Medicinal Chemistry

A new polyphenol, Potentillanin A (1), together with two known compounds (2–3), was isolated from the chloroform soluble fraction of Potentilla freyniana. The structure of Potentillanin A (1) was elucidated by spectroscopicmethods.

Nowadays, people are gaining interest on natural products due to the health conscious and awareness of the side effect caused by synthetic products. Malaysia is one of the top biodiversity, which host rich diversity of indigenous fruit, which could be a potential source of nutraceutical, antioxidant and pharmaceuticals. Dacryodes rostrata is an indigenous fruit found in Sarawak, Malaysia and is reported to be rich in oil, protein, minerals and could be a potential source of natural antioxidants. Thus, in this work, antioxidant components and antioxidant capacities of the extracts of peel, pulp and seeds of D. rostrata were evaluated. Total phenolic (1008 ± 24 mg/g GAE DW) and flavonoid contents (2551 ± 37 mg/g QE DW) of the seed extracts were higher when compared to peel and the pulp extracts. In addition, 1,1-diphenyl-2-picryl hydrazyl (DPPH) free radical scavenging activity of the seed extracts were higher (63%), compared to peel (25%) and pulp (18%). Ferric reducing antioxidantpower (FRAP) values of the seeds (1.25mM FeSO4 equivalent) exhibited highest activity when, compared with peel (0.29 mM FeSO4 equivalent) and pulp (0.90mM FeSO4 equivalent). Seed extract also showed highest total antioxidant capacity determined by phosphomolybdenum method. Liquid chromatography-mass spectra (LC-MS) of the seed extracts from D. rostrata revealed the presence of phytochemicals in the form of gallic acid, ellagic acid, catechin, epicatechin and apigenin. Thus, D.rostrata seed extracts is having potent antioxidant capacity and could be used as a natural source of antioxidants.

To search for novel nitric oxide (NO)-releasing anti-tumor agents, two series of furoxan-based NO-releasing derivatives of 23-Hydroxybetulinic acid and 3-oxo-23-hydroxybetulinic acid were designed and synthesized. The nitrate/nitrite levels in the cell lysates were assayed and the results showed that these derivatives could produce high levels of NO in vitro. Then the antiproliferative activity of these hybrids against four human cancer cell lines was further determined, among which, compound 20a was the most promising derivative with an IC50 under 10 μM on all tested cell lines. The preliminary structure-activity relationships were concluded based on present experimental data.

Glutathione, a non-protein thiol is most abundant in cells and glutathione-glutathione disulfide is the major redox pair in animal cells. Its synthesis is from two main enzymes gamma glutamyl cysteinyl synthetase and GSH synthetase. Also cysteine availability as N-acetyl cysteine and GSH feedback mechanism determines the reduced glutathione status of the cell. Additionally parenteral NAC, cystine, methionineare effective precursors of cysteine for tissue GSH synthesis. Adequate protein in the diet is crucial for tissue GSH synthesis. The role of NAC as an antioxidant, in gene expression, and regulation of cellular events must be emphasized. GSH deficiency contributes to oxidative stress and it progresses in diseased conditions such as HIV, AIDS, cancer, diabetes, also metabolic syndrome. New knowledge of the nutritional regulation of GSH metabolites is critical to improve health and treat these diseases.

Indian medicinal plants have potent effects in treating diseases such as hypercholesterolemia. This review was performed on published Indian articles on hypocholesterolemic effect of Indian medicinal plants through literature search using Cochrane Library Database, Embase, Sci-finder, Pubmed with MeSH keywords and abstracts of Medicinal and Aromatic plants. All databases were searched from their respective inception until April 2011. About 15,620 papers were obtained using related titles and keywords through the electronic databases as well as various other sources. Therefore, 110 papers were finalized on native and naturalized Indian medicinal plants (24) belonging to various families and were then reviewed. Hypocholesterolemic effect of Indian medicinal plants was furnished with available animal models and clinical trials, which contribute to design new strategies to manage hypercholesterolemia.

The use of antibioticsin health delivery is inevitable since it is one of the most prescribed medications. The quality and efficacy of these medications are crucial in health systems since they can affect the quality of healthcare delivery. The study was designed to determine the quality and activity of some penicillins on the Ghanaian market. A total of 54 samples (29 capsules and 25 suspensions) of different brands and batches were collected from different pharmacies in Accra and Kumasi, Ghana, from October 2011 to May 2012. The activity (zones of inhibition) and minimum inhibitory concentration (MIC) of the samples were determined by the agar-well diffusion and micro-dilution methods respectively against two typed strains of Gram-negative and Gram-positive bacteria. Quality of the samples was determined quantitatively by developed and validated HPLCmethods. The MICs of flucloxacillin and cloxacillin samples were ≥ 1400 μg/mL, whiles that of amoxicillin samples were ≥ 200 μg/mL, with reference to the standard antibiotics which gave MICs of 200 to 800 μg/mL against all the test bacteria with the suspensions exhibiting higher antimicrobial activity. Specificity, linearity, precision and accuracy of the developed HPLC method were determined. HPLC analysis of the samples revealed that 75% of amoxicillin capsule samples and 92.3% of amoxicillin suspension samples contained the right amount of active pharmaceutical ingredient (API) with percentages ranging from 93.2 to 104.3% and 81.0 to 104.1% respectively. For samples of flucloxacillin capsules, 62.5% of the samples showed API content from 96 to 120.5%. All the suspension samples have their API within BP and USP specification of 114.4 to 120.0%. Capsules (58.6%) of all the samples contained the right API whereas 64% of them were recorded for suspensions. Out of the 54 samples evaluated, 61.1% were within the BP and USP specifications. The biological assay revealed higher MIC values for all the penicillin samples evaluated compared with the reference samples. Among the samples evaluated, amoxicillin showed better quality of 82.8% as compared to flucloxacillin (31.3%) and cloxacillin (44.4%) samples. Efforts should therefore be made to improve the quality and storage conditions of these antibiotics and also constant monitoring and surveillance of activity and potency of these antibiotics should be done.

A highly sensitive sandwich-type ECLIA technique using ruthenium complexes as labels was reported. Superparamagnetic nanoparticles were synthesized with a diameter of 12 nm through a coprecipitation method and used as the matrix solid-phase. Then, the ECL targets of Ru(bpy)2(dcbpy)NHS were successfully synthesized and labeled on the IgG. Furthermore, on the formation of an antibody-antigen immunocomplex, biotin-streptavidin system and on the basis of the strong and stable ECL signal, we designed a novel multiple signal amplification of sandwichtype ECLIA for sensitive detection of carcinoembryonic antigen (CEA) antibody. The calibration curve was linear in the range of 1.0–780 ng mL–1 with a detection limit of 0.28 ng mL–1 (σ = 3) and relative standard deviation of 3.9% (n = 6). The results indicated that the new sandwich-type ECLIA provide several advantages, such as high sensitivity, good selectivity, and wide linear range. This technique can be used in detection of anti-CEA as well as of other tumor markers.