排序方式: 共有50条查询结果,搜索用时 31 毫秒
1.
The serine protease, DegP exhibits proteolytic and chaperone activities, essential for cellular protein quality control and normal cell development in eukaryotes. The P. falciparum DegP is essential for the parasite survival and required to combat the oscillating thermal stress conditions during the infection, protein quality checks and protein homeostasis in the extra-cytoplasmic compartments, thereby establishing it as a potential target for drug development against malaria. Previous studies have shown that diisopropyl fluorophosphate (DFP) and the peptide SPMFKGV inhibit E. coli DegP protease activity. To identify novel potential inhibitors specific to PfDegP allosteric and the catalytic binding sites, we performed a high throughput in silico screening using Malaria Box, Pathogen Box, Maybridge library, ChEMBL library and the library of FDA approved compounds. The screening helped identify five best binders that showed high affinity to PfDegP allosteric (T0873, T2823, T2801, , CD00811) and the catalytic binding site (T0078L, T1524, T2328, BTB11534 and 552691). Further, molecular dynamics simulation analysis revealed RJC02337, BTB11534 as the best hits forming a stable complex. WaterMap and electrostatic complementarity were used to evaluate the novel bio-isosteric chemotypes of RJC02337, that led to the identification of 231 chemotypes that exhibited better binding affinity. Further analysis of the top 5 chemotypes, based on better binding affinity, revealed that the addition of electron donors like nitrogen and sulphur to the side chains of butanoate group are more favoured than the backbone of butanoate group. In a nutshell, the present study helps identify novel, potent and Plasmodium specific inhibitors, using high throughput in silico screening and bio-isosteric replacement, which may be experimentally validated. RJC02337相似文献
2.
3.
Wenhua Chen Xue Yao Zhenghui Huang Fei Mao Longfei Guan Yun Tang Hualiang Jiang Jian Li Jin Huang Lubin Jiang Jin Zhu 《中国化学快报》2019,30(1):250-254
A series of novel 2,4-diaminopyrimidine-modified compounds was designed and synthesized. Compound 14 showed micromolar dual inhibitory effect on both FP-2 and PfDHFR, and potential inhibition to the proliferation of P. falciparum 3D7 strain and chloroquine-resistant P. falciparum Dd2 strain. 相似文献
4.
DIHALOCARBENE ADDITION TO ARYLSUBSTTTUTED VINYL PHOSPHATES UNDER PHASE TRANSFER CATALYTIC CONDITIONS
Imre Petneházy György Keglevich László Tőke 《Phosphorus, sulfur, and silicon and the related elements》2013,188(1-2):77-82
Abstract Dihalocarbene addition to aryl-substituted vinyl phosphates was carried out both in solid-liquid and in liquid-liquid two phase systems. The dihalocyclopropane adducts of vinyl phosphates could be obtained in better yield using dihalocarbenes generated by the latter method and no hydrolysis of the vinyl phosphate and of the adduct occurred under these circumstances. Eighteen new vinyl phosphate-dihalocarbene adducts were synthetized and characterized. 相似文献
5.
6.
Eti Mehrotra Jyotsna Vishwakarma Avinash C. Tripathi Pankaj K. Sonar 《Natural product research》2019,33(4):568-572
The present study explored the schizonticidal potential of traditionally used Magnolia champaca (L.) Baill. ex. Pierre flowers, identifying constituents of interest. The extraction of phytoconstituents was carried out by microwave-assisted technique, isolated via column chromatography, and characterised by various physicochemical, spectral (IR, 1H-NMR and Mass) and chromatographic (HPTLC) techniques. Both the isolated compounds (parthenolide and costunolide diepoxide) exhibited potent schizonticidal antimalarial activity during primary screening in rodent models, with maximum parasitaemia suppression (85.18% and 83.65%, respectively) at a dose of 20 mg/kg body weight when compared to the standard drugs chloroquine and artesunate. In silico techniques were employed to identify the probable biological target and mechanism of action of these isolated compounds. Molecular docking studies also predicted the binding orientations and multi-targeted action of these compounds, in particular costunolide diepoxide with maximum affinity towards SERCA and DHFR proteins. Additionally, favourable in silico ADMET parameters were envisaged through various computational programmes. 相似文献
7.
Vanessa Gisele Pasqualotto Severino Cristiane de Melo CazalMoacir Rossi Forim Maria Fátima das Graças Fernandes da SilvaEdson Rodrigues-Filho João Batista FernandesPaulo Cezar Vieira 《Journal of chromatography. A》2009,1216(19):4275-4281
High-speed counter-current chromatography (HSCCC) with a two-phase solvent system (hexane–ethanol–acetonitrile–water 10:8:1:1, v/v) was applied to examine the leaves of Hortia oreadica, which afforded the known limonoid guyanin (1), the alkaloids rutaecarpin (2) and dictamnine (6), the dihydrocinnamic acid derivatives methyl 5,7-dimethoxy-2,2-dimethyl-2H-1-benzopyran-6-propanoate (3), 5,8-dimethoxy-2,2-dimethyl-2H-1-benzopyran-6-propanoic acid (4), together with the new E-3,4-dimethoxy-α(3-hydroxy-4-carbomethoxyphenyl)cinnamic acid (5). The recovery of compounds 1–6 was determined by comparison with LC-atmospheric pressure chemical ionization MS/MS data: 66.2%, 93.1%, 102.5%, 101.2%, 99.0% and 84.9%, respectively. Compound 3 showed IC50 of 23.6 μM against Plasmodium falciparum and 15.6 μM against Trypanosoma brucei rhodesienses and was not toxic to KB cells (IC50 > 100 μM). 相似文献
8.
9.
Guillaume Anquetin 《Tetrahedron》2005,61(35):8394-8404
In the search for new potent antiparasitical fluoroquinolones, a QSAR analysis by molecular connectivity led to the design of R5 (Me or Et)/R8 (MeO, Me or Et)-substituted analogs of the most powerful antibacterial or antiparasitical fluoroquinolones known so far. Unfortunately, the synthetic schemes that were elaborated in literature for 3- and 3,6-di-substituted 2,4,5-trifluorobenzoic acids, the key precursors of the target R5/R8-substituted 6-fluoroquinolones, led in our hands to poor yields and/or to inextricable mixtures of derivatives. This led us to reinvestigate the key alkylation steps of the 2,4,5-trifluorophenyl-oxazoline synthons and the subsequent deprotection of their oxazoline into acid with the aim of optimising the syntheses of 3- and 3,6-di-substituted 2,4,5-trifluorobenzoic acids, which constitute the entries to our target derivatives. 相似文献
10.
Satomi Nakatani Masaaki Sato Hiroshi Hirota Masami Ishibashi 《Tetrahedron letters》2005,46(2):267-271
Melleumin A (1), a novel peptide lactone, has been isolated from the laboratory-cultured plasmodium of myxomycete Physarum melleum, and its structure was elucidated by spectral data. Melleumin A (1) consisted of four residues (p-methoxybenzoic acid, l-threonine, glycine, and an unusual amino acid, a tyrosine-attached acetic acid). 相似文献