivatives under conditions of phase transfer catalysis solid-liquid (CTP) allows the isolation of the expected regioisomers compounds (2-8). The alkylation reaction of (1) gives, each time, two regioisomers, N3 and N4; in the case of ethyl bromoactate, the reaction gives, at the same time, the three N1, N3 and N4 regioisomers. The structures of synthesized compounds were elucidated on the basis of different spectral data (1H NMR, 13C NMR), X-Ray diffraction and theoretical study using the DFT method, and confirmed for each compound. Hirshfeld surface analysis was used to determine the intermolecular interactions responsible for the stabilization of the molecule. Density functional theory was used to optimize the compounds, and the HOMO-LUMO energy gap was calculated, which was used to examine the inter/intra molecular charge transfer. The molecular electrostatic potential map was calculated to investigate the reactive sites that were present in the molecule. In order to determine the potential mode of interactions with DHFR active sites, the three N1, N3 and N4 regioisomers were further subjected to molecular docking study. The results confirmed that these analogs adopted numerous important interactions, with the amino acid of the enzyme being targeted. Thus, the most docking efficient molecules, 2 and 4, were tested in vitro for their antibacterial activity against Gram-positive bacteria (Bacillus cereus) and Gram-negative bacteria (Escherichia coli). Gram-positive bacteria were more sensitive to the action of these compounds compared to the Gram-negative, which were much more resistant.

Characterizations of Six Pomegranate (Punica granatum L.) Varieties of Global Commercial Interest in Morocco: Pomological, Organoleptic, Chemical and Biochemical Studies.

Pomegranate variety properties are important not only to demonstrate their diversity but also to satisfy the current market need for high-quality fruits. This study aims to characterize pomological and physico-chemical features as well as the antioxidant capacity of Moroccan local cultivars (Djeibi, Mersi, Sefri 1 and Sefri 2) compared to the imported ones (Mollar de Elche and Hicaz). The pomological characteristics of varieties were relatively diverse. The juice varieties (PJ) displayed a marketed variability in organoleptic and quality properties, such as the flavor, juice yield, and micro/macronutrients contents. Interrelationships among the analyzed properties and PJ varieties were investigated by principal component analysis (PCA). Dimension of the data set was reduced to two components by PCA accounting for 64.53% of the variability observed. The rinds varieties (PR) were studied for their total phenolics, flavonoids, and condensed tannins quantifications. PR varieties extracts exhibited different levels of free radical scavenging activity and local varieties revealed a greater potential with stability over time. The HPLC-DAD analyses of PR extracts revealed (+) catechin as the major compound, where the highest content was found for the local varieties. The SEC analysis showed the molecular weight distribution of phenolic compounds with a high size of condensed tannins formed by the polymerization of the catechin monomer. Given these properties, this research provides an easy selection of high-quality fruits as potential candidates for local market needs.

Antiproliferative and apoptotic activity of new indazole derivatives as potential anticancer agents.

To develop potent and selective anticancer agents, a series of novel polysubstituted indazoles was synthesized and evaluated for their in vitro antiproliferative and apoptotic activities against two selected human cancer cell lines (A2780 and A549). Several compounds showed an interesting antiproliferative activity, with IC50 values ranging from 0.64 to 17 µM against both cell lines. The most active indazoles were then tested in different pharmacological dilution conditions, adding five new cell lines (A2780, A549, IMR32, MDA-MB-231, and T47D) as targets, confirming their antiproliferative activity. Furthermore, selected compounds were able to trigger apoptosis to a significant extent and to cause, in part, a block of cells in the S phase of the cell cycle, with a concomitant decrease of cells in the G2/M and/or G0/G1 phases and the generation of hypodiploid peaks. However, molecule 7d caused a great increase of cells in G2/M and the appearance of polyploid cells. Altogether, our results suggest a good pharmacological activity for our selected polysubstituted indazoles, which are suggestive of a preferential mechanism of action as cell cycle-specific antimetabolites or as an inhibitor of enzyme activities involved in DNA synthesis, except for 7d, which, on the contrary, seems to have a mechanism involving the microtubule system.

Improvement of Heliciculture by Three Medicinal Plants Belonging to the Lamiaceae Family.

