Efficacy of a Standardized Turmeric Extract Comprised of 70% Bisdemothoxy-Curcumin (REVERC3) Against LPS-Induced Inflammation in RAW264.7 Cells and Carrageenan-Induced Paw Edema.

OBJECTIVE: It is well known that regular turmeric extract with 95% curcuminoid is comprised of curcumin (70.07%), desmethoxycurcumin (20.28%), and bisdemethoxycurcumin (BDMC) (3.63%). In the current study for the first time, we have enriched about 3% of bisdemethoxycurcumin (BDMC) to 70% as well as named it as REVERC3 and compared anti-inflammatory activity with regular turmeric extract using in vitro and in vivo models of inflammation. METHODS: To reveal the potential anti-inflammatory mechanism of action, we investigated nitric oxide (NO) scavenging, xanthine oxidase, and lipoxygenase inhibitory activity, further determined the level of pro-inflammatory cytokines, such as interleukin 6 (IL-6), tumor necrosis factor (TNF-α) and major inflammatory mediators like cyclooxygenase (COX-2) and inducible nitric oxide synthase (iNOS), inhibition in lipopolysaccharide (LPS) induced inflammation in RAW macrophage cells. In the other hand, a carrageenan-stimulated inflammatory rat model was carried out. RESULTS: Our study findings exhibited a significant anti-inflammatory activity of REVERC3 together with nitric oxide (NO), xanthine oxidase, and lipoxygenase inhibition. Further, we attenuated the levels of cyclooxygenase (COX-2), inducible nitric oxide synthase (iNOS), interleukin (IL-6) and tumor necrosis factor (TNF-α) expressions in the LPS-elicited RAW macrophage cells. REVERC3 showed a potential anti-inflammatory activity by inhibiting carrageenan induced paw edema after 4 hr at the dose of 100mg/kg body weight. CONCLUSION: Thus, our findings collectively indicated that the REVERC3 could efficiently inhibit inflammation compared to regular turmeric extract. Since bisdemethoxycurcumin is a stable molecule it could be effectively used in the applications of health care and the nutraceutical industry, indeed which deserves further investigations.

Directing peptide conformation with centrally positioned pre-organized dipeptide segments: studies of a 12-residue helix and ß-hairpin.

Secondary structure formation in oligopeptides can be induced by short nucleating segments with a high propensity to form hydrogen bonded turn conformations. Type I/III turns facilitate helical folding while type II'/I' turns favour hairpin formation. This principle is experimentally verified by studies of two designed dodecapeptides, Boc-Val-Phe-Leu-Phe-Val-Aib-Aib-Val-Phe-Leu-Phe-Val-OMe 1 and Boc-Val-Phe-Leu-Phe-Val-(D)Pro-(L)Pro-Val-Phe-Leu-Phe-Val-OMe 2. The N- and C-terminal flanking pentapeptide sequences in both cases are identical. Peptide 1 adopts a largely α-helical conformation in crystals, with a small 310 helical segment at the N-terminus. The overall helical fold is maintained in methanol solution as evidenced by NMR studies. Peptide 2 adopts an antiparallel ß-hairpin conformation stabilized by 6 interstrand hydrogen bonds. Key nuclear Overhauser effects (NOEs) provide evidence for the antiparallel ß-hairpin structure. Aromatic proton chemical shifts provide a clear distinction between the conformation of peptides 1 (helical) and 2 (ß-hairpin). The proximity of facing aromatic residues positioned at non-hydrogen bonding positions in the hairpin results in extensively ring current shifted proton resonances in peptide 2.

Helix and hairpin nucleation in short peptides using centrally positioned conformationally constrained dipeptide segments.

