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· New EBF derivatives with acylamino linker were synthesized and their activities were tested. · EBF derivatives with an acylamino linker showed higher aphicidal activities. · The hydrophobic force was essential for high target protein binding activity. · The scaffold structure of EBF was essential to maintain their bioactivity. Insect odorant-binding proteins (OBPs) have significant roles in the transmission of semiochemical signals. In our previous study, a series of salicylate-substituted carboxyl (E)-β-farnesene (EBF) derivatives were synthesized with a carboxyl linker to bridge the EBF geranyl chain with salicylate aromatic group, and their binding mechanism with aphid OBPs was studied. In present study, to clarify the effects of linkers on the bioactivities of salicylate-substituted EBF derivatives against the aphid, a new series of salicylate-substituted EBF derivatives with an acylamino linker was designed and synthesized by the bioisosterism strategy. Their aphid-repellent activities, binding mechanisms with aphid OBPs, and aphicide activities were compared. The bioassay results indicated that salicylate-substituted EBF derivatives with a carboxyl linker showed higher aphid-repellent and OBP binding activities than the derivatives with an acylamino-linker. The molecular dynamic simulations and MM/GBSA calculation suggested that a more excellent hydrophobic linker such as carboxyl linker was essential for binding activity due to its stronger interactions with surrounding amino acids of the target proteins. Nevertheless, the salicylate substituted EBF derivatives with an acylamino linker exhibited significantly higher aphicidal activities than those with a carboxyl linker. In addition, the scaffold structure of EBF was essential to maintain the inherent aphid-repellent activity, target OBPs binding, and aphicidal activity. This work provides valuable guidelines for the rational design of different aphid control agents. [Display omitted] [ABSTRACT FROM AUTHOR]

• A novel cocrystal structure of levofloxacin and nicotinic acid is proposed. • The cocrystal exhibits unique properties of thermoanalysis, fourier transform infrared spectrum and X-ray powder diffraction spectrum. • An obvious advantage in improving the water solubility, that is 5.02 times higher than the original levofloxacin, was exhibited by the cocrystal. A novel chemical structure named pharmaceutical cocrystal was synthesized with the purpose to enhance the solubility of levofloxacin (LVFX). Nicotinic acid (NA) was selected as cocrystal coformer (CCF). The cocrystal was successfully obtained by solvent evaporation method combined with ultrasonic technology. The crystal structure of LVFX-NA is triclinic with a P1 space group, unit cell parameters a = 7.1392 Å, b = 10.0188 Å, c = 17.5394 Å, α=86.109 (7), β=86.082 (6), γ=73.809 (7), z = 2, R1=0.0518, ωR2=0.1425. The supramolecular structure of LVFX-NA is mainly controlled by O H···N and C H···O intermolecular hydrogen bond. Moreover, intramolecular hydrogen bonds C H···F have also been found in the cocrystal structural units. The obtained cocrystal exhibits unique properties of thermoanalysis, Fourier transform infrared (FT-IR) spectrum and X-ray powder diffraction (PXRD) spectrum, demonstrated the new formed crystal material. Equilibrium solubility measurement revealed that LVFX-NA exhibited improved aqueous solubility, that is 5.02 times higher than the original LVFX. [ABSTRACT FROM AUTHOR]

• The PRO-BPE cocrystal was prepared using an ultrasonication-assisted solvent evaporation method. • The PRO-BPE cocrystal has been successfully synthesized for the first time. • The solubility of PRO has been increased by a factor of 2.43 using cocrystallization technology for the first time. To improve the bioavailability and provide a lead compound for developing formulations of the highly water-insoluble prodrug probenecid (PRO), enhancing its solubility is a crucial challenge that needs to be addressed. Herein, we report the synthesis and solid-state characterization of a new pharmaceutical cocrystal, PRO-BPE, synthesized using trans-1,2-bis(4-pyridyl)ethylene (BPE) to improve the solubility of PRO. The PRO-BPE cocrystals were characterized using various analytical techniques, including differential scanning calorimetry, thermogravimetric analysis, scanning electron microscopy, Fourier transform-infrared spectroscopy, and X-ray powder diffraction. Single-crystal X-ray diffraction was performed to determine the crystal structure of PRO-BPE. PRO-BPE crystallized in the triclinic crystal system P-1 space group and its asymmetric unit consists of half a BPE molecule and one PRO molecule. The N1 atoms located at both ends of the BPE molecule form stable hydrogen bonds with two PRO carboxyl hydrogens through N1···H4—O4 (1.777 Å, 166.78°) interactions, whereas the O3 atoms of the carboxylic groups form C1—H1···O3 (2.479 Å, 132.10°) hydrogen bonds with two pyridyl hydrogens, resulting in a stable seven-membered ring structure. Furthermore, these fragments are further assembled via C—H···O intermolecular interactions to form a two-dimensional layered structure. Interestingly, the two pyridyl rings of each BPE molecule engage in π···π interactions with the benzene rings of two other non-coplanar PRO molecules. Finally, a three-dimensional framework structure is formed through intramolecular non-covalent interactions. Comprehensive characterization analyses provided further information regarding PRO-BPE cocrystal formation. Based on the equilibrium solubility results, the water solubility of the PRO-BPE cocrystal was superior to that of pure PRO, with an increase of 2.43 times. In summary, this study provides the first evidence that cocrystals could enhance the solubility of PRO and offers valuable insights into the solid-state properties of PRO-BPE cocrystals. [ABSTRACT FROM AUTHOR]

