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Tuberculosis (TB) is one of the deadliest infectious diseases worldwide. The drug discovery process of novel, safe and effective agents to combat TB involves identification of new molecular targets and novel chemical scaffolds. The current anti-TB drug pipeline includes several small molecules with more to follow as new candidates are disclosed. This review highlights the most significant findings described in 78 international, European and US patents for chemically diverse compounds as prospective anti-TB medications. Main points of emphasis include chemical classification, in vitroand in vivoactivity, ADME/Tox profile and mycobacterial target as described in each patent. The collective mass of compounds disclosed in the reviewed patents introduces new candidates as potential therapeutic agents for TB infections.

Depression is a major health problem currently recognized as a leading cause of morbidity worldwide. In the United States alone, depression affects approximately 20% of the population. With current medications suffering from major shortcomings that include slow onset of action, poor efficacy, and unwanted side effects, the search for new and improved antidepressants is ever increasing. In an effort to evade side effects, people have been resorting to popular traditional herbal medicines to relieve the symptoms of depression, and there is a need for more empirical knowledge about their use and effectiveness. This review provides an overview of the current knowledge state regarding a variety of natural plant products commonly used in depression. Herbal medicines discussed that have been used in clinical trials for the treatment of mild to moderate depression states include the popular St. John’s wort, saffron, Rhodiola, lavender, Echium, and the Chinese formula banxia houpu. In addition, new emerging herbal products that have been studied in different animal models are discussed including Polygala tenuifolia, the traditional Chinese herbal SYJN formula, gan mai da zao, and Cannabis sativa constituents. A comprehensive review of the chemical, pharmacological, and clinical aspects of each of the reviewed products is provided. Finally, recent preclinical studies reporting the antidepressant action of marine-derived natural products are discussed at the end of the review.

Ethyl 8-oxo-5,6,7,8-tetrahydrothiazolo[3,2-a][1,3]diazepin-3-carboxylate (HIE-124) is one of a new generation of ultra-short-acting hypnotics. A high-performance thin-layer chromatographic (HPTLC) method has been established as the first reported method for quantitative analysis of HIE-124 in plasma. Baseline resolution between HIE-124 and diazepam (internal standard) was achieved on HPTLC plates with chloroform—ethyl acetate 80:20 (v/v) as mobile phase. Densitometric detection was performed at 265 nm. The method was linear in the range 40–400 μg mL−1(R= 0.997) and recoveries of the drug were in the range 93–102% at 80–350 μg mL−1. Within-run and between-run precision calculated as RSD [%], and accuracy calculated as percentage error were in the ranges 2.1–4.6% and 0.8–6.9%, respectively. The limits of detection (LOD) and quantification (LOQ) in spiked human plasma were 20 and 40 μg mL−1(40 and 80 ng per band), respectively.

A high-performance thin-layer chromatographic (HPTLC) method has been established for determination of sildenafil citrate in commercial products. The compounds were separated on silica gel, with CHCl3-MeOH-diethylamine, 90 + 10 + 1 (v/v), as mobile phase, and the analyte spots were quantified densitometrically at λ = 305 nm. Recovery of sildenafil citrate was 100.6 and 98.2%, for pure and spiked samples, respectively. Method precision and specificity were also validated. The method was used for determination of sildenafil in four pharmaceutical products and three aphrodisiac herbal preparations which were claimed to be totally natural. Levels of sildenafil in the pharmaceutical products ranged from 49.7 to 50.5 mg per tablet. Sildenafil was also detected in one herbal preparation at a concentration of 85.0 mg per capsule.

A high-performance thin-layer chromatographic method for determination of parthenolide has been validated for recovery, accuracy, specificity, and precision and applied to four feverfew products. Chromatography was performed on silica gel plates with ethyl acetate-n-hexane, 3 + 2 (v/v) as mobile phase. Parthenolide was visualized by dipping plates into p-anisaldehyde reagent and heating at 105°C for 5 min. Densitometric quantification of analyte spots was achieved by scanning the plates at λ = 543 nm after derivatization. The method is precise with CV[%] < 5.00; calibration recovery = 101.12 ± 4.11% and overall accuracy = 101.14 ± 4.47%. The levels of parthenolide in the products analyzed ranged from 0.03 to 0.24%.

Goldenseal (Hydrastis canadensis L., Ranunculaceae) is an ingredient of various dietary supplements intended for enhancing general body immunity. Many goldenseal products are currently available in the United States, either alone or in combination with echinacea. In most products, the content of the main active alkaloids of goldenseal, hydrastine and berberine, is not indicated on the label. A high-performance liquid chromatography (HPLC) method has been developed for the detection and quantification of hydrastine and berberine in a number of products obtained from the United States market. The method uses a Phenomenex^® Luna C18 column, a mobile phase consisting of solvent A (100 mM sodium acetate/acetic acid, pH 4.0) and solvent B (acetonitrile/methanol; 90/10, v/v). Elution was run at a flow rate of 1.0 mL/min, with a linear gradient of 80– 40% A in B over 20 min and ultraviolet detection at 290 nm. A wide range of content variation was observed for both alkaloids in the tested samples. © 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:817–822, 2001

Phytochemical investigation of the leaves of Paullinia pinnata L. (Sapindaceae) resulted in the isolation of the two new flavone glycosides characterized as diosmetin-7-O-(2‘ ‘-O-β-d-apiofuranosyl-6‘ ‘-acetyl-β-d-glucopyranoside) (1) and tricetin-4‘-O-methyl-7-O-(2‘ ‘-O-β-d-apiofuranosyl-6‘ ‘-acetyl-β-d-glucopyranoside) (2).

