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A series of new thiophene-containing triaryl pyrazoline derivatives, 3a–3t, were synthesized and evaluated regarding PI3K inhibition activity and anti-tumor potency based on a trial of introducing significant moieties, including pyrazoline and thiophene, and simplifying the parallel ring structures. Most of the tested compounds indicated potent PI3K inhibitory potency, with this series of compounds showing more potency for PI3Kγ than PI3Kα. The top hit 3s seemed more potent than the positive control LY294002 on inhibiting PI3Kγ (IC50 values: 0.066 μM versus 0.777 μM) and more selective from PI3Kα (Index values: 645 versus 1.74). It could be inferred that the combination of para- and meta-, as well as the modification of the electron-donating moieties, led to the improvement in potency. The anti-proliferation inhibitory activity and the enzymatic inhibition potency indicated consistent tendencies. The top hit 3s could inhibit the phosphorylation of Akt by inhibiting PI3K through the PI3K-Akt-mTOR pathway. The molecular docking simulation indicated that the binding pattern of 3s into PI3Kγ was preferable than that of PI3Kα, with more hydrogen bond, more π-involved interactions, and fewer π-sulfur interactions. The information in this work is referable for the further development of selective inhibitors for specific isoforms of PI3K. [ABSTRACT FROM AUTHOR]

A series of new thiophene-containing triaryl pyrazoline derivatives, 3a–3t, were synthesized and evaluated regarding PI3K inhibition activity and anti-tumor potency based on a trial of introducing significant moieties, including pyrazoline and thiophene, and simplifying the parallel ring structures. Most of the tested compounds indicated potent PI3K inhibitory potency, with this series of compounds showing more potency for PI3Kγ than PI3Kα. The top hit 3s seemed more potent than the positive control LY294002 on inhibiting PI3Kγ (IC50 values: 0.066 μM versus 0.777 μM) and more selective from PI3Kα (Index values: 645 versus 1.74). It could be inferred that the combination of para- and meta-, as well as the modification of the electron-donating moieties, led to the improvement in potency. The anti-proliferation inhibitory activity and the enzymatic inhibition potency indicated consistent tendencies. The top hit 3s could inhibit the phosphorylation of Akt by inhibiting PI3K through the PI3K-Akt-mTOR pathway. The molecular docking simulation indicated that the binding pattern of 3s into PI3Kγ was preferable than that of PI3Kα, with more hydrogen bond, more π-involved interactions, and fewer π-sulfur interactions. The information in this work is referable for the further development of selective inhibitors for specific isoforms of PI3K.

A series of thieno-pyrimidine derivatives are synthesized from 5′-amino-2,3′-bithiophene-4′-carboxylate via the corresponding intermediate N-benzoylated carboxamide derivatives. The target compounds are tested for antibacterial and antifungal activity. Some of the synthesized compounds demonstrate potent antibacterial activity with LD50 comparable with the reference drug indomethacin. [ABSTRACT FROM AUTHOR]

Abstract: Chlorination of bis(1-naphthyl)ditelluride (NplTeTeNpl; Npl=1-C10H7) with 3 equiv. of sulfuryl chloride (SO2Cl2) resulted in bright yellow crystals of 1-naphthyltellurium(IV) trichloride (1-NplTeCl3; 1). Bis(mesityl)tellurium(IV) dichloride, Mes2TeCl2, 2 (Mes=2,4,6-Me3C6H2) has been synthesized by the oxidative addition of sulfuryl chloride to bis(mesityl)telluride(II), prepared from detelluration of bis(mesityl)ditelluride with a freshly prepared electrolytic copper. Bis(chlorobis(2-thiophenyl)tellurium)oxide, (Tpn2TeCl)2O, 3 (Tpn=2-C4H3S) have been obtained serendipitously as a product of reaction between bis(thiophenyl)tellurium(IV) dichloride (Tpn2TeCl2) and AgCN. All the three compounds 1–3 have been characterized crystallographically. In crystal lattice of 1, an asymmetric unit consists of two independent molecules and both the molecules form a separate polymeric zig-zag chains via μ2-chloro bridging. These two polymeric chains are interlinked via C−H⋯Cl H-bonding interactions to form a one dimensional supramolecular array. In case of 2 a dimeric unit has been realized through C−H⋯Cl H-bonding interaction while in 3 a one dimensional supramolecular array has been formed via intermolecular Te⋯Cl1 secondary bonding interactions, where both the tellurium atoms exhibit ψ-trigonal bipyramidal geometry. [Copyright &y& Elsevier]

[Display omitted] • The design of double Schiff base sensors (R and E) improved detection efficiency for target ions. • R and E showed high sensitivity to gallium ions with the ultralow detection limits of 3.90 nM and 3.97 nM, respectively. • The improved sensor E possessed excellent sensing performance for Ga3+, such as the super anti-interference ability. • The superior fluorescence properties of E were explained systematically through theoretical calculations. • E offered versatile platforms for Ga3+ detection in practical applications such as tap water sample and test strips. Two thiophene-derived symmetrical Schiff bases R ( N'2 , N'5 -bis((E)-2-hydroxybenzylidene)thiophene-2,5-dicarbohydrazide) and E ( N'5 , N'7 -bis((E)-2-hydroxybenzylidene)-2,3-dihydrothieno[3,4- b ][1,4]dioxine-5,7-dicarbohydrazide) were synthesized as sensors for Ga3+ detection via fluorescence turn-on strategy. After chelation with Ga3+, both of them displayed the significant fluorescence enhancement in MeCN/H 2 O buffer solution. Meanwhile, R and E showed ultralow detection limits of 3.90 × 10−9 M and 3.97 × 10−9 M, respectively. Differently, the sensor E featured much higher selectivity and anti-interference for Ga3+ detection than R in the presence of other cations such as In3+, Zn2+ and Cu2+. The Job's plots revealed a 1:2 stoichiometry between sensors and Ga3+ with the association constant of 3.89 × 109 M2 for R and 8.59 × 109 M2 for E , respectively. To further explain the differences of sensing performance between the two sensors, the theoretical researches were executed through the molecular configuration, charge distribution, molecular orbitals, electronic transitions and energy variation. Besides, E could exhibit an efficient recognition of Ga3+ in the water samples. [ABSTRACT FROM AUTHOR]

Seven new Schiff bases, which are 4,4,4-trifluorol-(2-thienyl)-l-butanone-3-Z, Z=-thiosemicarbazone ( a); -thiocarbohydrazone ( b),-benzoic hydrazone ( c), -( o-hydroxyphenyl) imine ( d) ,-nicotinic hydrazone ( e) ,-salicylic hydrazone ( f), and -( p-fluoro- m-chlorophenyl) imine ( g), have been synthesized by reaction of 4, 4, 4-trifluoro-1-(2-thienyl)-l, 3-butanedione (TFTBD) with corresponding hydrazides or anilines, acetic acid or p-toluence sulfonic acid as catalyst, and characterized by Elemental analysis, IR, UV-Vis.1H NMR and MS. The MS spectra confirmed that the −C3=0 condensed with primary amino group. Tautomerism of the compounds is discussed. [ABSTRACT FROM AUTHOR]

Abstract: A new MMP12 inhibitor series has been identified containing a thiophene moiety. Different approaches have been considered to replace this potential toxicophore. α-Fluorothiophene derivatives were the most interesting compounds. Their synthesis is presented. [Copyright &y& Elsevier]