[Effects of family dignity intervention on male infertility patients and their spouses].

OBJECTIVE: To investigate the effects of family dignity intervention (FDI) on anxiety, depression, hope level and quality of life (QOL) of male infertility patients and their spouses. METHODS: Using quasi-experimental design, we selected male infertility patients and their spouses undergoing human-assisted reproductive technology (ART) in our Center of Reproductive Medicine from June to December 2022 and divided them into an intervention group (38 couples) and a control group (40 couples). The former underwent a four-stage FDI, including ovulation promotion cycle assessment, family sharing, pre-transplantation interview and post-transplantation follow-up, while the latter received routine nursing. Using Hospital Anxiety and Depression Scale, Herth Hope Index and Fertility Quality of Life Scale, we evaluated the effects of FDI before and after transplantation. RESULTS: After FDI, the anxiety and depression scores were significantly lower (P < 0.05) and the total scores on the hope level and all other dimensions remarkably higher in the intervention group than in the control (P < 0.05). The self-confidence of the couples in the intervention groups in ART treatment was markedly increased in comparison with that of the controls, and their scores on physical and mental health were significantly higher than those of the latter (P < 0.05). CONCLUSION: FDI can effectively relieve the anxiety and depression, raise the hope level and improve the quality of life of both male infertility patients and their spouses.

Scocycamides, a Pair of Macrocyclic Dicaffeoylspermidines with Butyrylcholinesterase Inhibition and Antioxidation Activity from the Roots of Scopolia tangutica.

A pair of new macrocyclic spermidine alkaloids, (+)-(S)-scocycamide and (-)-(R)-scocycamide, were isolated from the roots of Scopolia tangutica. Their structures were established by extensive spectroscopic data, electronic circular dichroism analyses, and chemical synthesis. They featured a unique 6/18 fused bicyclic framework with spermidine and catechol units, representing a new subtype of natural spermidine alkaloids. A plausible biosynthetic pathway was also proposed. They inhibited butyrylcholinesterase and exhibited antioxidant capacity, suggesting beneficial constituents against Alzheimer's disease and oxidation.

Determination of nitrofuran metabolites in shrimp by high performance liquid chromatography with fluorescence detection and liquid chromatography-tandem mass spectrometry using a new derivatization reagent.

A high performance liquid chromatography with fluorescence detection (HPLC-FLD) method for the simultaneous determination of total nitrofuran metabolite residues (furazolidone, furaltadone, nitrofurantoin, and nitrofurazone) in shrimp was developed. The method involves the acid hydrolysis of protein-bound metabolites, followed by the derivatization of the freed metabolites with the new fluorescent derivatization reagent 2-hydroxy-1-naphthaldehyde (HN) and subsequent liquid-liquid extraction (LLE). Separation is achieved on a YMC-Pack Polymer C18 column under alkaline conditions, and the high fluorescence intensity of the derivatives at an emission wavelength Em=463nm (Ex=395nm) enables, for the first time, their simultaneous determination in shrimp at concentrations as low as 1µg/kg by HPLC-FLD. The method was validated using blank shrimp fortified with all four metabolites at 0.5, 1.0 and 2.0µg/kg. Recoveries were >87% with relative standard deviations of <8.1% for all four metabolites. Furthermore, the results obtained by HPLC-FLD were in very good agreement with those obtained by LC-MS/MS analysis.

High-performance liquid chromatography with fluorescence detection for the determination of nitrofuran metabolites in pork muscle.

A simple and sensitive HPLC method with fluorescence detection (HPLC-FLD) is reported for the simultaneous determination of metabolites of four nitrofuran drugs (furazolidone, furaltadone, nitrofurantoin and nitrofurazone) in pork muscle. The method involves acid hydrolysis of the protein-bound drug metabolites and the conjugation of the released side-chains with a novel fluorescence agent 2-hydroxy-1-naphthaldehyde. After liquid-liquid extraction and effective separation of the derivatives on a YMC-Pack Polymer C18 column at 40°C under alkaline conditions, the high fluorescence intensity of these derivatives at emission wavelength λem = 463 nm enables their simultaneous determination in pork muscle at concentrations as low as 1 µg kg⁻¹. The method was validated using blank pork muscle fortified with all four metabolites at 0.5, 1.0 and 2.0 µg kg⁻¹. Recoveries were > 92.3% with RSDs < 8.5% for all four metabolites. The results obtained with HPLC-FLD and LC-MS/MS methods showed very good agreement for pork muscle samples.

