Solvent-Free Synthesis of Pyrimidine Nucleoside-Aminophosphonate Hybrids and Their Biological Activity Evaluation

A novel and highly efficient one-pot three-component synthesis of α-aminophosphonates under neat condition was developed. By employing this method, hybrid compounds of aminophosphonate with pyrimidine nucleosides were synthesized in good to excellent yields starting from 5-formyl-2′-deoxyuridine, aniline and dimethyl phosphite. The antiviral and antileishmanial activities of these novel hybrid compounds were also studied but none were found to be active.     

Synthesis of Novel Chalcone-Based L-Homoserine Lactones and Their Quorum Sensing Inhibitory Activity Evaluation

Russian Journal of Bioorganic Chemistry - Two novel series of chalcone-based homoserine lactones were synthesized and their quorum sensing (QS) inhibitory activity was evaluated against Pseudomonas...     

微生物糖基转移酶催化合成槲皮素糖苷及其抗炎活性评价

利用微生物来源的糖基转移酶GT-1、GT-2和BTGT-1对槲皮素进行糖基化修饰。研究发现这3种酶均能够催化以槲皮素和UDP-葡萄糖为底物生成槲皮素-3-O-β-D-葡萄糖（异槲皮苷）,GT-1、 GT-2和BTGT-1催化反应的产物生成率分别为5.33%、15.18%和63.82%。通过对槲皮素、异槲皮苷和槲皮素-N-乙酰-D-氨基葡萄糖进行水溶性以及体外细胞抗炎活性检测,发现槲皮素经糖基化后其水溶性得到较大提高,异槲皮苷和槲皮素-N-乙酰-D-氨基葡萄糖水溶性分别是槲皮素的13.8倍和15.4倍。同等浓度下槲皮素糖苷对RAW264.7 细胞的毒性作用低于槲皮素,且3种化合物在一定浓度范围内对LPS诱导RAW264.7细胞释放NO、 IL-1β、IL-6 都有显著的抑制作用,且呈剂量依赖性,研究表明3种化合物都具有一定的抗炎作用。     

Synthesis of Novel Carbocyclic Nucleosides with a Modified Cyclopentane Ring and Evaluation of Their Antiviral Activity

Abstract

New carbocyclic nucleosides with purine (compounds 2a-2c), 8-azapurine (compounds 2d and 2e) or pyrimidine (compound 3) as base were prepared and assayed for in vitro activity.     

Synthesis and Antitumor Activity Evaluation of Novel 2-Amino-5-Ethylpyrimidine Derivatives

Russian Journal of Bioorganic Chemistry - In order to discover novel high efficiency and low toxic anticancer drugs, a series of novel 2-amino-5-ethylpyrimidine derivatives (XIIa–x) were...     

Synthesis of Some Pyridine Ribosides and Their Biological Activity

Abstract

A synthesis of 1-(β-D-ribofuranosyl)-pyridin-2-thiones via reaction of 3-cyanopyridin-2(H)-thiones with 2,3,5-tri-O-benzoyl-D-ribofuranosyl bromide under basic conditions, followed by hydrolysis with methanolic ammonia is reported.     

Microbial Synthesis of Purine Arabinosides and Their Biological Activity

A simple method for the synthesis of various purine arabinosides from purine bases and uracil arabinoside by microbial transarabinosylation is described. A wet cell paste of Enterobacter aerogenes AJ 11125 showed a wide substrate specificity range for purine bases. Not only naturally occurring purine bases such as adenine and hypoxanthine but also unnatural bases such as 6-thioguanine and 2-chlorohypoxanthine were catalyzed to give the corresponding purine arabinosides. The enzymatically synthesized purine arabinosides were isolated from the reaction mixtures and identified by physicochemical means. The biological activities of the compounds were investigated and it was found that thioguanine arabinoside and 2-methyladenine arabinoside have potent activity against Hela cells, and their ED₅₀ were 10.5 and 21.5 μg/ml, respectively.     

Synthesis of Selenium-Containing Chitosan Derivatives and Their Antibacterial Activity

Applied Biochemistry and Microbiology - The interaction of chitosan with 3-(chloromethyl)-[1,2,4]selendiazole[4,5-a]pyridin-4 bromide results in water-soluble, selenium-containing, cationic...     