• The PRO-BPE cocrystal was prepared using an ultrasonication-assisted solvent evaporation method. • The PRO-BPE cocrystal has been successfully synthesized for the first time. • The solubility of PRO has been increased by a factor of 2.43 using cocrystallization technology for the first time. To improve the bioavailability and provide a lead compound for developing formulations of the highly water-insoluble prodrug probenecid (PRO), enhancing its solubility is a crucial challenge that needs to be addressed. Herein, we report the synthesis and solid-state characterization of a new pharmaceutical cocrystal, PRO-BPE, synthesized using trans-1,2-bis(4-pyridyl)ethylene (BPE) to improve the solubility of PRO. The PRO-BPE cocrystals were characterized using various analytical techniques, including differential scanning calorimetry, thermogravimetric analysis, scanning electron microscopy, Fourier transform-infrared spectroscopy, and X-ray powder diffraction. Single-crystal X-ray diffraction was performed to determine the crystal structure of PRO-BPE. PRO-BPE crystallized in the triclinic crystal system P-1 space group and its asymmetric unit consists of half a BPE molecule and one PRO molecule. The N1 atoms located at both ends of the BPE molecule form stable hydrogen bonds with two PRO carboxyl hydrogens through N1···H4—O4 (1.777 Å, 166.78°) interactions, whereas the O3 atoms of the carboxylic groups form C1—H1···O3 (2.479 Å, 132.10°) hydrogen bonds with two pyridyl hydrogens, resulting in a stable seven-membered ring structure. Furthermore, these fragments are further assembled via C—H···O intermolecular interactions to form a two-dimensional layered structure. Interestingly, the two pyridyl rings of each BPE molecule engage in π···π interactions with the benzene rings of two other non-coplanar PRO molecules. Finally, a three-dimensional framework structure is formed through intramolecular non-covalent interactions. Comprehensive characterization analyses provided further information regarding PRO-BPE cocrystal formation. Based on the equilibrium solubility results, the water solubility of the PRO-BPE cocrystal was superior to that of pure PRO, with an increase of 2.43 times. In summary, this study provides the first evidence that cocrystals could enhance the solubility of PRO and offers valuable insights into the solid-state properties of PRO-BPE cocrystals. [ABSTRACT FROM AUTHOR]

• Urolithin A was a reversible and uncompetitive inhibitor of α -glucosidase. • Urolithin A statically quenched the endogenous fluorescence of α -glucosidase. • Urolithin A combined with acarbose showed an additive inhibitory effect. • Urolithin A interacted with α -glucosidase by key residues Arg269, Thr273, and His258. In this study, the mechanism of interaction between urolithin A, a gut metabolite of ellagitannins, and α -glucosidase was characterized by inhibition kinetics, fluorescence spectroscopy, isothermal titration calorimetry, and molecular docking. Urolithin A exhibited potential reversible inhibitory activity for α -glucosidase in an uncompetitive manner with an IC 50 value of (28.03 ± 0.59) μ M. The results of fluorescence titration and isothermal titration calorimetry analysis showed that urolithin A statically quenched the endogenous fluorescence of α -glucosidase, which was a spontaneous exothermic process, mainly driven by hydrogen bond and/or van der Waals force. Synchronous fluorescence spectroscopy revealed that urolithin A increased the polarity of tryptophan microenvironment and the hydrophobicity of tyrosine microenvironment. The combination of urolithin A with acarbose, a competitive α -glucosidase inhibitor, showed an additive inhibitory effect. Furthermore, molecular docking showed that urolithin A formed hydrogen bonds with key residues Arg269, Thr273, and His258, which are the sites outside the active center of α -glucosidase. These findings could highlight the value of ellagitannin rich diet as an antihyperglycemic food in the prevention of postprandial hyperglycemia, and indicate that urolithin A may be a promising lead compound of α -glucosidase inhibitor. [Display omitted] [ABSTRACT FROM AUTHOR]