N-substituted benzyl matrinic acid derivatives inhibit hepatitis C virus (HCV) replication through down-regulating host heat-stress cognate 70 (Hsc70) expression.

Heat-stress cognate 70 (Hsc70) is a host factor that helps hepatitis C virus (HCV) to complete its life cycle in infected hepatocytes. Using Hsc70 as a target for HCV inhibition, a series of novel N-substituted benzyl matrinic/sophoridinic acid derivatives was synthesized and evaluated for their anti-HCV activity in vitro. Among these analogues, compound 7c possessing N-p-methylbenzyl afforded an appealing ability to inhibit HCV replication with SI value over 53. Furthermore, it showed a good oral pharmacokinetic profile with area-under-curve (AUC) of 13.4 µM·h, and a considerably good safety in oral administration in mice (LD50>1000 mg/kg). As 7c suppresses HCV replication via an action mode distinctly different from that of the marketed anti-HCV drugs, it has been selected as a new mechanism anti-HCV candidate for further investigation, with an advantage of no or decreased chance to induce drug-resistant mutations.

N-(2,4-Dinitro-phen-yl)-1,3-dimeth-oxy-isoindolin-2-amine.

In the title compound, C(16)H(16)N(4)O(6), the planes of the isoindole and dinitro-benzene groups make a dihedral angle between of 84.15 (8)°. The N atom of the isoindole group is displaced by 0.2937 (3) Šfrom the plane through the remaining atoms. An intra-molecular N-H⋯O inter-action occurs. In the crystal, inversion dimers linked by pairs of N-H⋯O hydrogen bonds occur.

Synthesis and in vitro antitubercular evaluation of novel sansanmycin derivatives.

Tuberculosis (TB) is a major health problem worldwide. A series of novel sansanmycin derivatives were designed, semi-synthesized and evaluated for their activity against drug-susceptible Mycobacterium tuberculosis strain H(37)Rv with sansanmycin A (SSA) as the lead. Among these analogs tested, compound 1d possessing an isopropyl group at the amino terminal afforded an increased antimycobacterial activity with a MIC value of 8 µg/mL in comparison with SSA. Importantly, it was active for rifampicin- and isoniazid-resistant M. tuberculosis strain isolated from patients in China. These promising results offer an opportunity for further exploration of this novel class of analogs as antitubercular agents.

(E)-3-[(2-Hy-droxy-naphthalen-1-yl)methyl-idene-amino]-5-(morpholin-4-yl-meth-yl)-1,3-oxazolidin-2-one.

The title compound, C(19)H(21)N(3)O(4), crystallizes with two independent mol-ecules in the asymmetric unit. In both mol-ecules, there is an intra-molecular O-H⋯N hydrogen bond, which correlates with the fact that each mol-ecule adopts an E configuration with respect to the C=N bond. In the crystal, there are C-H⋯O and C-H⋯π inter-actions present.

Synthesis, structure-activity relationship and biological evaluation of anticancer activity for novel N-substituted sophoridinic acid derivatives.

Sophoridine (1), a natural anticancer drug, has been used in China for decades. A series of novel N-substituted sophoridinic acid derivatives were synthesized and evaluated for their cytotoxicity with 1 as the lead. The structure-activity relationship indicated that introduction of an aliphatic acyl on the nitrogen atom might significantly enhance the anticancer activity. Among the compounds, 6b bearing bromoacetyl side-chain afforded a potential effect against four human tumor cell lines (liver, colon, breast, and lung). The mechanism of action of 6b is to inhibit the activity of DNA topoisomerase I, followed by the S-phase arrest and then cause apoptotic cell death, similar to that of its parent 1. We consider 6b promising for further anticancer investigation.

Synthesis, structure-activity relationship and biological evaluation of novel N-substituted matrinic acid derivatives as host heat-stress cognate 70 (Hsc70) down-regulators.

Oxymatrine (1) is a natural anti-hepatitis B virus (HBV) drug that down-regulates host heat-stress cognate 70 (Hsc70) expression through a mechanism different from that of nucleosides. Taking Hsc70 as a target against HBV, 26 novel N-substituted matrinic acid analogs were designed, synthesized and evaluated for their regulation of Hsc70 mRNA expression with 1 as the lead. The SAR analysis revealed that (i) the carboxyl group at the 11-position was required for activity; (ii) introducing of a substituent on the nitrogen atom at the 12-position of 3, especially substituted benzyl, might significantly improve the activity. Among these analogs, compound 9p possessing N-p-methoxylbenzyl afforded an increased anti-HBV effect in comparison with 1. We consider 9p a promising anti-HBV candidate.

