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51.
52.
Disulfated and trisulfated steroids have been synthesized from cholesterol and their acetylcholinesterase inhibitory activity has been evaluated. In our studies we have found that the activity was not only dependent on the location of the sulfate groups but on their configurations. 2β,3α,6α-trihydroxy-5α-cholestan-6-one trisulfate (18) was the most active steroid with an IC50 value of 15.48 μM comparable to that of 2β,3α-dihydroxy-5α-cholestan-6-one disulfate (1). Both compounds were found to be less active than the reference compound eserine. The butyrylcholinesterase activity of 1 and 18 was one magnitude lower than that against acetylcholinesterase revealing a selective inhibitor profile. 相似文献
53.
Li-Ping Shi Kun-Ming Jiang Jun-Jie Jiang Yi Jin Yun-Hai Tao Ke Li Xing-Hong Wang Jun Lin 《Bioorganic & medicinal chemistry letters》2013,23(21):5958-5963
A novel series of polyhalobenzonitrile quinazolin-4(3H)-one derivatives were synthesized and characterized by NMR, IR, MS, and HRMS spectra. All of the newly prepared compounds were screened for antimicrobial activities against four strains of bacteria (Gram-positive bacterial: Staphylococcus aureus and Bacillus cereus; Gram-negative bacterial: Escherichia coli and Pseudomonas aeruginosa) and one strain of fungi (Candida albicans). Among the synthesized compounds, 5-(dimethylamino)-8-(2,4,5-trichloro-isophthalonitrile) quinazolin-4(3H)-one (7k) exhibited significant activity towards Gram-positive bacterial, Gram-negative bacterial, and the fungi strains. The MIC (0.8–3.3 μg/mL) and MBC (2.6–7.8 μg/mL) for this compound were close to those of nofloxacin, chlorothalonil, and fluconazole, making it the most potent antimicrobial agents in the series. 相似文献
54.
Wiesław Malinka Piotr Świątek Małgorzata Śliwińska Bogumiła Szponar Andrzej Gamian Zbigniew Karczmarzyk Andrzej Fruziński 《Bioorganic & medicinal chemistry》2013,21(17):5282-5291
In this paper we describe synthesis, structures and some physicochemical properties of 20 isothiazolopyridines 8–13 substituted differently into an isothiazole ring as well as their in vitro antibacterial assays against Mycobacterium tuberculosis H37Rv, Mycobacterium fortuitum PCM 672 and Propionibacterium acnes PCM 2400. Compound 13a was found to be the most active derivative against M. tuberculosis H37Rv, demonstrating 100% growth inhibition of microorganisms in the primary screen (minimum inhibitory concentration [MIC] 6.25 μg/mL). Nineteen of the prepared compounds were evaluated against M. fortuitum PCM 672 and P. acnes PCM 2400 and only compounds 9 and 12d exhibited excellent activity against individual strains of microorganisms with MIC90 <1 μg/mL. The inhibitory action of the remaining isothiazolopyridines towards the tested strains of the microorganism was low, absent, or a non-linear correlation prohibited accurate determination of MIC values. Unexpectedly, seven of the remaining isothiazolopyridines tested against M. fortuitum and P. acnes stimulated growth of the microorganisms in the range 10–50% or even more (10b) under experimental conditions. 相似文献
55.
To discover multifunctional agents for the treatment of Alzheimer’s disease, a series of hydrazide based Schiff bases were designed and synthesized based on multitarget-directed strategy. We have synthesized twenty-eight analogs of hydrazide based Schiff bases, characterized by various spectroscopic techniques and evaluated in vitro for acetylcholinesterase and butyrylcholinesterase inhibition. All compounds showed varied degree of acetylcholinesterase and butyrylcholinesterase inhibition when compared with standard Eserine. Among the series, compounds 10, 3 and 24 having IC50 values 4.12 ± 0.01, 8.12 ± 0.01 and 8.41 ± 0.06 μM respectively showed potent acetylcholinesterase inhibition when compared with Eserine (IC50 = 0.85 ± 0.0001 μM). Three compounds 13, 24 and 3 having IC50 values 6.51 ± 0.01, 9.22 ± 0.07 and 37.82 ± 0.14 μM respectively showed potent butyrylcholinesterase inhibition by comparing with eserine (IC50 = 0.04 ± 0.0001 μM). The remaining compounds also exhibited moderate to weak inhibitory potential. Structure activity relationship has been established. Through molecular docking studies the binding interaction was confirmed. 相似文献
56.