The effect of incorporation of a centrally positioned Ac(6)c-Xxx segment where Xxx = (L)Val/(D)Val into a host oligopeptide composed of l-amino acid residues has been investigated. Studies of four designed octapeptides Boc-Leu-Phe-Val-Ac(6)c-Xxx-Leu-Phe-Val-OMe (Xxx = (D)Val 1, (L)Val 2) Boc-Leu-Val-Val-Ac(6)c-Xxx-Leu-Val-Val-OMe (Xxx = (D)Val 3, (L)Val 4) are reported. Diagnostic nuclear Overhouse effects characteristic of hairpin conformations are observed for Xxx = (D)Val peptides (1 and 3) while continuous helical conformation characterized by sequential N(i)H ↔ N(i+1)H NOEs are favored for Xxx = (L)Val peptides (2 and 4) in methanol solutions. Temperature co-efficient of NH chemical shifts are in agreement with distinctly different conformational preferences upon changing the configuration of the residue at position 5. Crystal structures of peptides 2 and 4 (Xxx = (L)Val) establish helical conformations in the solid state, in agreement with the structures deduced from NMR data. The results support the design principle that centrally positioned type I ß-turns may be used to nucleate helices in short peptides, while type I'ß-turns can facilitate folding into ß-hairpins.

Synthesis and antileukemic activity of novel 2-(4-(2,4-dimethoxybenzoyl)phenoxy)-1-(4-(3-(piperidin-4-yl)propyl)piperidin-1-yl)ethanone derivatives.

A series of novel 2-(4-(2,4-dimethoxybenzoyl)phenoxy)-1-(4-(3-(piperidin-4-yl)propyl) piperidin-1-yl)ethanone derivatives 9(a-e) and 10(a-g) were synthesized and characterized by (1) H NMR, IR, mass spectral, and elemental analysis. These novel compounds were evaluated for their antileukemic activity against two human leukemic cell lines (K562 and CEM) by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay. Some of the tested compounds showed good antiproliferative activity with IC(50) values ranging from 1.6 to 8.0 µm. Compound 9c, 9e, and 10f with an electron-withdrawing halogen substituent at the para position on the phenyl ring showed excellent in vitro potency against tested human leukemia cells (K562 and CEM).

Synthesis and antileukemic activity of novel 4-(3-(piperidin-4-yl) propyl)piperidine derivatives.

To explore the anticancer effect associated with the piperidine framework, several (substituted phenyl) {4-[3-(piperidin-4-yl)propyl]piperidin-1-yl} methanone derivatives 3(a-i) were synthesized. Variation in the functional group at N-terminal of the piperidine led to a set of compounds bearing amide moiety. Their chemical structures were confirmed by (1) H NMR, IR and mass spectra analysis. Among these, compounds 3a, 3d and 3e were endowed with antiproliferative activity. The most active compound among this series was 3a with nitro and fluoro substitution on the phenyl ring of aryl carboxamide moiety, which inhibited the growth of human leukemia cells (K562 and Reh) at low concentration. Comparison with other derivative (3h) results shown by LDH assay, cell cycle analysis and DNA fragmentation suggested that 3a is more potent to induce apoptosis.

Synthesis, characterization and in-vitro antiproliferative effects of novel 5-amino pyrazole derivatives against breast cancer cell lines.

In search of synthetic chemotherapeutic substances capable of inhibiting, retarding, or reversing the process of multistage carcinogenesis, we synthesised a series of novel 1-(4-methoxybenzyl)-3-cyclopropyl-1H-pyrazol-5-amine derivatives 9(a-h) by a nucleophilic substitution reaction and characterized by (1)H and (13)C nuclear magnetic resonance (NMR), liquid chromatography mass spectrometry (LC/MS), Fourier-transform infrared (FTIR), and elemental analysis. These novel compounds were evaluated for their efficacy in inhibiting VERO normal and MCF-7 breast cancer cells proliferation by trypan blue exclusion assay, MTT assay, [(3)H] thymidine incorporation assay and DNA fragmentation analysis. Among the series, some compounds exhibited interesting growth inhibitory effects against cell lines. From the Structure-Activity Relationship studies, it has been revealed that, both novel patented compounds and therapeutic protocols of N-terminal pyrazole ring structures play key role in the antiproliferative activity.