Design and synthesis of oxymatrine analogues overcoming drug resistance in hepatitis B virus through targeting host heat stress cognate 70.

Heat-stress cognate 70 (Hsc70) is a host protein required for hepatitis B virus (HBV) replication, and oxymatrine (1) suppresses Hsc70 expression. Taking Hsc70 as a target against HBV, 22 analogues of 1 defined with substituents at position 1, 13, or 14 were synthesized and evaluated for their activity on Hsc70 mRNA expression. The SAR revealed that (i) the oxygen atom at the 1-position was not essential, (ii) increasing electron density on the ring D reduced the activity, and (iii) introducing a proper substituent at the 13- and/or 14-position(s), especially electron-withdrawing groups, might enhance the activity. Among the analogues, 6b possessing 13-ethoxyl afforded an increased activity in respect to 1. Importantly, it was active for either wild-type or lamivudine-resistant HBV, as its target is host Hsc70 but not viral enzymes. LD(50) of 6b in mice was over 750 mg/kg in oral route. We consider compound 6b promising for further investigation.

Small molecular compounds that inhibit hepatitis C virus replication through destabilizing heat shock cognate 70 messenger RNA.

UNLABELLED: Host heat shock cognate 70 (Hsc70) protein is packaged into hepatitis C viral (HCV) particles as a structural component of the virus in the assembly process. It helps HCV RNA release into the cytoplasm in the next infection cycle. The goal of this study is to investigate whether chemically down-regulating host Hsc70 expression could be a novel strategy to interrupt HCV replication. Compounds were screened with an Hsc70 messenger RNA (mRNA) assay. IMB-DM122 was found to be an effective and safe inhibitor for Hsc70 mRNA/protein expression in human hepatocytes. IMB-DM122 inhibited HCV replication through destabilization of Hsc70 mRNA, and the half-life of host Hsc70 mRNA was reduced by 78% after the compound treatment. The Hsc70 mRNA 3' untranslated region sequence is the element responsible for the effect of IMB-DM122 on Hsc70 mRNA. The compound appears to be highly efficient in inhibiting Hsc70-related HCV replication. Treatment of the HCV-infected hepatocytes with IMB-DM122 reduced the virion encapsidation of Hsc70, and therefore disrupted HCV replication and the infection cycle. IMB-DM122 showed considerable good safety in vitro as well as in vivo with no indication of harmful effect on liver and kidney functions. CONCLUSION: Hsc70 might be a new drug target and mechanism to inhibit HCV proliferation.

(E)-1-[(2-Hy-droxy-1-naphth-yl)methyl-idene-amino]-imidazolidine-2,4-dione.

The title compound, C(14)H(11)N(3)O(3), adopts an E or trans configuration with respect to the C=N bond. In the mol-ecule there is an intra-molecular O-H⋯N hydrogen bond involving the hy-droxy substituent at the 2-positon of the naphthalene ring and the adjacent methyl-ene-amino N atom. The mol-ecule is roughly planar, the dihedral angle between the naphthalene and imidazolidine-2,4-dione mean planes being 8.4 (1)°. In the crystal, pairs of N-H⋯O hydrogen bonds link mol-ecules into inversion dimers. These dimers are futher linked via C-H⋯O inter-actions, forming a three-dimensional network.

Methyl 3-[(E)-(2-hy-droxy-1-naphth-yl)methyl-idene]carbazate.

The title compound, C(13)H(12)N(2)O(3), has an E configuration with respect to the C=N bond: the conformation is stabilized by an intramolecular O-H⋯N hydrogen bond. In the crystal, an N-H⋯O interaction links the molecules into a C(4) chain along [100].

Synthesis and activity evaluation of phenylurea derivatives as potent antitumor agents.

