Heteroatom Chemistry最新文献

A series of 2,3-dihydro-1,5-benzodiazepine derivatives have been synthesized and characterized using IR, NMR, GC-MS, single crystal XRD, and microanalysis. The results of their antibacterial activity against methicillin-resistance Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Bacillus subtilis, Streptococcus mutans, Pseudomonas aeruginosa, Salmonella typhi, and Streptococcus pyrogens indicated that most of the compounds were bacteriostatic (0.125−4 mg/mL) and also exhibited good biofilm inhibition (0.21−72.69%). The compounds were found to be synergistic when used in combination with other antibiotics. The antiproliferative and cytotoxic effects were also investigated against PC-3 prostate cancer and RAW 264.7 macrophage cell lines, respectively, using the MTT assay. Apart from compounds 6 and 7, a good number of the compounds (1, 2, 3, 4, 5, and 8) were selectively toxic to the prostate cancer cells at 20 µM, whilst sparing the normal cells. Compound 3 demonstrated the highest antiprostate cancer effect by reducing the viability of PC-3 cells to (13.75%), which was followed by compounds 1 (47.72%), 2 (48.18%), 4 (62.61%), 5 (66.70%), and 8 (69.55%).

Eleven conjugates between dihydroartemisinin (DHA) with thiols containing both ether and thioether bonds were designed, synthesized by a two-step procedure including etherification and S-alkylation. Analysis of the NMR spectral data indicated that the dimer of DHA with thiols 6-mercaptopurine and 2-mercaptoimidazole was produced with yields of 31% and 62%, respectively. Furthermore, the tautomerization of thiol 5-methoxy-2-mercaptobenzimidazole led to the formation of a mixture of two isomers in which they might be interchangeable through a dynamic tautomeric equilibrium in the solution. Screening in vitro biological activities revealed that most of the synthesized conjugates showed good cytotoxic and anti-inflammatory activity, while three of them displayed α-glucosidase inhibitory activity. Notably, two conjugates 5d and 5e of DHA with thiols 2-mercaptopyrimidine and 2-mercaptobenzothiazole had an effect in all tested activities in which conjugate 5e is the most potent.

An unsymmetrical salen-type Schiff base ligand, (Z)-1-(((2-((E)-(2-hydroxy-6-methoxybenzylidene)amino)phenyl)amino)methylene)naphthalen-2(1H)-one, and its Zn(II), Cu(II), Co(II), Mn(II), and Fe(III) complexes were synthesized and characterized by mass (MS), nuclear magnetic resonance (NMR), infrared (IR), ultraviolet-visible (UV-Vis) spectra, and effective magnetic moments. The thermal analyses of the obtained ligand and metal complexes were conducted by thermogravimetric analysis (TGA). Antimicrobial activity of the unsymmetrical Schiff base ligand and its metal complexes were examined for Staphylococcus aureus as Gram-positive bacteria and Escherichia coli as Gram-negative bacteria. In vitro anticancer property of synthetic compounds was estimated against human cancer cell lines, a subline of Hela tumor cell line (KB), and a human liver cancer cell line (HepG-2) as well.

A library of six compounds with new hybrids in a single molecule triazole ring attached to the phosphonium salts was synthesized. Click chemistry was, however, used to synthesize the 1-, 2-, and 3-triazole intermediates as a tether for the hybrid phosphonium salts. Their antibacterial activity against Gram-positive bacteria (Staphylococcus aureus and Enterococcus faecalis), Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa), and Mycobacterium smegmatis mc²155 was determined using the HT-SPOTi assay. Compound 2 showed the most effective antimicrobial activity as it inhibited the growth of Pseudomonas aeruginosa and Staphylococcus aureus at 0.0125 µg/mL and 31.25 µg/mL, respectively. From the FICI data, compounds 2ET-TOL (2) and RABYL-TOL (4) successfully modulated the activities of amoxicillin against Pseudomonas aeruginosa and Staphylococcus aureus. All the test compounds exhibited a concentration-dependent biofilm formation inhibition against S. aureus, except P-Z (compound 6). Compounds P-MEOXY (1) and 2ET-TOL (2) exhibited mild activity against P. aeruginosa with compound 4 showing antimycobacterial activity at 500 µg/mL.

Fifteen new pyrazole-4-carboxylic oxime ester derivatives were conveniently synthesized, and their structures were confirmed by ¹H NMR, ¹³C NMR, HRMS, and X-ray diffraction. Antifungal assays indicated that some of these compounds possessed good activity against S. sclerotiorum, B. cinerea, R. solani, P. oryae, and P. piricola at 50 ppm. Structure-activity relationships (SAR) were studied by molecular docking simulation.

