Exploring the Binding Affinity of Novel Syringic Acid Analogues and Critical Determinants of Selectivity as Potent Proteasome Inhibitors.

Syringic acid, a known plant phenolic compound and its analogues are known to possess high proteasome inhibitory activity. In the current work, we describe synthesis, characterization, DFT, docking of syringic acid (SA) and analogues (SAA1 and SAA2) and biological effects were studied. Syringic acid and its analogues were docked for the first time with the crystal structures of ß5 proteasome of diverse eukaryotic organisms. Among all proteasomes, the humanoid proteasome showed the highest degree of docking conformation and low inhibition constant (Ki). SAA2 specifically displayed binding to the N-terminal Thr1 residue in the S1 pocket of Mus musculus ß5 proteasome along with threonine, lysine and arginine; conventionally involved major amino acid residues in ligand binding. The geometrical properties (B3LYP/6- 31g (d, p)) and electrostatic potentials of molecules were computed using DFT calculations. A detailed molecular picture of the compounds and its interactions was obtained from NBO analysis. SA-analogues elucidated potent antioxidant activities and good antibacterial activity. In-vitro DNA binding studies revealed that all molecules had strong binding at the major groove of dsDNA. In the view of medical applicability, proteasome inhibition is an important therapeutic strategy for various types of cancers. Therefore, current discoveries may encourage the rational design and development of new chemical entities of syringic acid based chemotherapeutics.

Nutrigenetic screening strains of the mulberry silkworm, Bombyx mori, for nutritional efficiency.

The activity of sericulture is declining due the reduction of mulberry production area in sericulture practicing countries lead to adverse effects on silkworm rearing and cocoon production. Screening for nutrigenetic traits in silkworm, Bombyx mori L. (Lepidoptera: Bombycidae) is an essential prerequisite for better understanding and development of nutritionally efficient breeds/hybrids, which show less food consumption with higher efficiency conversion. The aim of this study was to identify nutritionally efficient polyvoltine silkworm strains using the germplasm breeds RMW(2), RMW(3), RMW(4), RMG(3), RMG(1), RMG(4), RMG(5), RMG(6) and APM(1) as the control. The 1(st) day of 5(th) stage silkworm larvae of polyvoltine strains were subjected to standard gravimetric analysis until spinning for three consecutive generations covering three different seasons on 19 nutrigenetic traits. Highly significant (p ≤ 0.001) differences were found among all nutrigenetic traits of polyvoltine silkworm strains in the experimental groups. The nutritionally efficient polvoltine silkworm strains were resulted by utilizing nutrition consumption index and efficiency of conversion of ingesta/cocoon traits as the index. Higher nutritional efficiency conversions were found in the polyvoltine silkworm strains on efficiency of conversion of ingesta to cocoon and shell than control. Comparatively smaller consumption index, respiration, metabolic rate with superior relative growth rate, and quantum of food ingesta and digesta requisite per gram of cocoon and shell were shown; the lowest amount was in new polyvoltine strains compared to the control. Furthermore, based on the overall nutrigenetic traits utilized as index or 'biomarkers', three polyvoltine silkworm strains (RMG(4), RMW(2), and RMW(3)) were identified as having the potential for nutrition efficiency conversion. The data from the present study advances our knowledge for the development of nutritionally efficient silkworm breeds/hybrids and their effective commercial utilization in the sericulture industry.

Catalysis by molecular iodine: a rapid synthesis of 1,8-dioxo-octahydroxanthenes and their evaluation as potential anticancer agents.

Molecular iodine facilitated the reaction of 5,5-dimethyl-1,3-cyclohexanedione with aromatic aldehydes in iso-propanol affording a variety of 1,8-dioxo-octahydroxanthenes in high yields. Most of the compounds synthesized showed good anti-proliferative properties in vitro against three cancer cell lines and 9-(2-hydroxyphenyl)-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2H)-dione possessing a 2-hydroxy phenyl group at C-9 position was found to be promising. Further structure elaboration of the same compound and the crystal structure analysis and hydrogen bonding patterns of another compound that is, 9-(4-methoxyphenyl)-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2H)-dione prepared by using this methodology is presented.

Novel derivative of benzofuran induces cell death mostly by G2/M cell cycle arrest through p53-dependent pathway but partially by inhibition of NF-kappaB.

The Dracaena resin is widely used in traditional medicine as an anticancer agent, and benzofuran lignan is the active component. In this report, we provide evidence that the synthetic derivative of benzofuran lignan (Benfur) showed antitumor activities. It induced apoptosis in p53-positive cells. Though it inhibited endotoxin-induced nuclear factor kappaB (NF-kappaB) activation in both p53-positive and -negative cells, the activation of caspase 3 was observed in p53-positive cells. It showed partial cell death effect in both p53-positive and -negative cells through inhibition of NF-kappaB. Cell cycle analysis using flow cytometry showed that treatment with this novel benozofuran lignan derivative to Jurkat T-cells, but not U-937 cells, resulted in a G2/M arrest in a dose- and time-dependent manner. It increased amounts of p21, p27, and cyclin B, but not phospho-Rb through p53 nuclear translocation in Jurkat T-cells, but not in U-937 cells. It inhibited amounts of MDM2 (murine double minute 2) by repressing the transcription factor Sp1, which was also proved in silico. It induced cell death in tumor cells, but not in primary T-cells. Overall, our data suggest that Benfur-mediated cell death is partially dependent upon NF-kappaB, but predominantly dependent on p53. Thus, this novel benzofuran lignan derivative can be effective chemopreventive or chemotherapeutic agent against malignant T-cells.

In vitro plant regeneration of fig (Ficus carica L. cv. gular) using apical buds from mature trees.

A reliable procedure for multiple-shoot induction and plantlet regeneration was developed with apical buds collected from 7- to 8-year-old trees of Ficus carica L. using Murashige and Skoog's (MS) medium supplemented with 2.0 mg/l 6-benzylaminopurine and 0.2 mg/l 1-naphthaleneacetic acid. The in-vitro-regenerated shoots were further multiplied on MS medium supplemented with 2.0 mg/l 6-benzylaminopurine and 0.2 mg/l 1-naphthaleneacetic acid and an average multiplication rate of four per subculture was established with 90% success. Excised shoots were rooted in liquid half strength MS medium supplemented with 2.0 mg/l indole-3-butyric acid and 0.2% activated charcoal. Regenerated plantlets were successfully established in soil, with a success rate of 68%.