Synthesis of 2-Bromomethyl-3-Hydroxy-2-Hydroxymethyl-Propyl Pyrimidine and Theophylline Nucleosides Under Microwave Irradiation. Evaluation of Their Activity Against Hepatitis B Virus

Alkylation of 2-methylthiopyrimidin-4(1H)-one (1a) and its 5(6)-alkyl derivatives 1b–d as well as theophylline (7) with 2,2-bis(bromomethyl)-1,3-diacetoxypropane (2) under microwave irradia-tion gave the corresponding acyclonucleosides 1-[(3-acetoxy-2-acetoxymethyl-2-bromomethyl)prop-1-yl]-2-methyl-thio pyrmidin-4(1H)-ones 3a–d and 7-[(3-acetoxy-2-acetoxymethyl-2-bromomethyl)prop-1-yl]theophylline (8), which upon further irradiation gave the double-headed acyclonucleosides 1,1 ′-[(2,2-diacetoxymethyl)-1,3-propylidene]-bis[(2-(methylthio)-pyrimidin-4(1H)-ones] 4a–c, and 7,7 ′-[(2,2-diacetoxymethyl)-1,3-propylidene]-bis(theophylline) (9). The deacetylated derivatives were obtained by the action of sodium methoxide. The activity of deacetylated nucleosides against Hepatitis B virus was evaluated. Compound 5b showed moderate inhibition activity against HBV with mild cytotoxicity.     

Synthesis of Optically Active N-(2-Pyridyloxiran-2-ylmethyl) benzenesulfonamide Derivatives and Their Herbicidal Activity

Novel herbicidally active sulfonamide compounds having a 2-arylsubstituted oxiranylmethyl structure are racemates due to a chiral carbon in the oxirane moiety. To clarify the stereochemical structure-activity relationship, we synthesized each enantiomer of 4-chloro-N-[2-(6-chloropyridin-2-yl)-2-oxiran-2-ylmethyl]-3,N-dimethylbenzenesulfonamide and N-[2-(6-chloropyridin-2-yl)-2-oxiran-2-ylmethyl]-N-methyl-5,6,7,8-tetrahydronaphthalene-2-sulfonamide by chemical methods including Sharpless asymmetric chlorohydroxylation. The results of herbicidal tests indicated that the (S)-isomers were the active forms.     

Synthesis and Anti-Proliferation Activity Evaluation of Novel 2-Chloroquinazoline as Potential EGFR-TK Inhibitors

A novel series of 2-chloroquinazoline derivatives had been synthesized and their anti-proliferation activities against the four EGFR high-expressing cells A549, NCI-H1975, AGS and HepG2 cell lines were evaluated. The preliminary SAR study of the scaffold of new compounds showed that the compounds with a chlorine substituent on R³ had a better anti-proliferation activity than those substituted by hydrogen atom or vinyl group. Among them, 2-chloro-N-[2-chloro-4-(3-chloro-4-fluoroanilino)quinazolin-6-yl]acetamide (10b) had the best activity, and the corresponding IC₅₀ were 3.68, 10.06, 1.73 and 2.04 μM, respectively. And compound 10b had better or equivalent activity against four cell lines than Gefitinib. The activity of the compound 10b on the EGFR enzyme was subsequently tested. The Wound Healing of A549, AGS and HepG2 cells by this compound showed that the compound can inhibit the migration of cancer cells. Finally, the action channel of the compound 10b was supported by western blotting experiments. It provides useful information for the design of EGFR-TK inhibitors.     

Synthesis of New N-Benzoyl-N'-Triazine Thiourea Derivatives and Their Antibacterial Activity

Russian Journal of Bioorganic Chemistry - A series of new N-benzoyl-N'-triazine thiourea derivatives have been synthesized via the reaction of...     

Synthesis of Lipid Derivatives of Pyrrole Polyamide and Their Biological Activity

Novel fatty acyl and phospholipid derivatives of pyrrole polyamide were synthesized. Their cytotoxicity against a cancer cell line of MT-4 cells and those infected by human immunodeficiency virus (HIV) was examined. Although no anti-HIV activity was found, their cytotoxicitty against the cancer cells was significantly enhanced by introducing a lipophilic group into the pyrrole polyamide.     

A Bacteriophage Mediated Gold Nanoparticles Synthesis and Their Anti-biofilm Activity

In the present study, gold nanoparticles (AuNPs) synthesis was carried out by using a rare bacteriophage which is morphologically similar to 7–11 phages of the C3 morphotype of tailed phage belonging to Podoviridae family as green route. Effect of various physiological parameters like pH, temperature and concentration of gold chloride salt on AuNPs synthesis was studied. The reaction mixtures have shown vivid colours at various physiological parameters. Phage inspired AuNPs were further characterized by using different techniques such as UV–Vis spectrophotometry, scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD) and dynamic light scattering (DLS). DLS study revealed synthesis of various sizes of AuNPs in the range of 20–100 nm. SEM studies revealed synthesis of varied shaped AuNPs, viz., spheres, hexagons, triangles, rhomboids and rectangular etc. The presence of Au in the nanostructures was confirmed by EDS. The XRD pattern reflects the crystalline nature and nano size of AuNPs. These phage inspired AuNPs showed anti-bacterial activity against different bacterial pathogens. Anti-biofilm activity of AuNPs was evaluated on a glass slide. It was noticed that at 0.2 mM concentration of these AuNPs about 80% of biofilm formation by Pseudomonas aeruginosa, a human pathogen was inhibited. Thus, the phage inspired AuNPs synthesis could be potential therapeutic agents against human pathogens.     

