Subplenones A-J: Dimeric Xanthones with Antibacterial Activity from the Endophytic Fungus sp. CPCC 401465.

Subplenones A-J (-), 10 new xanthone dimers, have been isolated and characterized from the endophytic fungus sp. CPCC 401465, which resides within the Chinese medicinal plant . The isolation process was guided by antibacterial assays and molecular-networking-based analyses.

Design, synthesis, and anti-influenza A virus activity evaluation of novel indole containing derivatives of triazole.

We designed and synthesized 18 substituted indole derivatives containing a triazole scaffold as novel anti-influenza A virus candidates using a bio-isosteric and scaffold-hopping strategy from the lead compound 4-32-2. Most of the target compounds (eg: 6, 7a, 7d, 7f-j, 7l, 7m, 7o, 7q) exhibited potent anti-influenza A virus activity and low cytotoxicity in vitro. In particular, 7a exhibited the most potent anti-IAV activity (IC: 1.

Discovery of 1,8-naphthalidine derivatives as potent anti-hepatic fibrosis agents via repressing PI3K/AKT/Smad and JAK2/STAT3 pathways.

Liver fibrosis is one of the most common pathological consequences of chronic liver diseases (CLD). To develop effective antifibrotic strategies, a novel class of 1-(substituted phenyl)-1,8-naphthalidine-3-carboxamide derivatives were designed and synthesized. By means of the collagen type I α 1 (COL1A1)-based screening and cytotoxicity assay in human hepatic stellate cell (HSC) line LX-2, seven compounds were screened out from total 60 derivatives with high inhibitory effect and relatively low cytotoxicity for further COL1A1 mRNA expression analysis.

Design, synthesis, and antibacterial evaluation of PFK-158 derivatives as potent agents against drug-resistant bacteria.

Infections caused by antibiotic resistant bacteria are a major health concern throughout the world. It is well known that PFK-158 can enhance the antibacterial effect of polymyxin, but its own anti-bactericidal effect is rarely discussed. In order to investigate the anti-bactericidal effect of PFK-158 and its derivatives, PFK-158 and 35 derivatives were designed, synthesized, and evaluated for their antibacterial activities.

Design, synthesis and biological evaluation of HIV-1 protease inhibitors with morpholine derivatives as P2 ligands in combination with cyclopropyl as P1' ligand.

A series of novel HIV-1 protease inhibitors has been designed and synthesized, which contained morpholine derivatives as the P2 ligands and hydrophobic cyclopropyl as the P1' ligand at the meantime in this study, with the aim of improving the interactions between the active sites of HIV-1 protease and the inhibitors. Twenty-eight compounds were synthesized and assessed, among which inhibitors m18 and m1 exhibited excellent inhibitory effect on the activity of HIV-1 protease with IC value of 47 nM and 53 nM, respectively. The molecular modeling of m1 revealed possible hydrogen bondings or van der Waals between the inhibitor and the protease, worthy of in-depth study.

Design, synthesis, and biological activity evaluation of a series of pleuromutilin derivatives with novel C14 side chains.

In this work, according to the 'me-too me-better' design strategy, a peculiar side chain different from lefamulin at C14 position of pleuromutilin was introduced. A series of novel thioether pleuromutilin derivatives containing cyclohexane in the C14 chain was synthesized by ten-step synthesis reaction. All derivatives were characterized by Nuclear Magnetic Resonance (NMR) and High Resolution Mass Spectrometer (HRMS).

A novel biphenyl compound IMB-S7 ameliorates hepatic fibrosis in BDL rats by suppressing Sp1-mediated integrin αv expression.

Chronic tissue injury with fibrosis results in the disruption of tissue architecture, organ dysfunction, and eventual organ failure. Therefore, the development of effective antifibrotic drugs is urgently required. IMB-S7 is novel biphenyl compound derived from bifendate (biphenyldicarboxylate) that is used for the treatment of chronic hepatitis in China.

Synthesis and biological evaluation of new HIV-1 protease inhibitors with purine bases as P2-ligands.

Introducing purine bases to P2-ligands might enhance the potency of Human Immunodeficiency Virus-1 (HIV-1) protease inhibitory because of the carbonyl and NH groups promoting the formation of extensive H-bonding interactions. In this work, thirty-three compounds are synthesized and evaluated, among which inhibitors 16a, 16f and 16j containing N-2-(6-substituted-9H-purin-9-yl)acetamide as the P2-ligands along with 4-methoxylphenylsulfonamide as the P2'-ligand, display potent inhibitory effect on the activity of HIV-1 protease with IC 43 nM, 42 nM and 68 nM in vitro, respectively.