Snails were fed with three medicinal plants belonging to the Lamiaceae family (rosemary, sage, and peppermint) in order to test their effects on those animals with high nutritive values. The media of raising were flour containing different percentages of the cited plants ranging from 1% to 9%. The feed had benefits on the raised snails depending on the plant and its percentage. Minerals in those aromatic plants, especially zinc and magnesium, had their effect on protein synthesis in snails fed with those plant percentages. Rosemary was the most profitable plant with the highest protein amount, the lowest mortality rate, and reduced microbial charge. Furthermore, it was a good regulator of the specific catalase activity which confirmed the role of the antioxidant activity of rosemary during raising snails.

1-[(1-Benzyl-1H-1,2,3-triazol-4-yl)meth-yl]indoline-2,3-dione.

In the title compound, C18H14N4O2, the triazole ring makes dihedral angles of 77.32 (8) and 75.56 (9)°, respectively, with the indoline residue and the terminal phenyl group. In the crystal, mol-ecules are linked by C-H⋯N hydrogen bonds into tapes parallel to the b axis. The tapes are linked together by π-π inter-actions between triazole rings [inter--centroid distance = 3.4945 (9) Å].

3-(2,3-Dioxoindolin-1-yl)propane-nitrile.

The asymmetric unit of the title compound, C11H8N2O2, contains two independent mol-ecules (A and B). Each mol-ecule is build up from fused five- and six-membered rings with the former linked to a cyano-ethyl group. The indoline ring and two carbonyl O atoms of each mol-ecule are nearly coplanar, with the largest deviations from the mean planes being 0.0198 (9) (mol-ecule A) and 0.0902 (9) Š(mol-ecule B), each by a carbonyl O atom. The fused ring system is nearly perpendicular to the mean plane passing through the cyano-ethyl chains, as indicated by the dihedral angles between them of 69.72 (9) (mol-ecule A) and 69.15 (9)° (mol-ecule B). In the crystal, mol-ecules are linked by C-H⋯O and π-π [inter-centroid distance between inversion-related indoline (A) rings = 3.6804 (7) Å] inter-actions into a double layer that stacks along the a-axis direction.

Crystal structure, Hirshfeld surface analysis, crystal voids, inter-action energy calculations and energy frameworks, and DFT calculations of 1-(4-methyl-benz-yl)in-do-line-2,3-dione.

The in-do-line portion of the title mol-ecule, C16H13NO2, is planar. In the crystal, a layer structure is generated by C-H⋯O hydrogen bonds and C-H⋯π(ring), π-stacking and C=O⋯π(ring) inter-actions. The Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H⋯H (43.0%), H⋯C/C⋯H (25.0%) and H⋯O/O⋯H (22.8%) inter-actions. Hydrogen bonding and van der Waals inter-actions are the dominant inter-actions in the crystal packing. The volume of the crystal voids and the percentage of free space were calculated to be 120.52 Å3 and 9.64%, respectively, showing that there is no large cavity in the crystal packing. Evaluation of the electrostatic, dispersion and total energy frameworks indicate that the stabilization is dominated by the dispersion energy contributions in the title compound. Moreover, the DFT-optimized structure at the B3LYP/6-311G(d,p) level is compared with the experimentally determined mol-ecular structure in the solid state.

Crystal structure, Hirshfeld surface analysis, calculations of crystal voids, inter-action energy and energy frameworks as well as density functional theory (DFT) calculations of 3-[2-(morpholin-4-yl)eth-yl]-5,5-di-phenyl-imidazolidine-2,4-dione.

In the title mol-ecule, C21H23N3O3, the imidazolidine ring slightly deviates from planarity and the morpholine ring exhibits the chair conformation. In the crystal, N-H⋯O and C-H⋯O hydrogen bonds form helical chains of mol-ecules extending parallel to the c axis that are connected by C-H⋯π(ring) inter-actions. A Hirshfeld surface analysis reveals that the most important contributions for the crystal packing are from H⋯H (55.2%), H⋯C/C⋯H (22.6%) and H⋯O/O⋯H (20.5%) inter-actions. The volume of the crystal voids and the percentage of free space were calculated to be 236.78 Å3 and 12.71%, respectively. Evaluation of the electrostatic, dispersion and total energy frameworks indicates that the stabilization is dominated by the nearly equal electrostatic and dispersion energy contributions. The DFT-optimized mol-ecular structure at the B3LYP/6-311 G(d,p) level is compared with the experimentally determined mol-ecular structure in the solid state. Moreover, the HOMO-LUMO behaviour was elucidated to determine the energy gap.

