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2.
Org Biomol Chem ; 21(45): 9037-9048, 2023 Nov 22.
Article in English | MEDLINE | ID: mdl-37933527

ABSTRACT

A novel C-N coupling of various arylamines with dialkyl azodicarboxylates under metal-free conditions for the rapid assembly of carbamates has been achieved. This established protocol features mild reaction conditions, simple operation, broad substrate scope, moderate to excellent yields and good tolerance of functional groups. Moreover, the potential synthetic utility of products was exemplified by a series of intriguing chemical operations.

3.
Cell Death Discov ; 9(1): 329, 2023 Sep 02.
Article in English | MEDLINE | ID: mdl-37660095

ABSTRACT

RNA binding proteins have the critical role in renal cell carcinoma (RCC) progression. However, the role of RBM47 in RCC has not been elucidated. In this study, we found that RBM47 was downregulated in RCC tissues and its expression was negatively correlated with the prognosis of RCC patients. Also, we found that the expression of RBM47 was regulated by CBP/P300-mediated H3K27ac in RCC. Functionally, RBM47 restrained RCC cells proliferation and metastasis. Mechanistically, RBM47 interfered with the interaction between HOXB-AS1 and p53 proteins via directly binding with HOXB-AS1, finally promoted the entry of p53 into the nucleus and therefore activated the p53 signaling. Moreover, RBM47 had a synergistic anticancer effect with sunitinib both in vivo and in vitro.

4.
ACS Omega ; 7(42): 38084-38093, 2022 Oct 25.
Article in English | MEDLINE | ID: mdl-36312435

ABSTRACT

A highly chemoselective reaction between α,ß-unsaturated trifluoromethyl ketones with azaarenes under metal-free conditions was carried out, affording a range of valuable azaarene-equipped CF3-tertiary alcohols in moderate to excellent yields (up to 95% yield) with good tolerance of functional groups, and their structures were confirmed by NMR, HRMS, and X-ray diffraction for validation. This method features simple reaction conditions (only solvent), high atom- and step-economy, and broad substrate scope. Moreover, most of the target products exhibited promising fungicidal activities, and compound 3al exhibited 91.65% fungicidal activity against R. solani, with an EC50 value of 0.18 mg/mL.

5.
Molecules ; 27(20)2022 Oct 13.
Article in English | MEDLINE | ID: mdl-36296452

ABSTRACT

A series of novel indole Schiff base derivatives (2a-2t) containing a 1,3,4-thiadiazole scaffold modified with a thioether group were synthesized, and their structures were confirmed using FT-IR, 1H NMR, 13C NMR, and HR-MS. In addition, the antifungal activity of synthesized indole derivatives was investigated against Fusarium graminearum (F. graminearum), Fusarium oxysporum (F. oxysporum), Fusariummoniliforme (F.moniliforme), Curvularia lunata (C. lunata), and Phytophthora parasitica var. nicotiana (P. p. var. nicotianae) using the mycelium growth rate method. Among the synthesized indole derivatives, compound 2j showed the highest inhibition rates of 100%, 95.7%, 89%, and 76.5% at a concentration of 500 µg/mL against F. graminearum, F. oxysporum, F.moniliforme, and P. p. var. nicotianae, respectively. Similarly, compounds 2j and 2q exhibited higher inhibition rates of 81.9% and 83.7% at a concentration of 500 µg/mL against C. lunata. In addition, compound 2j has been recognized as a potential compound for further investigation in the field of fungicides.


Subject(s)
Fungicides, Industrial , Fusarium , Antifungal Agents/chemistry , Fungicides, Industrial/chemistry , Schiff Bases/pharmacology , Spectroscopy, Fourier Transform Infrared , Indoles/pharmacology , Sulfides
6.
Molecules ; 28(1)2022 Dec 28.
Article in English | MEDLINE | ID: mdl-36615454

