Crystal structure determination and analyses of Hirshfeld surface, crystal voids, inter-molecular inter-action energies and energy frameworks of 1-benzyl-4-(methyl-sulfan-yl)-3a,7a-di-hydro-1H-pyrazolo-[3,4-d]pyrimidine.

The pyrazolo-pyrimidine moiety in the title mol-ecule, C13H12N4S, is planar with the methyl-sulfanyl substituent lying essentially in the same plane. The benzyl group is rotated well out of this plane by 73.64 (6)°, giving the mol-ecule an approximate L shape. In the crystal, C-H⋯π(ring) inter-actions and C-H⋯S hydrogen bonds form tubes extending along the a axis. Furthermore, there are π-π inter-actions between parallel phenyl rings with centroid-to-centroid distances of 3.8418 (12) Å. A Hirshfeld surface analysis of the crystal structure indicates that the most important contributions to the crystal packing are from H⋯H (47.0%), H⋯N/N⋯H (17.6%) and H⋯C/C⋯H (17.0%) inter-actions. The volume of the crystal voids and the percentage of free space were calculated to be 76.45 Å3 and 6.39%, showing that there is no large cavity in the crystal packing. Evaluation of the electrostatic, dispersion and total energy frameworks indicate that the cohesion of the crystal structure is dominated by the dispersion energy contributions.

Design and evaluation of novel inhibitors for the treatment of clear cell renal cell carcinoma.

The efficacy of conventional chemotherapies in treating clear cell renal cell carcinoma (ccRCC) is often limited due to its high molecular diversity, generally low response rates to standard treatments, and prevalent drug resistance. Recent advancements in the molecular understanding of ccRCC, alongside the discovery of novel therapeutic agents targeting specific proteins, have significantly altered the treatment landscape for ccRCC. Here, we synthesized 27 new compounds that are derivatives of TG-101209 to modulate BUB1B (BUB1 mitotic checkpoint serine/threonine kinase B). BUB1B has been recently identified as a drug target for the development of effective ccRCC treatment based on global transcriptomics profiling of ccRCC tumours and gene co-expression network analysis. We characterized the molecular structures of these 27 compounds by 1H and 13C NMR and Mass spectrometry. We evaluated the effect of these 27 compounds by analysing the modulation of the BUB1B expression. Our primary objective was to design and assess the efficacy of these new compounds in reducing the viability of Caki-1 cells, a ccRCC cell line. We performed the computational docking studies by the Schrödinger Maestro software and demonstrated that three of these compounds (13a, 5i, and 5j) effectively downregulated BUB1B expression and eventually triggered necrosis and apoptosis in the Caki-1 cell line based on the structure-activity relationship (SAR) analysis. The IC50 values for compounds 13a, 5i, and 5j were calculated as 2.047 µM, 10.046 µM, and 6.985 µM, respectively, indicating their potent inhibitory effects on cell viability. Our study suggests that these compounds targeting BUB1B could offer a more effective and promising approach for ccRCC treatment compared to the conventionally used tyrosine kinase inhibitors. Our study underscores the potential of leveraging targeted therapies against specific molecular pathways in ccRCC may open new avenues for the development of effective treatment strategies against ccRCC.

Synthesis, crystal structure, DFT, Hirshfeld surface analysis, energy frameworks and in-Silico drug-targeting PFKFB3 kinase of novel triazolequinoxalin derivative (TZQ) as a therapeutic Strategy against cancer.

Overall, drug design is a dynamic and evolving field, with researchers constantly working to improve their understanding of molecular interactions, develop new computational methods, and explore innovative techniques for creating effective and safe medications. The process can involve steps such as the identification of targets, the discovery of lead compounds, lead optimization, preliminary testing, human trials, regulatory approval and finally post-marketing surveillance, all aimed at bringing a new drug from concept to market. In this article, the synthesis of the novel triazolequinoxalin (TZQ) 1-((1-hexyl-1H-1,2,3-triazol-5-yl)methyl)-3-phenylquinoxalin-2(1H)-one (4) is reported. The structure has been identified with a variety of spectroscopic methods (1H, 13C NMR, and LC-MS) and finally, the structure has been determined by X-ray diffraction (XRD) studies. The TZQ molecule has crystallized in the monoclinic space C2/c group with unit cell dimensions a = 41.201(2) Å, b = 10.6339(6) Å, c = 9.4997(4) Å, ß = 93.904(4). The crystal structure is stabilized by intermolecular interactions (N-H ⋯ O and N-H … Cg) occurring within the molecule. The presence of these intermolecular interactions is evaluated through analysis of Hirshfeld surfaces (HS) and two-dimensional (2D) chemical fingerprints map. Additionally, energy frameworks were employed to identify the prevailing interaction energy influencing the molecular arrangement. Density Functional Theory (DFT) calculations were computed to establish concurrence between theoretical and experimental results. Furthermore, the HOMO-LUMO energy levels were determined using the B3LYP/6-31+G(d, p) level of theory. Finally, molecular docking was used to predict the anti-cancer activity of the compound (4) against PFKFB3 kinase and presented noticeable hydrophilic and hydrophobic interactions at the active site region.

