Synthesis and Evaluation of L-Glutamic acid Analogs as Potential Anticancer Agents

Four N-(benzenesulfonyl)-L-glutamic acid bis(p-substituted phenylhydrazides) were synthesized and evaluated for anticancer activity in vitro in DU-145 and PC-3 prostate cancer and in COLO-205 colon cancer cell lines by MTT assay. The analog with the nitro group substitution exhibited potent activity (% Inhibition 84.7 and 72.0 in DU-145 and PC-3 respectively at 80 μg/ml concentration). Another series of substituted 1-(benzenesulfonyl)-5-oxopyrrolidine 2-carboxamides (11a-f) were synthesized and evaluated for anticancer activity in vitro in colon (COLO-205), breast (Zr-75-1) and prostate (PC-3) cancer cell lines by MTT assay using adriamycin as standard. Test compounds 11a-c showed potent activity (% Inhibition 61.2 to 79.2 at 20 μg/ml and 67.2 to 87.2 at 40 μg/ml) in PC-3 cell line which is superior to the activity of Adriamycin. In comparison compounds 11d-f were less potent. In Zr-75-1 cell line 11a-e showed % inhibition ranging from 32.4 to 54.9 at 10 μg/ml concentration while in COLO-205 cell line 11a-f showed poor activity.     

Synthesis and Pharmacological Evaluation of Analogs of Indole-Based Cannabimimetic Agents

Aminoalkylindoles (AAIs), although structurally dissimilar from the classical cannabinoids, are known to be capable of binding to cannabinoid receptors and of evoking cannabinomimetic responses. With the aim of investigating the structure–activity relationships (SAR) for the binding of non-classical agonists to CB1 and CB2 cannabinoid receptors, we designed and synthesized a series of indole derivatives. The compounds were tested for their analgesic action by formalin test and compared to WIN 55212-2, an AAI acting to the cannabinoid receptors. In receptor binding assay, compound 5 showed affinity for the CB1 receptor comparable to WIN 55212-2.     

Novel Pirfenidone Analogs as Antifibrotic Agents: Synthesis and Antifibrotic Evaluation of 2-Pyridones and Fused Pyridones

A new series of substituted 1-(2-ethylphenyl)-2-oxo-1,2-dihydropyridine-3-carbonitriles have been synthesized. Moreover, substituted bicyclic derivatives e.g. thieno[3,4-c]pyridone, pyrido[3,4-c]pyridone, benzo[c]pyridone, and tricyclic derivatives, chromeno[3,4-c]pyridones have been prepared and evaluated for their antifibrotic activity. Among the tested compounds, compounds 4d and 5a exhibited potent antifibrotic activity without harmful side effects on liver and kidney functions. Detailed synthesis, spectroscopic and biological data are reported.     

紫外分光光度法快速测定肌苷注射液中肌苷的含量

目的 本文建立一种肌苷注射液的紫外分光光度法含量测定。方法 以水为溶媒，检测波长在248nm的条件下，对肌苷注射液进行定量分析。结果 肌苷在浓度3μg-18μg范围内线性良好，以吸收系数法得其平均回收率为100.1%,RSD为0.9%。结论 结果表明该方法稳定可靠、简便、快速、重现性好。     

Indolyl Compounds as Antiinflammatory Agents

Eight new ω-(indol-3-yl)alkane carboxamides were synthesized and studied for their antiinflammatory activities against carrageenin induced paw oedema in albino rats. Six compounds exhibited various degrees of antiinflammatory activity, two compounds showed no activity. The most potent compound of the present series, 1-(indol-3-yl)-N-{4-[1-(4-methylphenyl)piperazinyl]phenyl}acetamide (7) as well as phenylbutazone showed dose dependent inhibition of rat paw oedema. The ulcerogenic activities of compound 7 and phenylbutazone were also dose dependent. However, 7 showed a much lower ulcerogenic activity. In view of its potent antiinflammatory activity, minimal ulcerogenic liability and low acute toxicity compound 7 appears promising.     

Drugs as Agents of Control

Abstract

In-depth interviews and a qualitative methodology are used to examine the drug careers of a nonrandom sample of 31 current or former marijuana smokers. Three user typologies were developed to describe the complex development of marijuana careers over time: Druggies, Weekend Warriors, and Grown-ups. Druggies and Weekend Warriors tend to use marijuana (and alcohol) fairly heavily during the early phases of their careers; Druggies pass this stage quickly and eventually move on to harder drugs and periods of chronic substance abuse. Gradual assumption of adult identities and roles allow Weekend Warriors to moderate their marijuana (and other drug use), which steadily declines throughout the remainder of their careers. Grown-ups tend to use marijuana and all drugs moderately during the beginning phases of their careers, eschew experimentation with harder drugs, and generally progress to very controlled use of marijuana and other intoxicants (or abstinence) in the later stages of their careers. The social process of using marijuana teaches the majority of users to quit or how to integrate its use into a lifestyle that can reasonably be described as normal or conventional. Lastly, two future directions for drug career research are suggested.     