We have discovered several tubulin-active compounds in our previous studies. In the establishment of a compound library of small molecule weight tubulin ligands, 14 new N-3-haloacylaminophenyl-N'-(alkyl/aryl) urea analogs were designed and synthesized. The structure-activity relationship (SAR) analysis revealed that (i) the order of anticancer potency for the 3-haloacylamino chain was following -CH(2)Br>-CHBrCH(3); (ii) the N'-substituent moiety was not essential for the anticancer activity, and a proper alkyl substitution might enhance the anticancer activity. Among these analogs, the compounds 16j bearing bromoacetyl at the N'-end exhibited a potent activity against eight human tumor cell lines, including CEM (leukemia), Daudi (lymphoma), MCF-7 (breast cancer), Bel-7402 (hepatoma), DU-145 (prostate cancer), DND-1A (melanoma), LOVO (colon cancer) and MIA Paca (pancreatic cancer), with the IC(50) values between 0.38 and 4.07 microM. Interestingly, compound 16j killed cancer cells with a mechanism independent of the tubulin-based mechanism, indicating a significant change of the action mode after the structure modification.

Berberine analogues as a novel class of the low-density-lipoprotein receptor up-regulators: synthesis, structure-activity relationships, and cholesterol-lowering efficacy.

Twenty-nine derivatives of berberine (1) or pseudoberberine (2) were designed, semisynthesized, and evaluated for their up-regulatory activity on the low-density-lipoprotein receptor (LDLR) expression. SAR analysis revealed that (i) the methylenedioxy group at the 2- and 3-position is an essential element to keep the activity, (ii) the 7-position quaternary ammonium and planar structure of the compound are activity-required, and (iii) addition of electron-donating groups at the 7- or 13-position reduced the activity. Of the compound 1 analogues, compound 2 exhibited an increased activity on LDLR expression compared to 1. In the hyperlipidemic rats, compound 2 (100 (mg/kg)/day) reduced blood CHO and LDL-c by 42.6% and 49.4%, respectively, more efficient than 1 did (p < 0.01 for both). The results were confirmed in the hyperlipidemic mice. LD(50) of 2 in mice was over 5000 mg/kg (oral). We consider compound 2 a promising cholesterol-lowering drug candidate.

Synthesis and activity evaluation of benzoylurea derivatives as potential antiproliferative agents.

3-Haloacylamino benzoylureas (3-HBUs) consist of a new family of tubulin ligands that kill cancer cells through mitotic arrest. In exploring the structure-activity relationship (SAR), 17 analogues defined through variations of formylurea at the 1-position of the aromatic ring were synthesized. SAR analysis revealed that (i) the p-pi conjugation between the aromatic ring and formylurea was essential; (ii) suitable aryl substitutions at the N'-end increased anticancer activity with a mechanism different from that of parent compounds; and (iii) introduction of pyridyl at the N'-end provided an opportunity of making soluble salts to improve bioavailability. Among the analogues, 16c bearing 3,4,5-trimethoxyphenyl and 16g bearing 2-pyridyl at the N'-end showed an enhanced activity and were active in hepatoma cells that were resistant to tubulin ligands including the parent compounds. Furthermore, 16c and 16g killed cancer cells with a mechanism independent of mitotic arrest, indicating a change of action mode.

(E)-2-Hydroxy-naphthalene-1-carb-al-de-hyde semicarbazone.

The title compound, C(12)H(11)N(3)O(2), adopts an E or trans configuration with respect to the C=N bond. There is an intra-molecular O-H⋯N hydrogen bond involving the hydroxyl H atom and an N atom of the hydrazine group. In the crystal structure, mol-ecules are connected via N-H⋯O hydrogen bonds, forming a three-dimensional network.

Benzoylurea derivatives as a novel class of antimitotic agents: synthesis, anticancer activity, and structure-activity relationships.

Forty-six new compounds were synthesized on the basis of our knowledge of the 3-haloacylamino benzoylurea (HBU) series. Structure-activity relationship (SAR) analysis indicates that (i) the configuration of the chiral center in 1 (JIMB01) is not indispensable for the activity, (ii) the phenyl ring is essential, and (iii) a substitution at the 6-position of the phenyl ring with a halogen enhances the activity. Among the analogues, 11e and 14b bearing 6-fluoro substitution showed potent activities against nine human tumor cell lines, including CEM (leukemia), Daudi (lymphoma), MCF-7 (breast cancer), Bel-7402 (hepatoma), DU-145 (prostate cancer), PC-3 (prostate cancer), DND-1A(melanoma), LOVO (colon cancer), and MIA Paca (pancreatic cancer) with IC 50 values between 0.01 and 0.30 microM. 14b inhibited human hepatocarcinoma by 86% in volume in nude mice. The mechanism of 14b is to inhibit microtubule assembly, followed by the M-phase arrest, bcl-2 inactivation, and then apoptosis. We consider 14b promising for further anticancer investigation.