Synthesis of Amido Sulfonamido Heteroaromatics Under Ultrasonication and Their Antimicrobial Activity

A convenient and facile methodology for N‐sulfonylation of heteroaryl amines with ethyl chlorosulfonylacetate in the presence of dispersed sodium in THF under ultrasonication is reported. The corresponding heteroaryl sulfonamido esters are directly condensed with heteroaryl amines to get amido sulfonamido heteroaromatics in the presence of a mild base in THF under ultrasonication. Utilization of easy reaction conditions, shorter reaction times, and isolation of products in high yields under ultrasonication make this process as economically viable. The compounds 12c , 12d , 12f and 13f are potential antibacterial agents against B. subtilis and the compounds 12f , 13c and 13f are potential antifungal agents against A. niger.     

Synthesis and Anticancer Activity Evaluation of Some Thienopyrimidine Derivatives

Russian Journal of Bioorganic Chemistry - The current study focused on effective and straightforward routes for preparing a new series of thieno[2,3-d]pyrimidine derivatives in addition to their...     

Fluorinated Carbaacyclonucleosides: Synthesis and Evaluation of Antiviral Activity

Abstract

Two series of fluoroacyclic nucleosides were synthesised by condensation of nucleic acid bases with substituted fluoropentanes. 1-(5′-Fluoro-4′-hydroxypentyl)-cytosine showed a modest activity against cytomegalovirus (MIC₅₀: 12–15 μg/ml). All the other compounds were inactive against all the viruses tested.     

Synthesis of New 4-Aminoquinolines and Evaluation of Their In Vitro Activity against Chloroquine-Sensitive and Chloroquine-Resistant Plasmodium falciparum

The efficacy of chloroquine, once the drug of choice in the fight against Plasmodium falciparum, is now severely limited due to widespread resistance. Amodiaquine is one of the most potent antimalarial 4-aminoquinolines known and remains effective against chloroquine-resistant parasites, but toxicity issues linked to a quinone-imine metabolite limit its clinical use. In search of new compounds able to retain the antimalarial activity of amodiaquine while circumventing quinone-imine metabolite toxicity, we have synthesized five 4-aminoquinolines that feature rings lacking hydroxyl groups in the side chain of the molecules and are thus incapable of generating toxic quinone-imines. The new compounds displayed high in vitro potency (low nanomolar IC₅₀), markedly superior to chloroquine and comparable to amodiaquine, against chloroquine-sensitive and chloroquine-resistant strains of P. falciparum, accompanied by low toxicity to L6 rat fibroblasts and MRC5 human lung cells, and metabolic stability comparable or higher than that of amodiaquine. Computational studies indicate a unique mode of binding of compound 4 to heme through the HOMO located on a biphenyl moeity, which may partly explain the high antiplasmodial activity observed for this compound.     

Synthesis of Quinoxlines Containing 1,2,3-Triazoles and Their Anti-Bacterial and Anti-Cancer Activity

Russian Journal of Bioorganic Chemistry - A series of 1-((1aryl)-1H-1,2,3-triazol-4-yl)methyl)quinoxalin-2(1H)-ones have been synthesized in moderate to high yields and evaluated for their...     

Synthesis and Biological Evaluation of 1,3,5-Trisubstituted 2-Pyrazolines as Novel Cyclooxygenase-2 Inhibitors with Antiproliferative Activity

A new series of 1,3,5-trisubstituted 2-pyrazolines for the inhibition of cyclooxygenase-2 (COX-2) were synthesized. The designed structures include a COX-2 pharmacophore SO₂CH₃ at the para-position of the phenyl ring located at C-5 of a pyrazoline scaffold. The synthesized compounds were tested for in vitro COX-1/COX-2 inhibition and cell toxicity against human colorectal adenocarcinoma cell lines HT-29. The lead compound (4-chlorophenyl){5-[4-(methanesulfonyl)phenyl]-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl}methanone ( 16 ) showed significant COX-2 inhibition (IC₅₀=0.05±0.01 μM), and antiproliferative activity (IC₅₀=5.46±4.71 μM). Molecular docking studies showed that new pyrazoline-based compounds interact via multiple hydrophobic and hydrogen-bond interactions with key binding site residues of the COX-2 enzyme.