Diethyl 2,2'-[({2-chloro-5-[(2-eth-oxy-2-oxoeth-yl)(2-methyl-indolin-1-yl)carbamo-yl]phen-yl}sulfon-yl)aza-nedi-yl]di-acetate.

The majority of the title mol-ecule, C28H34ClN3O9S, is disordered over two closely spaced sets of sites; the site occupancy of the major component = 0.542 (3). The conformation of each component is approximately U-shaped with the chloro-benzene ring forming the base and the indolinyl and sulfamoyl groups the sides; an intra-molecular C-H⋯Cl hydrogen bond possibly contributes to the stabilization of the conformation. In the crystal, a corrugated layer structure parallel to the ab plane is formed by C-H⋯O and C-H⋯Cl hydrogen bonds together with C-H⋯π(ring) inter-actions.

Synthesis, structural characterization, antioxidant and antidiabetic activities, DFT calculation, and molecular docking of novel substituted phenolic and heterocyclic compounds.

The current work describes the preparation of three unexpected compounds: a tetrasubstituted phenolic compound, an isocoumarin, and a pyranopyridine, bearing various substituent groups obtained through the condensation of 6-methyl-4-hydroxypyran-2-one 1 with 2-aminopyridine 2 under mild conditions. Plausible mechanisms explaining the formation of these compounds have been presented. Their structures have been elucidated using spectral data and confirmed by crystallographic studies. Furthermore, optimized geometries of and electronic distribution of FMOs orbitals are investigated in the PCM solvent model at the B3LYP/6-311++G(d,p) level of theory. The compounds were tested for their antioxidant and antidiabetic activities. Moreover, the binding interactions between the compounds and α-glucosidase and α-amylase were determined through their docking into the binding sites of the target enzymes using the Autodock package.Communicated by Ramaswamy H. Sarma.

Crystal structure, Hirshfeld surface analysis and inter-action energy calculation of 4-(furan-2-yl)-2-(6-methyl-2,4-dioxo-pyran-3-yl-idene)-2,3,4,5-tetra-hydro-1H-1,5-benzodiazepine.

The title compound {systematic name: (S,E)-3-[4-(furan-2-yl)-2,3,4,5-tetra-hydro-1H-benzo[b][1,4]diazepin-2-yl-idene]-6-methyl-2H-pyran-2,4(3H)-dione}, C19H16N2O4, is constructed from a benzodiazepine ring system linked to furan and pendant di-hydro-pyran rings, where the benzene and furan rings are oriented at a dihedral angle of 48.7 (2)°. The pyran ring is modestly non-planar [largest deviation of 0.029 (4) Šfrom the least-squares plane] while the tetra-hydro-diazepine ring adopts a boat conformation. The rotational orientation of the pendant di-hydro-pyran ring is partially determined by an intra-molecular N-HDiazp⋯ODhydp (Diazp = diazepine and Dhydp = di-hydro-pyran) hydrogen bond. In the crystal, layers of mol-ecules parallel to the bc plane are formed by N-HDiazp⋯ODhydp hydrogen bonds and slipped π-π stacking inter-actions. The layers are connected by additional slipped π-π stacking inter-actions. A Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H⋯H (46.8%), H⋯O/O⋯H (23.5%) and H⋯C/C⋯H (15.8%) inter-actions, indicating that van der Waals inter-actions are the dominant forces in the crystal packing. Computational chemistry indicates that in the crystal the N-H⋯O hydrogen-bond energy is 57.5 kJ mol-1.

Solvent induced supramolecular polymorphism in Cu(II) coordination complex built from 1,2,4-triazolo[1,5-a]pyrimidine: Crystal structures and anti-oxidant activity.