Sustainable Collagen Film Preparation with Tannins Extracted from Moroccan Pomegranate Byproduct Varieties: Thermal, Structural, and Nanoscaled Studies.

Recently, obtaining collagen films using a cross-linking technique has been a successful strategy. The current investigation used six cross-linker extracts (CE) from six different pomegranate varieties' byproducts to make and characterize collagen-tannin films using acid-soluble collagen (SC). The polymeric film has a yellow hue after CE incorporation. Fourier transform infrared spectroscopy assessed the impact of CE and its successful interaction within the matrix. The shifts verify different interactions between extracts and collagen functional groups, where they likely form new hydrogen bonds, retaining their helix structure without damaging the matrix. Scanning electron microscopy was used to analyze the morphology and fiber size. The average diameter of the fibers was found to be about 3.64 µm. Thermal behaviors (denaturation and degradation) were investigated by thermogravimetric analysis. The weight losses of cross-linked films increased by around 20% compared to non-cross-linked ones. This phenomenon was explained by the absence of telopeptide sections in the collagen helical structure, typically reinforced by lysine and hydroxylysine covalent linkages. Nanoscaled observations were also accomplished using transmission electron microscopy (TEM) on SC and SC-CE. The TEM analysis confirmed the CE polymerization degree effect on the cross-linking density via the overlap sequences, ranging up to 32.38 ± 2.37 nm on the fibril. The prepared biodegradable collagen-tannin film showed higher cross-linking density, which is expected to improve the biomaterial applications of collagen films while exploiting the underrated pomegranate byproducts.

3-Benzyl-1-{[3-(4-chloro-phen-yl)isoxazol-5-yl]meth-yl}-1H-benzimidazol-2(3H)-one.

In the title compound, C24H18ClN3O2, the benzimidazole plane is nearly perpendicular to the phenyl ring and to the isoxazole ring, making dihedral angles of 75.95 (7) and 73.04 (8)°, respectively, but the two residues point in opposite directions with respect to the benzimidazole plane. The dihedral angle between the chloro-phenyl and isoxazole rings is 7.95 (8)°. In the crystal, mol-ecules are linked by pairs of C-H⋯O hydrogen bonds into inversion dimers.

1-(Prop-2-yn-yl)-1H-benzimidazol-2(3H)-one.

The benzimidazolone part of the title mol-ecule, C10H8N2O, is almost planar [r.m.s. deviation = 0.014 (1) Å] and the NCH2C CH group forms a dihedral angle of 67.95 (6)° with its best plane. In the crystal, mol-ecules form inversion dimers via pairs of N-H⋯O hydrogen bonds. C-H⋯O inter-actions connect the dimers, forming a two-dimensional polymeric network parallel to (100).

1-(4-Methyl-benz-yl)-1H-benzimidazol-2(3H)-one.

In the title compound, C15H14N2O, the fused five- and six-membered ring system is essentially planar, the maximum deviation from the mean plane being 0.009 (1) Å. The benzimidazol-2(3H)-one residue is nearly perpendicular to the benzyl ring, forming a dihedral angle of 77.41 (6)°. In the crystal, inversion dimers are formed by pairs of N-H⋯O hydrogen bonds; these dimers are linked by weak C-H⋯O inter-actions into a two-dimensional array in the (102) plane.

1-Allyl-5-nitro-1H-benzimidazol-2(3H)-one.

The benzimidazolone residue in the title mol-ecule, C10H9N3O3, is almost planar, with the largest deviation from the mean plane being 0.016 (2) Šfor the C atom linked to the nitro group. This plane is nearly perpendicular to the 1-allyl chain as indicated by the C-N-C-C torsion angle of 90.9 (3)°. The fused-ring system makes a dihedral angle of 5.6 (3)° with the nitro group, leading to a synperiplanar conformation. In the crystal, zigzag supra-molecular chains are formed along the a axis by N-H⋯O hydrogen bonds.

3-Benzyl-6-bromo-1H-imidazo[4,5-b]pyridin-2(3H)-one.

The fused imidazole and pyridine rings in the title compound, C13H10BrN3O, are linked to a benzyl group. The fused ring system is essentially planar, the largest deviation from the mean plane being 0.006 (2) Å. The phenyl ring is not coplanar with the fused ring system, as indicated by the dihedral angle of 67.04 (12)°. In the crystal, mol-ecules are linked by pairs of N-H⋯O hydrogen bonds, forming inversion dimers.