《Bioorganic & medicinal chemistry》2016,24(23):6166-6173
Two series of Sorafenib derivatives bearing phenylpyrimidine–carboxamide moiety (16a–g and 17a–p) were designed, synthesized and evaluated for the IC50 values against three cancer cell lines (A549, MCF-7 and PC-3). Two selected compounds (17f and 17n) were further evaluated for the activity against VEGFR2/KDR kinase. More than half of the synthesized compounds showed moderate to excellent activity against three cancer cell lines. Compound 17f showed equal activity to Sorafenib against MCF-7 cell line, with the IC50 values of 6.35 ± 0.43 μM. Meanwhile, compound 17n revealed more active than Sorafenib against A549 cell line, with the IC50 values of 3.39 ± 0.37 μM. Structure–activity relationships (SARs) and docking studies indicated that the second series (17a–p) showed more active than the first series (16a–g). What’s more, the introduction of fluoro atom to the phenoxy part played no significant impact on activity. In addition, the presence of electron-donating on aryl group was benefit for the activity. 相似文献
57.
《Bioorganic & medicinal chemistry》2016,24(4):703-711
4-Amino- and 5-amino-cyclopropane pipecolic acids (CPAs) with cis relative stereochemistry between the carboxylic and amino groups were used as templates to prepare cyclic peptidomimetics containing the RGD sequence as possible integrin binders. The peptidomimetic c(RGD8) built on the 5-amino-CPA displayed an inhibition activity (IC50 = 2.4 nM) toward the αvβ3 integrin receptor (expressed in M21 human melanoma cell line) comparable to that of the most potent antagonists reported so far and it was ten times more active than the corresponding antagonist c(RGD7) derived from the isomeric 4-amino-CPA. Both compounds were also nanomolar ligands of the α5β1 integrin (expressed in human erythroleukemia cell line K562). These results suggest that the CPA-derived templates are suitable for the preparation of dual αvβ3 and α5β1 ligands to suppress integrin-mediated events as well as for targeted drug delivery in cancer therapy. 相似文献
58.
《Bioorganic & medicinal chemistry》2016,24(2):92-103
A series of (2-benzoylethen-1-ol)-containing benzothiazine derivatives was synthesized, and their herbicidal activities were first evaluated. The bioassay results indicated that some of 3-benzoyl-4-hydroxy-2-methyl-2H-1,2-benzothiazine-1,1-dioxide derivatives displayed good herbicidal activity in greenhouse testing, especially, compound 4w had good pre-emergent herbicidal activities against Brassica campestris, Amaranthus retroflexus and Echinochloa crusgalli even at a dosage of 187.5 g ha−1. More importantly, compound 4w displayed significant inhibitory activity against Arabidopsis thaliana HPPD and was identified as the most potent candidate with IC50 value of 0.48 μM, which is better than the commercial herbicide sulctrione (IC50 = 0.53 μM) and comparable with the commercial herbicide mesotrione (IC50 = 0.25 μM). The structure–activity relationships was studied and provided some useful information for improving herbicidal activity. The present work indicated that (2-benzoylethen-1-ol)-containing 1,2-benzothiazine motif could be a potential lead structure for further development of novel HPPD inhibiting-based herbicides. 相似文献
59.
《Bioorganic & medicinal chemistry》2016,24(9):1937-1980
New drugs introduced to the market every year represent privileged structures for particular biological targets. These new chemical entities (NCEs) provide insight into molecular recognition and also serve as leads for designing future new drugs. This annual review covers the synthesis of thirty-seven NCEs that were approved for the first time in 2014 and one drug which was approved in 2013 and was not covered in a previous edition of this review. 相似文献
60.
《Bioorganic & medicinal chemistry letters》2019,29(13):1673-1676
Organotellurium compounds have been reported as an immune-modulator sensitizing chemotherapeutics. Herein, we report the design and synthesis of a series of novel tellurodibenzoic acids as mimics of diphenylarsenic acid (DPAA) and potential selective KGA inhibitors. Representative compound 3B exhibited potent inhibition of KGA and glutamine-dependent HCT-116 cells. Stability experiments indicated that 3B has excellent stability under acidic (HCOOH), basic (NH3·H2O) and oxidative (H2O2) conditions, but reacts with β-ME, DTT and lysine which suggested that compound 3B may interact with cysteine or lysine residues. Moreover, molecular docking disclosed that compound 3B binds to the allosteric site of the GAC tetramer containing Arg317-Lys320-Leu321-Phe322-Tyr394-Glu325, which helped to rationalize the SAR and further design and optimization. Taken together, compound 3B could be used as a starting point for the development of new KGA inhibitors. 相似文献