Synthesis, Phase Behavior and Computational Simulations of a Pyridyl-Based Liquid Crystal System

A homologous set of liquid crystalline materials (Tn) bearing Schiff base/ester linkages were prepared and investigated via experimental and theoretical techniques. Terminal flexible groups of different chain lengths were connected to the end of phenylbenzoate unit while the other end of molecules was attached to the heterocyclic pyridine moiety. The molecular structures of the designed molecules were evaluated by FT-IR, NMR spectroscopic analyses, whereas their mesomorphic properties were investigated by polarized optical microscopy (POM) and differential scanning calorimetry (DSC). They all exhibited dimorphic properties with the exception of the members having the shortest and longest terminal flexible chains (n = 6 and 16), which were monomorphic. The T16 derivative was further found possessing purely smectic A (SmA) mesophase while others have their lengths covered by nematic (N) phase. Moreover, the computational evaluation of the azomethine derivatives was carried out using a DFT approach. The polarity of the investigated derivatives was predicted to be appreciably sensitive to the size of the system. Furthermore, the Frontier molecular orbitals analysis revealed various distributions of electron clouds at HOMO and LUMO levels.

New pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-one hybrids linked to arene units: synthesis of potential MRSA, VRE, and COX-2 inhibitors

In the current study, we reported the tandem synthesis of two series of arene-linked pyrimidinone hybrids with related fused thieno[2,3-b]pyridine moiety. The target hybrids were prepared, in moderate to excellent yields, by the reaction of a ternary mixture of the appropriate of 3-aminothieno[2,3-b]pyridine-2-carboxylate, DMF-DMA, and a series of aryl amines in dioxane at 110 °C for 8 h. The antibacterial activity of the new hybrids was estimated against six susceptible ATCC strains. Hybrids 5g and 7g, linked to a sulfonamide unit, showed the best efficacy against S. aureus and E. faecalis strains with minimum inhibitory concentration (MIC) values of 1.7–1.8 μM, which exceed ciprofloxacin. Furthermore, some of new hybrids were examined as potential inhibitors of four different MRSA and VRE strains. Hybrids 5g and 7g demonstrated more potent efficacy than linezolid against MRSA strains with MIC values of 3.6/3.4 and 1.8/1.7 μM against ATCC:33591 and ATCC:43300 strains, respectively. The prior hybrids displayed a comparable efficacy with linezolid against VRE strains with MIC values of 7.3/6.9 and 3.6/3.4 μM against ATCC:51299 and ATCC:51575 strains, respectively. Additionally, some of the new hybrids were examined as potential COX-2 inhibitors using the reference celecoxib (IC50 of 0.117 µM). Hybrid 7g revealed more potent inhibitory efficacy than celecoxib with IC50 of 0.112 µM, whereas hybrid 5g showed almost inhibitory activity equivalent to celecoxib with IC50 of 0.121 µM. Molecular docking was performed to predict the possible binding interactions between hybrids 5g and 7g with the target COX-2 enzyme.

Synthesis, Crystal Structure, Inhibitory Activity and Molecular Docking of Coumarins/Sulfonamides Containing Triazolyl Pyridine Moiety as Potent Selective Carbonic Anhydrase IX and XII Inhibitors

In this work, two classes of Carbonic Anhydrase (CA) inhibitors, sulfonamide and coumarin derivatives linked to pyta moiety (2a-b) and their corresponding rhenium complexes (3a-b), were designed. These compounds were synthesized and fully characterized by classical analytical methods and X-ray diffraction. All the synthesized compounds were evaluated for their inhibitory activity against the hCA isoforms I, II, IX and XII. They exhibited high inhibitory activities in the range of nanomolar for both hCA IX and hCA XII isoforms. The sulfonamide compound 2a showed the strongest inhibition against the tumour-associated hCA IX isoform with a Ki of 11.7 nM. The tumour-associated isoforms hCA IX and hCA XII were selectively inhibited by all the coumarin derivatives, with inhibition constants ranging from 12.7 nM (2b) to 44.5 nM (3b), while the hCA I and II isoforms were slightly inhibited (in the micromolar range), as expected. In terms of selectivity, compared to previously published rhenium complex-based CA inhibitors, complex 3b showed one of the highest selectivities against hCA IX and hCA XII compared to the off-target isoforms hCA I and hCA II, making it a potential anti-cancer drug candidate. Molecular docking calculations were performed to investigate the inhibition profiles of the investigated compounds at the tumour-associated hCA IX active site and to rationalize our results.

Macathiohydantoin L, a Novel Thiohydantoin Bearing a Thioxohexahydroimidazo [1,5-a] Pyridine Moiety from Maca (Lepidium meyenii Walp.)

Five new thiohydantoin derivatives (1–5) were isolated from the rhizomes of Lepidium meyenii Walp. NMR (1H and 13C NMR, 1H−1H COSY, HSQC, and HMBC), HRESIMS, and ECD were employed for the structure elucidation of new compounds. Significantly, the structure of compound 1 was the first example of thiohydantoins with thioxohexahydroimidazo [1,5-a] pyridine moiety. Additionally, compounds 2 and 3 possess rare disulfide bonds. Except for compound 4, all isolates were assessed for neuroprotective activities in corticosterone (CORT)-stimulated PC12 cell damage. Among them, compound (−)-3 exhibited moderate neuroprotective activity (cell viability: 68.63%, 20 μM) compared to the positive control desipramine (DIM) (cell viability: 88.49%, 10 μM).