Ethyl 2-oxo-3-(3-phthalimidoprop-yl)-2,3-dihydro-1H-1,3-benzimidazole-1-carboxyl-ate.

In the title compound, C21H19N3O5, the phthalimide and benzamidazole ring systems are linked by a propyl chain. The benzamidazole unit also carries an eth-oxy-carbonyl substit-uent. The phthalimido and benzimidazole ring systems are essentially planar, the maximum deviations from their mean planes being 0.008 (2) and 0.020 (2) Å, respectively. The two ring systems are almost orthogonal to one another, making a dihedral angle of 82.37 (8)°. In the crystal, C-H⋯O hydrogen bonds and C-H⋯π contacts stack the mol-ecules along the b axis.

1-Allyl-3-benzyl-1H-benzimidazol-2(3H)-one.

In the title compound, C17H16N2O, the fused benzimidazol-2(3H)-one system is essentially planar, the largest deviation from the mean plane being 0.006 (2) Šfor the carbonyl C atom. Its mean plane is almost perpendicular to the benzyl plane and to the allyl group, making dihedral angles of 80.6 (1) and 77.4 (3)°, respectively. The benzyl group and the allyl subsituent lie on opposite sides of the fused ring system. In the crystal, mol-ecules are linked by bifurcated C-H⋯O hydrogen bonds in which the carbonyl O atom acts as accepter to two aromatic C-H groups, forming a two-dimensional network parallel to (001).

1-Octylindoline-2,3-dione.

In the title compound, C16H21NO2, the indoline ring and the two ketone O atoms are approximately coplanar, the largest deviation from the mean plane being 0.063 (2) Å. The mean plane through the fused ring system is nearly perpendicular to the mean plane passing through the 1-octyl chain [dihedral angle = 77.53 (17)°]. In the crystal, mol-ecules are linked by C-H⋯O hydrogen bonds, forming a three-dimensional network.

6-Bromo-1,3-bis-[(1,3-dioxolan-2-yl)meth-yl]-1H-imidazo[4,5-b]pyridin-2(3H)-one.

In the title compound, C14H16BrN3O5, the N atoms adjacent to the carbonyl group in the five-membered ring are substituted by (1,3-dioxolan-2-yl)methyl groups. The fused ring system is essentially planar, with the largest deviation from the mean plane being 0.014 (2) Šfor the C atom bearing the Br atom. The first oxolane ring, attached on the side of the N atom belonging to the pyridine ring, has an envelope conformation with one of the O atoms as the flap, whereas the second oxolane ring displays a twisted boat conformation. The two oxolane rings display envelope and twisted boat conformations. In the crystal, mol-ecules are linked by C-H⋯O hydrogen bonds, building chains parallel to the a-axis direction.

5-Nitro-1,3-bis-(prop-2-yn-yl)-1H-1,3-benzimidazol-2(3H)-one.

The title compound, C13H9N3O3, crystallizes with two identical but differently oriented mol-ecules in the asymmetric unit, the dihedral angle between the fused-ring systems of the two molecules being 64.39 (7)°. The two prop-2-ynyl chains are located on opposite sides of the mol-ecule and are nearly perpendicular to the fused ring plane, as indicated by the C-N-C-C torsion angles in the range 106.0 (3)-113.4 (3)°. In the crystal, the two mol-ecules are linked through C-H⋯O hydrogen bonds into dimers, which are subsequently linked by further C-H⋯O inter-actions, building a three-dimensional network.

Synthesis, crystal structure and Hirshfeld surface analysis of 1-(12-bromo-dodec-yl)indoline-2,3-dione.

In the title compound, C20H28BrNO2, the indoline portion is almost planar and the 12-bromo-dodecyl chain adopts an all-trans conformation apart from the gauche terminal C-C-C-Br fragment. A micellar-like structure is generated in the crystal by C-H⋯O hydrogen bonds and π-stacking inter-actions between indolinedione head groups and inter-calation of the 12-bromo-dodecyl tails. The Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H⋯H (58.9%), H⋯O/O⋯H (17.9%) and H⋯Br/Br⋯H (9.5%) contacts. A density functional theory (DFT) optimized structure at the B3LYP/ 6-311 G(d,p) level shows good agreement with the experimentally determined mol-ecular structure in the solid state.