Design, synthesis and biological evaluation of novel HIV-1 protease inhibitors with pentacyclic triterpenoids as P2-ligands.

The design, synthesis and SAR study of a new series of HIV-1 protease inhibitors with pentacyclic triterpenoids as P2 ligands and phenylsulfonamide as P2' ligands were discussed. These compounds exhibited micromolar inhibitory potency, among which compound T1c displayed HIV-1 protease inhibition with IC values of 0.12 μM, which was 67 times the inhibitory activity of its raw material Ursolic acid (8.

A novel ASBT inhibitor, IMB17-15, repressed nonalcoholic fatty liver disease development in high-fat diet-fed Syrian golden hamsters.

The manipulation of bile acid (BA) homeostasis by blocking the ileal apical Na-dependent bile salt transporter (ASBT/SLC10A2) may have therapeutic effects in nonalcoholic fatty liver disease. We developed a novel ASBT inhibitor, an N-(3,4-o-dichlorophenyl)-2-(3-trifluoromethoxy) benzamide derivative referred to as IMB17-15, and investigated its therapeutic effects and the molecular mechanisms underlying the effects. Syrian golden hamsters were challenged with high-fat diet (HFD) to induce NAFLD and were subsequently administered 400 mg/kg IMB17-15 by gavage daily for 21 days.

Antibacterial Activity and Structure-Activity Relationship of a Series of Newly Synthesized Pleuromutilin Derivatives.

A series of novel thioether or sulfoxide-type pleuromutilin derivatives containing heteroaromatic substituents at the end of C14 side chain were designed and synthesized. All of the derivatives were evaluated for their in vitro antibacterial activity. Some of them showed good to excellent antibacterial activity comparable to retapamulin and azamulin in most of the tested Gram-positive pathogens.

A novel protein kinase inhibitor IMB-YH-8 with anti-tuberculosis activity.

Protein kinase B (PknB) is one of the Mycobacterium tuberculosis serine/threonine protein kinases and has an essential role in sustaining mycobacterial growth. Here, we identified and characterized a novel small molecule compound named IMB-YH-8 that inhibited PknB and served as anti-mycobacteria lead compound. IMB-YH-8 inhibited PknB auto-phosphorylation and the phosphorylation of GarA by PknB in a dose-dependent manner.

[Advances in studies of ileal apical sodium-dependent bile acid transporter].

Bile acids play critical roles in the regulation of metabolism and absorption of lipids. The ileal apical sodium-dependent bile acid transporter (ASBT) located at the enterocyte brush border is responsible for the reuptake of bile acids and the maintenance of bile acid homeostasis. Recently, a number of investigations have been made concerning the regulation and control of ASBT and the relationship between ASBT and intestinal inflammation, tumorigenesis, diabetes mellitus and hyperlipemia, which suggests ASBT as a potential therapeutic target of these diseases.

Herbihabitans rhizosphaerae gen. nov., sp. nov., a member of the family Pseudonocardiaceae isolated from rhizosphere soil of the herb Limonium sinense (Girard).

The taxonomic position of an actinobacterium, designated CPCC 204279T, which was isolated from a rhizosphere soil sample of the herb Limonium sinense collected from Xinjiang Province, China, was established using a polyphasic approach. Whole-cell hydrolysates of strain CPCC 204279T contained galactose and arabinose as diagnostic sugars and meso-diaminopimelic acid as the diamino acid. The muramic acid residues in the peptidoglycan were N-acetylated.

[Impurity analysis and quality evaluation for commercial levofloxacin formulations using LC-MS/MS method].

The study aims to develop a rapid, specific and sensitive method for quantitative analysis of trace impurities in levofloxacin formulation using LC-MS/MS. The quality of the different formulations from 19 plants was evaluated in the contents of the impurities. The results indicated that there were 5 impurities in the samples, and the content was different in the products with same formulation by different plants.

[Establishment and application of a high-throughput drug screening model based on COL1A1 promoter for anti-liver fibrosis].

For screening the potential drugs as anti-liver fibrosis candidates, we established a high- throughput drug screening cell model based on COL1A1 promoter. The activity of COL1A1 promoter and luciferase reporter gene can be elevated by TGF-β1, and inhibited by candidate drugs. We constructed a recombined plasmid with COL1A1 promoter and luciferase reporter gene pGL4.