Maesanin (1) is a naturally occurring bioactive benzoquinone isolated from the fruits of Maesa lanceolata (Myrsinaceae). Three carboxylic acid metabolites of maesanin were isolated in the course of a prospective microbial transformation study. The first metabolite, 2, was produced by Lipomyces lipofer ATCC 10742 and was characterized as (Z)-15-(2‘-hydroxy-5‘-methoxy-3‘,6‘-dioxocyclohexa-1‘,4‘-dienyl)pentadec-5-enoic acid. Metabolites 3 and 4 were produced by Rhodotorula rubra ATCC 20129 and were characterized as 6-(2‘-hydroxy-5‘-methoxy-3‘,6‘-dioxocyclohexa-1‘,4‘-dienyl)hexanoic acid and 4-(2‘-hydroxy-5‘-methoxy-3‘,6‘-dioxocyclohexa-1‘,4‘-dienyl)butanoic acid, respectively.

Microbial transformation of the semisynthetic sesquiterpene artemether, using Cunninghamella elegans and Streptomyces lavendulae, resulted in the isolation of five microbial metabolites that were characterized on the basis of their ¹H and ¹³C NMR spectral data. These metabolites were identified as 9β-hydroxyartemether, 9α-hydroxyartemether, ring-rearranged 9β-hydroxyartemether, 3α-hydroxydeoxyartemether, and 14-hydroxyartemether. The latter three compounds are new and are being reported here for the first time.

Many studies on the biological activities of nutmeg continue to appear in the literature. The most common targets include GIT, CNS, oxidative stress and inflammation. However, results obtained from most studies are often inconsistent due to the variability of utilized samples, lack of standardized nutmeg products or insufficient amounts of pure compounds for comprehensive follow-up investigation. To address the consistency and supply issue we utilized available technology to develop a reproducible procedure for preparation of specific extracts and isolation of the major phenolic constituents present in nutmeg kernel. A well-defined and reproducible sequence of extraction, fractionation and chromatographic purification was adopted and was guided by HPLC fingerprinting. Spectroscopic methods, mainly NMR, and mass spectrometry were utilized to identify each compound. Thirteen compounds were isolated in a pure form and identified as: elemicin (1), isoelemicin (2), myristicin (4), surinamensin (5), malabaricone C (6), 2-(3′-allyl-2′,6′-dimethoxy-phenyloxy)-1-acetoxy-(3,4-dimethoxyphenyl)-propyl ester (7), methoxylicarin A (8), licarin A (9), malabaricone B (10), licarin C (11), 5′-methoxylicarin B (12), licarin B (13), and 2-(3′-allyl-2′,6′-dimethoxy-phenyloxy)-1-methyl-5-methoxy-1,2-dihydrobenzofuran (3, a new compound). With repeated isolation runs, these pure compounds can be prepared in quantities sufficient for biological evaluation as needed. The availability of purified compounds will also allow the development of specific, accurate, and sensitive analytical procedures for pharmacokinetic studies and for quality control of nutmeg products. Both aspects are essential for nutmeg-focused drug discovery. The same approach can also be adapted to other medicinal plants of potential interest.

The roots of Ferula hermonis Boiss yielded two new daucane esters, 14-(4‘-hydroxybenzoyloxy)dauc-4,8-diene (1) and 14-(4‘-hydroxy-3‘-methoxybenzoyloxy)dauc-4,8-diene (2), together with the four known sesquiterpenes jaeschkeanadiol p-hydroxybenzoate (3), jaeschkeanadiol benzoate (4), jaeschkeanadiol (5), and epoxyjaeschkeanadiol (6). The identities of the isolated compounds were ascertained primarily using NMR and MS data. Compounds 1 and 3 exhibited antimicrobial activity against Staphylococcus aureus with IC50 1.5 and 3.5 μg/mL, respectively, and against Methicillin-resistant S. aureus with IC50 2.0 and 4.0 μg/mL, respectively.

In our ongoing search for anti-inflammatory and neuroprotective agents of natural origin, the total methanolic extract (MPE) of horse apple (Maclura pomifera)and its two major prenylated isoflavones, osajin (OSA) and pomiferin (POM), were evaluated in vitrofor their ability to affect four mediators of inflammation and to inhibit tau protein fibrillization. The two isoflavones were effective in enhancing the activity of NSAID activated gene (NAG-1) at 2.5 μg/mL (1.5 – 1.8 fold increase) and inhibiting iNOS and NF-κB activity with IC50values in the range of 6 – 13 μg/mL. Pomiferin also inhibited intracellular oxidative stress with IC50of 3.3 μg/mL, while osajin did not show any effect. The extract activated NAG-1 and inhibited iNOS and oxidative stress without affecting NF-κB. As observed by transmission electron microscopy (TEM), MPE, OSA and POM also inhibited arachidonic acid-induced tau fibrillization in a concentration-dependent manner.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.