Two Cu(II) coordination complexes, C1 and C2 of the formula [Cu(4)2(H2O)2], have been prepared by reaction between CuCl2·2H2O and 7-ethoxycarbonylmethyl-5-methyl-1,2,4[1,5-a]pyrimidine (L) in a 1:2 M:L molar ratio. The L molecule decomposes during the reaction process into 7-carboxy-5-methyl-[1,2,4]-triazolo[1,5-a]pyrimidine (4) through an intermediate, ethyl 2,2-dihydroxy-2-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)acetate (5), which has been isolated and its crystal structure determined by X-ray diffraction. The X-ray analysis of the single crystals of [Cu(4)2(H2O)2] obtained from the slow evaporation of EtOH and MeOH, separately, revealed the formation of "solvent induced" polymorphs C1 and C2, respectively. The primary supramolecular synthon for C1 and C2 are six membered ring, and square shaped hydrogen bonded architecture, respectively. The self-assembly of such synthons resulted in a two dimensional hydrogen bonded sheet supported by OH⋯O interactions. In addition, the antioxidant properties of the ligands and its complexes were evaluated in vitro using 1,1-diphenyl-2-picrylhydrazyl acid, 2,2'-azino-bis (3-ethylbenzothiazoline-6 sulfonic acid radical scavenging methods and ferric reducing antioxidant power.

Crystal structure and Hirshfeld surface analysis of N-(tert-but-yl)-2-(phenyl-ethyn-yl)imidazo[1,2-a]pyridin-3-amine.

The bicyclic imidazo[1,2-a]pyridine core of the title compound, C19H19N3, is relatively planar with an r.m.s. deviation of 0.040 Å. The phenyl ring is inclined to the mean plane of the imidazo[1,2-a]pyridine unit by 18.2 (1)°. In the crystal, mol-ecules are linked by N-H⋯H hydrogen bonds, forming chains along the c-axis direction. The chains are linked by C-H⋯π inter-actions, forming slabs parallel to the ac plane. The Hirshfeld surface analysis and fingerprint plots reveal that the crystal structure is dominated by H⋯H (54%) and C⋯H/H⋯C (35.6%) contacts. The crystal studied was refined as an inversion twin.

Crystal structure and Hirshfeld surface analysis of 3-(4-meth-oxy-phen-yl)-1-methyl-4-phenyl-1H-pyrazolo-[3,4-d]pyrimidine.

In the title mol-ecule, C19H16N4O, the planar pyrazolo-pyrimidine moiety is inclined to the attached phenyl rings by 35.42 (4) and 54.51 (6)°. In the crystal, adjacent mol-ecules are linked into chains parallel to [110] and [10] by C-H⋯O and C-H⋯N hydrogen bonds. Additional C-H⋯π(ring) inter-actions lead to the formation of the final three-dimensional network structure. The Hirshfeld surface analysis of the title compound suggests that the most significant contributions to the crystal packing are from H⋯H (48.2%), C⋯H/H⋯C (23.9%) and N⋯H/H⋯N (17.4%) contacts.

Crystal structure and Hirshfeld surface analysis of 5-[(5-nitro-1H-indazol-1-yl)meth-yl]-3-phenyl-4,5-di-hydro-isoxazole.

In the title compound, C17H14N4O3, the indazole unit is planar to within 0.0171 (10) Šand makes dihedral angles of 6.50 (6) and 6.79 (4)°, respectively, with the nitro and pendant phenyl groups. The conformation of the oxazole ring is best described as an envelope. In the crystal, oblique stacks along the a-axis direction are formed by π-π stacking inter-actions between the indazole unit and the pendant phenyl rings of adjacent mol-ecules. The stacks are linked into pairs through C-H⋯O hydrogen bonds. Hirshfeld surface analysis and two-dimensional fingerprint plots indicate that the most important contributions to the crystal packing are from H⋯H (36.3%), O⋯H/H⋯O (23.4%), C⋯H/H⋯C (13.4%) and N⋯H/H⋯N (11.4%) inter-actions.

Crystal structure and Hirshfeld surface analysis of 1-benzyl-3-(prop-2-yn-1-yl)-2,3-di-hydro-1H-1,3-benzo-diazol-2-one.

The title compound, C17H14N2O, is built up from the planar benzo-diazole unit linked to the benzyl and propynyl substituents. The substituents are rotated significantly out of the benzo-diazole plane, where the benzyl group is inclined by 68.91 (7)° to the benzo-diazole unit. In the crystal, the mol-ecules are linked via inter-molecular C-HBnzdzl⋯O and C-HBnzy⋯O (Bnzdzl = benzo-diazole and Bnzy = benz-yl) hydrogen bonds, enclosing R 4 4(27) ring motifs, into a network consisting of rectangular layers parallel to the bc plane which are also stacked along the a-axis direction being associated through C-H⋯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 (43.6%), H⋯C/C⋯H (42.0%) and H⋯O/O⋯H (8.9%) inter-actions.