ABSTRACT

A new method for the synthesis of α-trifluoromethylated tertiary alcohols bearing coumarins is described. The reaction of 3-(trifluoroacetyl)coumarin and pyrrole provided the target compounds with high yields under catalyst-free, mild conditions. The crystal structure of compound 3fa was investigated by X-ray diffraction analysis. The biological activities, such as in vitro antifungal activity of the α-trifluoromethylated tertiary alcohols against Fusarium graminearum, Fusarium oxysporum, Fusarium moniliforme, Rhizoctonia solani Kuhn, and Phytophthora parasitica var nicotianae, were investigated. The bioassay results indicated that compounds 3ad, 3gd, and 3hd showed broad-spectrum antifungal activity in vitro. Compound 3cd exhibited excellent fungicidal activity against Rhizoctonia solani Kuhn, with an EC50 value of 10.9 µg/mL, which was comparable to that of commercial fungicidal triadimefon (EC50 = 6.1 µg/mL). Furthermore, molecular docking study suggested that 3cd had high binding affinities with 1W9U, like argifin.


Subject(s)
Fungicides, Industrial , Fusarium , Phytophthora , Antifungal Agents/chemistry , Structure-Activity Relationship , Molecular Docking Simulation , Rhizoctonia , Fungicides, Industrial/pharmacology , Coumarins/pharmacology , Coumarins/chemistry
7.
RSC Adv ; 10(24): 13929-13935, 2020 Apr 06.
Article in English | MEDLINE | ID: mdl-35498470

ABSTRACT

A highly efficient Friedel-Crafts alkylation of indole derivatives with ß-(trifluoroacetyl)coumarins using Sc(OTf)3 as a catalyst has been developed, which gives regioselective 1,2-adducts to afford 1-(ß-coumarinyl)-1-(ß-indolyl)trifluoroethanols. A series of tertiary trifluoroethanols containing different indole and coumarin groups were synthesized in moderate to excellent yields (up to 95%) in the presence of 5 mol% catalyst in a short time (only 2 minutes at least). A mechanism of the reaction, in which the trace amount of water plays the role of proton transfer in catalyzing circulation was proposed and confirmed.

8.
J Org Chem ; 77(1): 704-6, 2012 Jan 06.
Article in English | MEDLINE | ID: mdl-22098172

ABSTRACT

A facile convergent synthesis of the tricyclic core 2 of roseophilin is described, which represents the shortest route so far for the formal synthesis of roseophilin. The key step was a tandem pyrrole acylation-Nazarov cyclization reaction to form the cyclopenta[b]pyrrole moiety 4.


Subject(s)
Pyrroles/chemical synthesis , Catalysis , Cyclization , Heterocyclic Compounds, 3-Ring/chemical synthesis , Heterocyclic Compounds, 3-Ring/chemistry , Molecular Structure , Pyrroles/chemistry , Stereoisomerism
9.
Bioorg Med Chem Lett ; 21(22): 6770-2, 2011 Nov 15.
Article in English | MEDLINE | ID: mdl-21974951

ABSTRACT

Three novel 4-subsituted-7-(2'-deoxy-2'-fluoro-4'-azido-ß-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine analogues were designed, synthesized, and tested for their anti-HIV-1 activity. Initial biological studies indicated that among these pyrrolo[2,3-d]pyrimidine ribonucleoside analogues, 4-amino-7-(2'-deoxy-2'-fluoro-4'-azido-ß-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine 10 exhibited the most potent anti-HIV-1 activity (EC(50)=0.5±0.3 µM), while 4-hydroxy-7-(2'-deoxy-2'-fluoro-4'-azido-ß-D-ribofuranosyl)pyrrolo[2,3-d] pyrimidine 9 and 4-amino-5-fluoro-7-(2'-deoxy-2'-fluoro-4'-azido-ß-D-ribofuranosyl)pyrrolo[2,3-d] pyrimidine 11 showed moderate activity (EC(50)=13±8 and 5.4±0.3 µM, respectively). The cytotoxicity of these compounds has also been assessed. No significant cytotoxicities were found for any of these compounds with concentrations up to 25 µM.