Polyacetylenes Function as Anti-Angiogenic Agents

PURPOSE: To investigate the antiangiogenic effects of plant extracts and polyacetylenes isolated from Bidens pilosa Linn., which is a popular nutraceutical herbal tea and folk medicine in anti-inflammatory, antitumor, and other medications worldwide. METHODS: Anti-cell proliferation, anti-tube formation, and cell migration assays were used for the valuation of bioactivities of target plant extracts and phytocompounds against angiogenesis. Bioactivity-guided fractionation, HPLC, and various spectral analyses were used to identify active fraction and phytocompounds for anti-angiogenesis. RESULTS: We show that an ethyl acetate (EA) fraction of B. pilosa exhibited significant anti-cell proliferation and anti-tube formation activities against human umbilical vein endothelium cells (HUVEC). Bioassay-guided fractionation led to isolation of one new and one known polyacetylenes, 1,2-dihydroxytrideca-5,7,9,11-tetrayne (1) and 1,3-dihydroxy-6(E)- tetradecene-8,10,12-triyne (2), respectively, from the EA fraction. Compounds 1 and 2 manifested highly specific and significant activities against HUVEC proliferation with IC50 values of 2.5 and 0.375 microg/ml, respectively, however, compound 1 had a more potent effect on preventing tube formation of HUVEC than compound 2 at a dose of 2.5 microg/ml. Western blot analysis showed that both compounds upregulated p27(Kip) or p21(Cip1), cyclin-dependent kinase inhibitors, in HUVEC. CONCLUSIONS: This is the first report to demonstrate that polyacetylenes possess significant anti-angiogenic activities and the ability to regulate the expression of cell cycle mediators, for example, p27(Kip1), p21(Cip1), or cyclin E.     

高效液相色谱法测定肌苷葡萄糖注射液中肌苷的含量

目的：建立肌苷葡萄糖注射液中肌苷含量的高效液相色谱测定法。方法：采用Hypersil ODS柱，以甲醇 水(10∶90)为流动相，检测波长为248 nm，流速1.0 mL·min 1。结果：肌苷浓度在8～40 μg·mL 1范围内有良好线性关系(r＝0.999 9)。平均回收率102.3%(n＝5)，RSD为0.7%。结论：该法简便、快速、准确，可测定注射液中肌苷的含量。     

Novel Benzimidazole Analogs as Inhibitors of EGFR Tyrosine Kinase

A series of new benzimidazole congeners were synthesized, and their structures were elucidated on the basis of elemental analyses and spectral studies ((1) H NMR, FT-IR and EI-MS). Preliminary pharmacokinetic studies showed a promising outlook for further in vivo evaluation. The newly synthesized compounds were tested in vitro on human breast carcinoma cell line (MCF-7) in which EGFR is highly expressed. Most of the tested compounds exhibited antitumor activity with IC(50) values in the micro to nano molar range.     

复方肌苷口服液中肌苷含量的两种测定方法比较

目的 比较复方肌苷口服液中肌苷含量的两种测定方法.方法 采用紫外分光光度(UV)法和高效液相色谱(HPLC)法测定复方肌苷口服液中肌苷含量.结果 紫外分光光度法回收率为99.4%,RSD=0.59%;高效液相色谱法回收率为100.2%,RSD=1.11%.结论 两种方法测定结果一致.     

New Quinolines as Potential CNS Agents

The compounds 1a—1l and 2a—2m were synthesized by condensation of various aryl-1-(4-aminophenyl)piperazines and substituted piperidines with substituted 4-chloroquinolines. The compounds were screened for their monoamine oxidase (MAO) inhibitory activities (in vitro) and various CNS activities (in vivo). Some compounds showed promising MAO inhibitory and antidepressant activities. The compounds did not produce acute neurological deficits and have low toxicity. Compound 1b is the most active member of the series. Structure-activity relationships are discussed.     

MraY Inhibitors as Novel Antibacterial Agents

MraY presents all necessary biological requirements to be considered as a target of interest for the discovery of novel antibacterials. Furthermore, several inhibitors aimed at this enzyme have been discovered. Amphomycin, which is currently used as a topical antibacterial in the veterinary industry is one of them, but the major source of future developments resides in the nucleoside based inhibitors group. This group has been subdivided into classes: Tunicamycins, Ribosamino-uridines, Uridylpeptides and Capuramycins. Analysis of pharmacological behaviours observed with several compounds within these classes, shows that broad-spectrum antibacterial activity, including relevant resistant strains and in vivo efficacy without toxicity are achievable. Among them, Caprazamycins, Muraymycins, Riburamycins and Capuramycins present the most promising profiles.