Synthesis, binding, and functional properties of tetrahydroisoquinolino-2-alkyl phenones as selective σR/TMEM97 ligands.

Sigma-2 receptor (σR/TMEM97) has been implicated to play important roles in multiple cellular dysfunctions, such as cell neoplastic proliferation, neuro-inflammation, neurodegeneration, etc. Selective σ ligands are believed to be promising pharmacological tools to regulate or diagnose various disorders. As an ongoing effort of discovery of new and selective σ ligands, we have synthesized a series of tetrahydroisoquinolino-2-alkyl phenone analogs and identified that 10 of them have moderate to potent affinity and selectivity for σR/TMEM97.

Sigma ligands as potent inhibitors of Aβ and AβOs in neurons and promising therapeutic agents of Alzheimer's disease.

Alzheimer's disease (AD) is an age-related neurodegenerative disease and characterized by dementia, memory decline, loss of learning and cognitive disorder. The main pathological features of AD are the deposition of amyloid plaques and the formation of neurofibrillary tangles (NFTs) in the brain. The current anti-AD drugs have shown unsatisfactory therapeutic results.

Sigma-2 Receptor as a Potential Drug Target.

Sigma-2 receptor plays key roles in promoting tumor cell apoptosis, enhancing efficacy of anti-tumor drugs, blocking signal transduction controlled by Aβ oligomers, regulating Ca homeostasis and protecting nerve cells. Studies indicated that sigma-2 receptor may be closely coupled with ROS, LDL, mTOR, RAS, PLC/PKC, lysosomal autophagy and mitochondrial super oxidative stress. In addition, the high expression of this receptor in proliferating cells and nerve cells indicates that sigma-2 receptor is an ideal molecular target for imaging and therapeutic development for cancer, Alzheimer's disease, schizophrenia and traumatic brain injury.

Synthesis and evaluation of pyrimidoindole analogs in umbilical cord blood ex vivo expansion.

The scarcity of hematopoietic stem cells (HSCs) significantly hindered their clinical potentials. Umbilical cord blood (UCB) has become the leading source of HSCs for both research and clinical applications. But the low content of HSCs in a single UCB unit limited its use only to pediatric patients.

Isolation, synthesis, and cytotoxicity evaluation of two impurities in nomegestrol acetate.

Nomegestrol acetate (NOMAc) is a synthetic progesterone analog and classified as a fourth-generation progestin. It has been approved in many countries for oral contraception, hormonal replacement therapy (HRT), and treatment of various gynecological disorders. There are several synthetic routes reported for the synthesis of NOMAc and they all share the very similar last three to five steps toward the conversion of 6-methylene to 6-methyl-6,7-unsaturated structure.

Synthesis and pharmacological evaluation of 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives as sigma-2 receptor ligands.

Increasing evidences have implicated that sigma-2 receptor is a biomarker and significantly over-expressed in many proliferative cancer cells with no or low expression in normal cells. Sigma-2 receptor selective ligands have been successfully used as valuable tools to study its pharmacological functions, tumor imaging, and cancer therapeutics or adjuvants. 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinolinylalkyl benzamides are among a few categories of structures that have demonstrated high affinities and selectivities for sigma-2 receptor and been used extensively as study tools in various tumor imaging and therapy.

Synthesis and evaluation of tetrahydroindazole derivatives as sigma-2 receptor ligands.

A series of tetrahydroindazole derivatives were synthesized and evaluated for their affinities for both sigma-1 and sigma-2 receptors. These compounds are hybrid structures of a tetrahydroindazole substituted benzamide and a 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline moiety or a 9-azabicyclo[3.3.

Sigma-2 receptor ligands and their perspectives in cancer diagnosis and therapy.

The sigma-2 receptor is highly expressed in various rapidly proliferating cancer cells and regarded as a cancer cell biomarker. Selective sigma-2 ligands have been shown to specifically label the tumor sites, induce cancer cells to undergo apoptosis, and inhibit tumor growth. Sigma-2 ligands are potentially useful as cancer diagnostics, anticancer therapeutics, or adjuvant anticancer treatment agents.

catena-Poly[[[aqua-(1,10-phenanthro-line)manganese(II)]-μ-adamantane-1,3-dicarboxyl-ato] monohydrate].

In the title coordination polymer, {[Mn(C(12)H(14)O(4))(C(12)H(8)N(2))(H(2)O)]·H(2)O}(n), the Mn(II) atom has a highly distorted cis-MnN(2)O(4) octa-hedral geometry arising from its coordination by a bidentate phenanthroline ligand, a water mol-ecule and monodentate and bidentate adamantane-1,3-dicarboxyl-ate dianions. The bridging dianion leads to [001] chains in the crystal. The chains are linked by O-H⋯O hydrogen bonds, involving both the coordinated and uncoordinated water mol-ecules, thereby forming a two-dimensional network.

[Observation on therapeutic effect of electroacupuncture for treatment of sudden hearing loss].

Objective: To observe the therapeutic effect of electroacupuncture for treatment of sudden hearing loss and to compare with western medicine therapy.

Methods: Sixty cases were randomly divided into an electroacupuncture group and a medication group, 30 cases in each group. The electroacupuncture group was treated with electroacupuncture at Tinghui (GB 2), Yifeng (TE 17), Hegu (LI 4), Xiaxi (GB 43), Zhongzhu (TE 3), etc.

[Effects of Feiji Formula on lung cancer metastasis in mice].

Objective: To observe the effects of Feiji Formula, a compound traditional Chinese herbal medicine, on lung cancer metastasis in mice.

Methods: The lung cancer metastasis model of mice was established in this experiment study. Twenty-four mice were randomly divided into three groups: untreated group, cisplatin group and Feiji Formula group.

[Intervention effect of Feiji Recipe on immune escape of lung cancer].

Objective: To evaluate the intervention effect of Feiji Recipe (FJR) on tumor immune escape.

Methods: In the prospective randomized control study, 60 cases of middle stage and advanced non-small cell lung cancer (NSCLC) with qi-yin deficiency syndrome were randomly assigned to the treatment group and the control group, 30 in each group. The levels of CD+ CD25+ Tr, interleukin-10 (IL-10), vascular endothelial growth factor (VEGF), sCD44v6 and transforming growth factor-beta1 (TGF-beta1) of peripheral blood were observed before and after treatment, and the clinical efficacy of FJR was evaluated depending upon the changes in tumor size, Karnofsky Performance scoring (KPS) and TCM syndrome.

[Changes of trace elements in regional lymph nodes of gastric carcinoma].

Objective: To explore the relationship between the changes of trace elements and lymphatic metastasis in gastric carcinoma.

Methods: Trace elements including Fe, Mg, Mn, Ca, Cu, Zn, Se were measured in primary gastric carcinoma and regional lymph nodes from 40 patients with gastric carcinoma, and compared among the primary tumor, metastatic, and non-metastatic nodes.

Results: There were no significant differences in the contents of Fe, Mg, Mn and Ca among primary gastric tumors, regional lymph nodes with or without metastasis (P=0.

[Effect of saikosaponins on epileptic rat electroenciphalogram].

Objective: To study the effect of saikosaponins on the electroencephalogram (EEG) of epileptic rats to evaluate its therapeutic effect against epilepsies.

Methods: Sixty 8-week-old healthy SD rats were randomized into normal control group (A), epileptic model group (B), lamotrigine group (C), and 3 saikosaponin groups of small, moderate and high doses (D, E, and F groups, respectively), with 10 rats in each group. Penicillin was used to induce epilepsy in the latter 5 groups, and the EEG and onset of epileptic seizures were observed in each group.