Shijun Ren

Bio: Shijun Ren is an academic researcher from University of Southern California. The author has contributed to research in topics: Cyclin-dependent kinase & Reductase. The author has an hindex of 11, co-authored 15 publications receiving 1033 citations.

Synthesis, Biological Evaluation, and Quantitative Structure−Activity Relationship Analysis of New Schiff Bases of Hydroxysemicarbazide as Potential Antitumor Agents†

Abstract: Thirty Schiff bases of hydroxysemicarbazide (Ar−CHNNHCONHOH) have been synthesized and tested against L1210 murine leukemia cells. The IC50 values were found to be in a range from 2.7 × 10-6 to 9.4 × 10-4 M. A total of 17 out of the 30 compounds had higher inhibitory activities than hydroxyurea (an anticancer drug currently used for the treatment of melanoma, leukemia, and ovarian cancer) against L1210 cells. Six compounds with IC50 values in micromolar range were 11- to 30-fold more potent than hydroxyurea (IC50 = 8.2 × 10-5 M). The partition coefficient (log P) and ionization constants (pKa) of a model compound [1-(3-trifluoromethylbenzylidene)-4-hydroxysemicarbazide, 1] were measured by the shake-flask method, and the measured log P was used to derive Hansch−Fujita π constant of −CHNNHCONHOH. On the basis of the newly derived π and those of other moieties, the partition coefficients (SlogP) of the other 29 compounds were calculated by the summation of π values. Quantitative structure−activity relations...

Antiviral tannins from two Phyllanthus species.

Abstract: Seven ellagitannins isolated from Phyllanthus myrtifolius and P. urinaria (Euphorbiaceae) have been shown, for the first time, to be active against Epstein-Barr virus DNA polymerase (EBV-DP) at the microM level. All these compounds have the same moiety of a corilagin, and differ from each other by different substitutions at C-2 and C-4 of the glucose core. SAR analysis and molecular modeling reveal that the essential pharmacophore of these tannins resides in the corilagin moiety. The outer complex carboxylic acid moieties appear to act only as auxopharmacore.

Caco-2 cell permeability vs human gastrointestinal absorption: QSPR analysis.

Abstract: The aim of this study is to elucidate quantitative structure-permeability relationship (QSPR) of various organic molecules through Caco-2 cells, and to ascertain the relationship between gastrointestinal (GI) absorption in humans and Caco-2 cell permeability. Caco-2 cell permeability and human GI absorption data were obtained from the literature. The maximum hydrogen bond-forming capacity corrected for intra-molecular H-bonding (H b c ) and Lien’s QSAR model were used in this study. The latest CQSAR software was utilized in calculating the logarithm of partition coefficient in octanol/water (Clog P) and in deriving all regression equations. For 51 compounds, a significant correlation was obtained between Caco-2 cell permeability (log Pcaco-2)and Hbc, octanol/PBS (phosphate buffered saline, pH 7.4) distribution coefficient (log Doct), log MW and an indicator variable (I) for the charge, with a correlation coefficient of 0.797. When these compounds were divided into three subgroups, namely neutral, cationic and anionic compounds, much better correlations (r = 0.968, 0.915 and 0.931, respectively) were obtained using different combinations of various physicochemical parameters. A plot of human GI absorption vs. Caco-2 cell permeability obtained from different laboratories reveals that Caco-2 cell permeability cannot be used to precisely predict human GI absorption for compounds with Pcaco-2 below 5 x 10-6cm/s, due to interlaboratory and experimental variabilities, and the lack of a simple correlation between human GI absorption and Caco-2 cell permeability. Caco-2 cell permeability may be estimated from the structures of drug molecules using the above-mentioned physicochemical parameters. In general, for compounds with Pcaco-2)above 5 x 10-6cm/s, human GI absorption ranges from 50 to 100%. This is generally acceptable for development into oral dosage form. For the compounds with Pcaco-2)below 5 x 10-6cm/s, careful interpretation of caco- 2 cell permeability and use of internal standard for comparison are recommended. Otherwise, good drug candidates may be excluded due to incorrectly predicted poor absorption.

Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships.

Abstract: Flavonoids are a class of secondary plant phenolics with significant antioxidant and chelating properties. In the human diet, they are most concentrated in fruits, vegetables, wines, teas and cocoa. Their cardioprotective effects stem from the ability to inhibit lipid peroxidation, chelate redox-active metals, and attenuate other processes involving reactive oxygen species. Flavonoids occur in foods primarily as glycosides and polymers that are degraded to variable extents in the digestive tract. Although metabolism of these compounds remains elusive, enteric absorption occurs sufficiently to reduce plasma indices of oxidant status. The propensity of a flavonoid to inhibit free-radical mediated events is governed by its chemical structure. Since these compounds are based on the flavan nucleus, the number, positions, and types of substitutions influence radical scavenging and chelating activity. The diversity and multiple mechanisms of flavonoid action, together with the numerous methods of initiation, detection and measurement of oxidative processes in vitro and in vivo offer plausible explanations for existing discrepancies in structure-activity relationships. Despite some inconsistent lines of evidence, several structure-activity relationships are well established in vitro. Multiple hydroxyl groups confer upon the molecule substantial antioxidant, chelating and prooxidant activity. Methoxy groups introduce unfavorable steric effects and increase lipophilicity and membrane partitioning. A double bond and carbonyl function in the heterocycle or polymerization of the nuclear structure increases activity by affording a more stable flavonoid radical through conjugation and electron delocalization. Further investigation of the metabolism of these phytochemicals is justified to extend structure-activity relationships (SAR) to preventive and therapeutic nutritional strategies.

DIETARY FLAVONOIDS: Bioavailability, Metabolic Effects, and Safety

Abstract: ▪ Abstract Flavonoids comprise the most common group of plant polyphenols and provide much of the flavor and color to fruits and vegetables. More than 5000 different flavonoids have been described. The six major subclasses of flavonoids include the flavones (e.g., apigenin, luteolin), flavonols (e.g., quercetin, myricetin), flavanones (e.g., naringenin, hesperidin), catechins or flavanols (e.g., epicatechin, gallocatechin), anthocyanidins (e.g., cyanidin, pelargonidin), and isoflavones (e.g., genistein, daidzein). Most of the flavonoids present in plants are attached to sugars (glycosides), although occasionally they are found as aglycones. Interest in the possible health benefits of flavonoids has increased owing to their potent antioxidant and free-radical scavenging activities observed in vitro. There is growing evidence from human feeding studies that the absorption and bioavailability of specific flavonoids is much higher than originally believed. However, epidemiologic studies exploring the role of ...

Chemistry and Biology Of Multicomponent Reactions

Abstract: Multicomponent reactions (MCRs) are one-pot reactions employing more than two starting materials, e.g. 3, 4, … 7, where most of the atoms of the starting materials are incorporated in the final product.1 Several descriptive tags are regularly attached to MCRs (Fig. 1): they are atom economic, e.g. the majority if not all of the atoms of the starting materials are incorporated in the product; they are efficient, e.g. they efficiently yield the product since the product is formed in one-step instead of multiple sequential steps; they are convergent, e.g. several starting materials combine in one reaction to form the product; they exhibit a very high bond-forming-index (BFI), e.g. several non-hydrogen atom bonds are formed in one synthetic transformation.2 Therefore MCRs are often a useful alternative to sequential multistep synthesis. Open in a separate window Figure 1 Above: multistep syntheses can be divergent (sequential) or convergent; below: in analogy MCR reactions are convergent and one or two component reactions are divergent or less convergent.