In silico studies of novel scaffold of thiazolidin-4-one derivatives as anti-Toxoplasma gondii agents by 2D/3D-QSAR,molecular docking,and molecular dynamics simulations

Structural Chemistry - Toxoplasma gondii is an obligate intracellular protozoa that can infect a wide variety of warm-blooded animals and humans. It was claimed that novel anti-Toxoplasma gondii...     

6-异位-5,8-O-二甲基乙酰紫草素衍生物的2D/3D-QSAR研究

本文综合运用密度泛函理论(DFT)、分子力学(MM2)和统计学等方法对22个具有抗人体乳腺癌(MDA-MB-231)活性的6-异位-5,8-O-二甲基乙酰紫草素类衍生物进行二维(2D)定量构效关系(QSAR)研究,同时运用比较分子相似性指数分析(Co MSIA)方法进行三维(3D)QSAR研究。所建最优2D-QSAR方程的留一法交叉验证系数(q2)和拟合相关系数(R2)分别为0.833和0.900;Co MSIA(SEHA)模型的q2和非交叉验证系数(r2)分别为0.624和0.999,预测相关系数R2pred为0.838,表明所建立的2D/3D-QSAR模型都具有良好的统计学意义及合理、可信的预报能力,可以预测未知化合物的活性。研究结果为理解该类化合物的作用机理和设计合成更高活性的新化合物提供理论参考。     

Author Correction to: In silico studies of novel scaffold of thiazolidin-4-one derivatives as anti-Toxoplasma gondii agents by 2D/3D-QSAR,molecular docking,and molecular dynamics simulations

Structural Chemistry - The authors regret that the Acknowledgments of the original version of this article was incorrect.     

Lifetime measurements of the 3D3/2 and 3D5/2 metastable states in CaII

The lifetime of the metastable 3D_3/2 and 3D_5/2 states of Ca⁺ ions is determined in a r.f. ion trap by laser excitation of this levels and subsequent time delayed probing of the state population by a second laser. In a buffer gas atmosphere of about 10^–5–10^–6 mbar of He we observe quenching to the ground state and strong finestructure mixing of the two D-states. This mixing allowes only the determination of the combined lifetime. Our result of (3D)=1.24(39) s is in good agreement with theoretical calculations.     

A new route to 2'-O-alkyl-2-thiouridine derivatives via 4-O-protection of the uracil base and hybridization properties of oligonucleotides incorporating these modified nucleoside derivatives

Oligonucleotides containing 2-thiouridine (s2U) in place of uridine form stable RNA duplexes with complementary RNAs. Particularly, this modified nucleoside has proved to recognize highly selectively adenosine, the genuine partner, without formation of a mismatched base pair with the guanosine counterpart. In this paper, we describe new methods for the synthesis of 2-thiouridine and various 2'-O-alkyl-2-thiouridine derivatives. Oligoribonucleotides having these modified nucleoside derivatives were synthesized, and their hybridization and structural properties were studied in detail by the 1H NMR analysis of these modified nucleosides and Tm experiments of RNA duplexes with their complementary RNA strands.     

Pyridazine derivatives. Part 40: Reactivity of 5-alkynylpyridazin-3(2H)-ones toward hydrochloric acid

5-Alkynylpyridazin-3(2H)-ones or 5-(2-chloroalkenyl)pyridazin-3(2H)-ones were isolated during the cleavage of the methoxymethyl group in a series of 5-alkynyl-2-methoxymethylpyridazin-3(2H)-ones by treatment with hydrochloric acid. The efficient and selective cleavage of the methoxymethyl group in these compounds can be performed under mild conditions by employing aluminium chloride.     