Subject(s)
Anti-HIV Agents/chemistry , Anti-HIV Agents/pharmacology , HIV-1/drug effects , Pyrimidines/chemistry , Pyrimidines/pharmacology , Ribonucleosides/chemistry , Ribonucleosides/pharmacology , Anti-HIV Agents/chemical synthesis , HIV Infections/drug therapy , Humans , Pyrimidines/chemical synthesis , Pyrroles/chemical synthesis , Pyrroles/chemistry , Pyrroles/pharmacology , Ribonucleosides/chemical synthesis
10.
Eur J Med Chem ; 46(9): 4178-83, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21745701

ABSTRACT

We prepared 1-(4'-azido-2'-deoxy-2'-fluoro-ß-D-arabinofuranosyl)cytosine (10) and its hydrochloride salt (11) as potential antiviral agents based on the favorable antiviral profiles of 4'-substituted nucleosides. Compounds 10 and 11 were synthesized from 1,3,5-O-tribenzoyl-2-deoxy-2-fluoro-D-arabinofuranoside in multiple steps, and their structures were unequivocally established by IR, (1)H NMR, (13)C NMR, and (19)F NMR spectroscopy, HRMS, and X-ray crystallography. Compounds 10 and 11 exhibited potent anti-HIV-1 activity (EC(50): 0.3 and 0.13 nM, respectively) without significant cytotoxicity in concentrations up to 100 µM. Compound 11 exhibited extremely potent anti-HIV activity against NL4-3 (wild-type), NL4-3 (K101E), and RTMDR viral strains, with EC(50) values of 0.086, 0.15, and 0.11 nM, respectively. Due to the high potency of 11, it was also screened against an NIH Reagent Program NRTI-resistant virus panel containing eleven mutated viral strains and for cytotoxicity against six different human cell lines. The results of this screening indicated that 11 is a novel NRTI that could be developed as an anti-AIDS clinical trial candidate to overcome drug-resistance issues.


Subject(s)
Anti-HIV Agents/chemical synthesis , Anti-HIV Agents/pharmacology , Cytarabine/chemistry , Nucleosides/chemical synthesis , Nucleosides/pharmacology , Anti-HIV Agents/chemistry , Cell Line , Crystallography, X-Ray , Humans , Inhibitory Concentration 50 , Magnetic Resonance Spectroscopy , Mass Spectrometry , Models, Molecular , Nucleosides/chemistry , Spectrophotometry, Infrared
11.
Biochem Pharmacol ; 81(7): 848-55, 2011 Apr 01.
Article in English | MEDLINE | ID: mdl-21219886

ABSTRACT

Inhibition of cellular DNA synthesis is a strategy to block cancer cell division. Nucleoside analogues can incorporate into DNA and terminate DNA strand elongation. So far, several nucleoside analogues have been successfully used as anticancer drugs. FNC, 2'-deoxy-2'-ß-fluoro-4'-azidocytidine is a novel cytidine analogue which demonstrated potent activity against hepatitis C virus (HCV). To investigate the therapeutic potential of FNC in human cancers we studied its activity in a number of cancer cells in vitro and in vivo. FNC potently inhibited cell proliferation with an IC(50) of 0.95-4.55µM in a variety of aggressive human cancer cell lines including B-cell non-Hodgkin's lymphomas, lung adenocarcinoma and acute myeloid leukemia. Cells treated with FNC exhibited G1 and S cell cycle arrest at high and low dose, respectively, which confirms the mechanism of action of nucleoside analogues. Treatment of B-NHL cell lines with FNC induced apoptosis in a dose and time dependent manner. Finally, mouse xenograft models of hepatocarcinoma (H22), sarcoma (S180) and gastric carcinoma (SGC7901) demonstrated that FNC had significant tumor growth inhibition activity in a dose-dependent manner with low toxicity. Together, our results suggest that FNC may be a valuable therapy in cancer patients and warrant early phase clinical trial evaluation.


Subject(s)
Antineoplastic Agents/pharmacology , Azides/pharmacology , Cell Proliferation/drug effects , Deoxycytidine/analogs & derivatives , Animals , Cell Cycle , Cell Line, Tumor , Deoxycytidine/pharmacology , Humans , Inhibitory Concentration 50 , Mice
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