Two isopropyl (3-methyl-1-oxo-1-((1-((4-(prop-2-yn-1-yloxy)phenyl)thio)propan-2-yl)amino)butan-2-yl)carbamate diastereomers were isolated. Fungicidal activities indicated that the isolated four chiral compounds possessed excellent activity against P. capsici with the EC₅₀ value of 4a (1.30 μg/mL), 4b (0.078 μg/mL), 4c (1.85 μg/mL), and 4d (44.4 μg/mL). Among them, compound 4b exhibited remarkably high activities against Phytophthora capsici, which is better than that of positive control dimethomorph. Its R and S isomers showed that chiral influences the activity against P. capsici.

In the last few years, nonsteroidal aromatase inhibitors (AIs) have been emerged as promising agents for treating hormone-dependent breast cancer in postmenopausal women because of their inhibitory effect on estrogen synthesis. Indeed, these compounds can block the activity of aromatase, the enzyme that intervenes in the last steps of estrogen production pathway. Triazoles are the core structures of nonsteroidal AIs. The nitrogen atom of the triazole moiety plays a fundamental role in the aromatase functionality by interacting with the iron ions of the heme group. In general, AIs possess numerous advantages as they quench the last step of estrogen synthesis without any inhibitory effects on the production of other steroids produced via the same pathway. Some AIs as anastrozole, letrozole, and vorozole have already been approved by the Food and Drug Administration in the treatment of breast cancer. The previously mentioned compounds present severe and adverse effects as polycystic ovary syndrome (PCOS), resistance onset on long-term treatments, and a higher risk of bone fractures. This review focuses intensively on the role of AIs in the treatment of hormone-sensitive types of cancers, especially the role of triazoles as nonsteroidal AIs. Also, the review provides an overview about the chemistry of triazoles along with the different methods by which the v-triazoles and s-triazoles are synthesized.

Chronic Hepatitis C is a global health threat and a silent killer. Regardless of the profound progress in preventing and treating this disease, research continues to discover new direct antiviral agents (DAAs), especially against novel targets. Our research has been directed to leverage the NS4A binding site to develop peptidomimetic inhibitors of the hepatitis C virus (HCV) NS3 protease. In previous reports, we could provide evidence of tunability of this site by peptide and nonpeptide NS3/4A inhibitors. In this report, we used structure-based techniques to design 1,2,3,4-tetrahydro-1,7-naphthyridine derivative as NS4A core mimics that cover the region between residues Ile-25′ to Arg-28′. The synthetic plan featured the Povarov reaction as an efficient strategy to construct the 1,7-naphthyridine core. Although this reaction has been reported in many literatures, critical assessments for its scope and limitations are scarce. In our work, we found that Povarov was extremely sensitive to alkene and aldehyde reactants. Moreover, using pyridine amines was not as successful as anilines. The most striking results were the lack of stability of compounds during purification and storage. The four compounds that survived the stability problems (1a-1d) did not show significant binding potency with NS3, because their structures were too simple to resemble the originally planned compounds.

The reductive cyclization of arenetellurols carrying α,β-unsaturated amide functionalities in the ortho position was investigated. Conceptually, such compounds can form 1,3-tellurazoles without the involvement of the unsaturation in the ring closure, they can form 1,4-tellurazinone derivatives, or they can undergo ring closure to 1,5-tellurazepinones. Amides derived from acrylic and methacrylic acid generated 1,5-tellurazepinones while 2-cinnamylamidobenzenetellurol cyclized to a 1,3-tellurazole derivative. In contrast, the reaction of acetylenedicarboxylic acid and its derivatives with 2-aminoarenetellurols generated 1,4-tellurazepinones, including a derivative of novel tricyclic naphtho [1, 4]tellurazinone. A comparison with analogous reactions of sulfur congeners indicates that their chemistry is a good predictor for the products obtained from 2-aminoarenetellurols. Selected compounds were characterized by X-ray crystallography. The present work offers access to previously unexplored organotellurium heterocycles.

Tandem conjugate addition–alkylation reaction of various amines with α-bromo-α, β-unsaturated ketones resulted in near-quantitative conversions into the corresponding aziridines when the reaction was carried out in the presence of 10 mol% of phase-transfer, PT catalysts in water. Some chiral quaternary ammonium salts derived from Cinchona alkaloids were investigated as water-stable PT catalysts. The scope and limitations of the reaction have also been investigated. The catalytic performances were significantly improved in comparison with the corresponding ordinary quaternary ammonium salt catalysts, and excellent yields (81%–96%) were obtained. Although an increase in the rate of aziridination has been accomplished, no stereoselectivity was observed. The positive values of the protocol have been confirmed.