Improved lifetime measurements of the 3D3/2 and 3D5/2 metastable states of Ca II

The lifetimes of both metastable 3D-levels of Ca⁺ have been measured using the ion storage technique. Operation at UHV-conditions eliminated the earlier reported problems of collisional finestructure mixing between those states [1], which is inherent to measurements at buffergas background. The results of τ(D _3/2)=1113(45) ms and τ(D _5/2)=1054(61) ms improve our earlier result [1] by almost one order of magnitude and are in good agreement with recent theoretical calculations [3, 4, 5].     

Cyclopalladation compounds of the 2-pyridylhydrazone derivatives of p-substituted acetophenones and acetylthiophenes

Cyclopalladation occurs for 2-pyridylhydrazones(HL) of p-methyl-, p-methoxy-, p-chloro-, and p-nitro-acetophenone, and 3-acetyl- and 2-acetyl-thiophene with lithium tetrahalopalladate to give the complexes [PdXL] (X = Cl and Br) and some iodo complexes are prepared by metathesis of the chloro complexes with lithium iodide. These complexes are characterized spectroscopically. The hydrazones are coordinated to palladium through benzene or thiophene ortho-carbon, hydrazone-nitrogen, and pyridine ring-nitrogen atoms forming fused five-membered chelate rings.     

Nitrogen bridgehead compounds. Part 69. Studies on quinolizine derivatives. Part 3. Infrared and 1H NMR spectroscopic studies of quinolizine derivatives and their monocyclic tautomers

Infrared and ¹H nmr spectra of 4-oxo, 1 , and 4-imino, 2 , quinolizine derivatives or their monocyclic tautomers 3, 4 have been comparatively studied. The number of ethoxycarbonyl groups, the signals of the hetero proton, the C(9)-H, and the C(6)-CH₃ group in the ¹H nmr spectrum, moreover the N-H stretching vibration bands proved to be diagnostically important for monocyclic or bicyclic as well as for 4-oxo or 4-imino structures. A weak intramolecular hydrogen bridge in compounds 2b and 2f , a strong chelate type hydrogen bridge in 4E and 4F=G could have been demonstrated as well.     

A new enlargement methodology for the preparation of 2H-1- and 2H-3-benzazepin-2-one derivatives

An investigation of the one-carbon homologation of some 1-tribromomethyl-isoquinoline and 2-tribromomethyl-quinoline derivatives was conducted. Under the influence of an aqueous solution of silver nitrate in the presence of a nucleophilic species (MeOH, H₂O, EtNH₂), these derivatives led to the respective expanded heterocycles, 2H-1- and 2H-3-benzazepin-2-one derivatives. A mechanism for this novel ring enlargement involving initial formation of an aziridinium, and its subsequent opening to form a stabilized benzylic carbocation, is proposed to explain the results.     

Design,synthesis, antitubercular and antibacterial activities of pyrrolo[3,2-b]pyridine-3-carboxamide linked 2-methoxypyridine derivatives and in silico docking studies

Abstract

A novel series pyrrolo[3,2-b]pyridine-3-carboxamide linked 2-methoxypyridine derivatives have been designed, synthesized and confirmed by FT-IR, ¹H NMR, ¹³C NMR, ¹⁹F NMR, MS, and elemental analysis. The synthesized compounds were screened for their antitubercular activity using microplate alamar blue assay method and antibacterial activity. Among the tested compounds, 4- fluorophenyl (8m), 4- chlorophenyl (8n) and 4-methoxyphenyl (8i) showed potent anti-TB activity (3.12?µg/mL) in comparison with reference drug, Pyrazinamide ((3.12?µg/mL). In addition, all compounds were docked into DprE1 (PDB code: 4KW5) to explore their binding interactions at the active site. The compounds exhibited essential key interactions as that of reported DprE1 inhibitors and hence, the synthesized compounds may be considered as molecular scaffolds for antitubercular activity. Compounds, 4-chlorophenyl (8n) and 4-flurophenyl (8m) showed significant antibacterial activity against Escherichia coli and Staphylococcus aureus strains. In silico prediction of toxicities, druglikeness and drug score profiles of the tested compounds are promising.