Synthesis and biological evaluation of novel HIV-1 protease inhibitors using tertiary amine as P2-ligands.

A series of tertiary amine derivatives exhibiting potent HIV-1 protease inhibiting properties were identified. These novel inhibitors were designed based on the structure of Darunavir with modification on the P2 and P2' position. This effort led to discovery of 35e and 38e, which exhibited excellent HIV-1 protease inhibition with IC50 values of 15 nM and 64 nM, respectively.

Crystal structure of ethyl 4-[(1H-pyrazol-1-yl)meth-yl]benzoate.

In the title mol-ecule, C13H14N2O2, the dihedral angle between the pyrazole and benzene ring mean planes is 76.06 (11)°, and the conformation of the ethyl side chain is anti [C-O-C-C = -175.4 (3)°].

Synthesis and cytotoxic evaluation of alkoxylated chalcones.

A series of chalcones a1-20 bearing a 4-OMe groups on the A-ring were initially synthesized and their anticancer activities towards HepG2 cells evaluated. Subsequently, a series of chalcones b1-42 bearing methoxy groups at the 2' and 6'-positions of the B-ring were synthesized and their anticancer activities towards five human cancer cell lines (HepG2, HeLa, MCF-7, A549 and SW1990) and two non-tumoral human cell lines evaluated. The results showed that six compounds (b6, b8, b11, b16, b18, b22, b23 and b29) displayed promising activities, with compounds b22 and b29 in particular showing higher levels of activity than etoposide against all five cancer cell lines.

Di-tert-butyl 1-[2-hy-droxy-3-(methyl-sulfan-yl)prop-yl]hydrazine-1,2-di-carboxyl-ate.

The title compound, C14H28N2O5S, was synthesized by the reaction of 2-[(methyl-sulfan-yl)meth-yl]oxirane with di-tert-butyl oxalate in hydrazine hydrate. In the crystal, mol-ecules are linked by N-H⋯O and O-H⋯O hydrogen bonds into supra-molecular chains propagating along the b-axis direction.

tert-Butyl N-[2-(N-isobutyl-4-meth-oxy-benzene-sulfonamido)-eth-yl]carbamate.

The title compound, C18H30N2O5S, was synthesized by the reaction of tert-butyl 2-(iso-butyl-amino)-ethyl-carbamate with p-meth-oxy-phenyl-sulfonyl chloride. In the mol-ecule, two intra-molecular C-H⋯O hydrogen bonds are observed. In the crystal, mol-ecules are linked by N-H⋯O hydrogen bonds involving the imino group N atom and the ester group O atom into chains running parallel to the b axis.

An integrated approach for detection and characterization of the trace impurities in levofloxacin using liquid chromatography-tandem mass spectrometry.

Rationale: Impurity analysis plays an important role to guarantee the quality and safety of pharmaceuticals. However, identification of impurities remains challenging, especially for those unknown or at trace levels. We present an integrated approach to detect and characterize the trace impurities in drugs.

Arylsulfonylamino-benzanilides as inhibitors of the apical sodium-dependent bile salt transporter (SLC10A2).

The apical sodium-dependent bile salt transporter (ASBT) plays a pivotal role in maintaining bile acid homeostasis. Inhibition of ASBT would reduce bile acid pool size and lower cholesterol levels. In this report, a series of novel arylsulfonylaminobenzanilides were designed and synthesized as potential inhibitors of ASBT.

Design, synthesis and anticancer activity of 1-acyl-3-amino-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole derivatives.

A series of novel 1-acyl-3-amino-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole derivatives were designed and synthesized. These derivatives were initially evaluated for their in vitro anticancer activity against human colon carcinoma HCT-116 cell line, and compounds 11a, b were chosen for further evaluation their in vitro activity against other five human cancer cell lines. These results indicate that most of the target compounds have considerable in vitro anticancer activity.

N-(1-Acetyl-5-benzoyl-1,4,5,6-tetra-hydro-pyrrolo-[3,4-c]pyrazol-3-yl)benzamide.

In the mol-ecule of the title compound, C(21)H(18)N(4)O(3), the fused pyrrolo-[3,4-c]pyrazole ring system is approximately planar [maximum deviation = 0.0486 (16) Å] and forms dihedral angles of 87.21 (8) and 35.