Saadi Bayat

Various polar tripeptides as asymmetric organocatalyst in direct aldol reactions in aqueous media

A series of tripeptide organocatalysts containing a secondary amine group and two amino acids with polar side chain units were developed and evaluated in the direct asymmetric intermolecular aldol reaction of 4-nitrobenzaldehyde and cyclohexanone. The effectiveness of short polar peptides as asymmetric catalysts in aldol reactions to attain high yields of enantio- and diastereoselective isomers were investigated. In a comparison, glutamic acid and histidine produced higher % ee and yields when they were applied as the second amino acid in short trimeric peptides. These short polar peptides were found to be efficient organocatalysts for the asymmetric aldol addition reaction in aqueous media.

Rational design of mimetic peptides based on aldo-ketoreductase enzyme as asymmetric organocatalysts in aldol reactions

Peptides as a kind of important chiral scaffold are broadly identified for their obvious advantages, diverse structures and accessibility. Based on promiscuous aldo-keto-reductase enzymes, several mimetic peptides were designed which were synthesized and tested as multifunctional organocatalysts in direct asymmetric aldol reactions. The corresponding aldol products were produced with high yields (up to 97%) and excellent diastereoselectivities (up to 99/1) and enantioselectivities (>98%) under mild reaction selectivity and enantioselectivity. The secondary structures of peptide catalysts provide an understanding of their mechanism.

Synthesis and in vitro bioactivity evaluation of new glucose and xylitol ester derivatives of 5-aminosalicylic acid

New glucose and xylitol esters of 5-amino salicylic acid (5-ASA) were synthesized followed by evaluation of their in vitro antimicrobial, anti-cancer and anti-inflammatory activities. The results of the antimicrobial activity assessment revealed that the new final esters were more effective against Gram-negative as well as Gram-positive bacteria than the original drug. Furthermore, the new final products were confirmed by a cytotoxicity assay over HT-29 and 3T3 cell lines to be less toxic for normal cells compared to the initial drug. On the other hand, however, their suppressive effect against cancerous cells was somewhat lower. Meanwhile, the anti-inflammatory activity assay over a RAW264.7 macrophage cell line demonstrated that the NO inhibition activity of the conjugated drug to the previously mentioned saccharides, especially to glucose, has slightly improved compared to the non-conjugated drug. Finally, in silico screening was also performed in order to predict the potential interactions and binding energy of the novel products against cyclooxygenase (COX-1/COX-2) and lipoxygenase (5-LOX) proteins. Findings indicated that the new products had greater hydrogen bonds and binding affinities with the active sites of proteins towards 5-ASA.

A Simple Add-and-Display Method for Immobilisation of Cancer Drug on His-tagged Virus-like Nanoparticles for Controlled Drug Delivery

AbstractpH-responsive virus-like nanoparticles (VLNPs) hold promising potential as drug delivery systems for cancer therapy. In the present study, hepatitis B virus (HBV) VLNPs harbouring His-tags were used to display doxorubicin (DOX) via nitrilotriacetic acid (NTA) conjugation. The His-tags served as pH-responsive nanojoints which released DOX from VLNPs in a controlled manner. The His-tagged VLNPs conjugated non-covalently with NTA-DOX, and cross-linked with folic acid (FA) were able to specifically target and deliver the DOX into ovarian cancer cells via folate receptor (FR)-mediated endocytosis. The cytotoxicity and cellular uptake results revealed that the His-tagged VLNPs significantly increased the accumulation of DOX in the ovarian cancer cells and enhanced the uptake of DOX, which improved anti-tumour effects. This study demonstrated that NTA-DOX can be easily displayed on His-tagged VLNPs by a simple Add-and-Display step with high coupling efficiency and the drug was only released at low pH in a controlled manner. This approach facilitates specific attachment of any drug molecule on His-tagged VLNPs at the very mild conditions without changing the biological structure and native conformation of the VLNPs.

Design of a Simple Organocatalysts for Asymmetric Direct Aldol Reactions in Aqueous Medium

AbstractA novel and simple organocatalyst derived from proline was designed, synthesized and tested for its catalytic potential in a direct asymmetric aldol reaction between 4-nitrobenzaldehyde and cychlohexanone in aqueous media. The relatively inexpensive and safe solvent, water stabilized the transition state, and increased reactivity and selectivity of catalyst. The diastereo- and enantio-selective products of the reaction were obtained in excellent yields. Graphical Abstract

Novel Octapeptide as an Asymmetric Catalyst for Michael Reaction in Aqueous Media

Abstract In this work, three forms of a novel octapeptide have been evaluated as asymmetric catalysts for the Michael reaction. Low quantity catalyst loading, ecofriendly solvents, and reusability of organocatalyst successfully applied to attain excellent yields and moderate enantioselectivities in the Michael reaction. [Supplementary materials are available for this article. Go to the publishers online edition of Synthetic Communications® for the following free supplemental resources: Full experimental and spectral details.] GRAPHICAL ABSTRACT

Hypocholesterolemic activity of monascus fermented product in the absence of monacolins with partial purification for functional food applications.

Hypercholesterolemia is one of the most common chronic diseases in human. Along with chemical therapy traditional medication is used as hypocholesterolemic remedy, however, with unfavorable side effects. Recently, Monascus fermented product (MFP) has become a popular hypocholesterolemic natural supplement. In the present study, the hypocholesterolemic activity of Monascus purpureus FTC5391 fermented product ethanolic extract (MFPe) was investigated in hypercholesterolemic rats. Results showed that MFPe not only reduced the serum total cholesterol (TC), LDL-C, TG concentration, and TC/HDL-C ratio but also increased the HDL-C. Further, solid phase extraction (SPE) was carried out to obtain the hypocholesterolemic bioactive fraction. The high polar fraction of SPE increased the HDL-C (42%) and decreased the TC (53.3%), LDL-C (47%), and TG (50.7%) levels as well as TC/HDL-C ratio (69.1%) in serum. The GC-MS results of the active fraction revealed two main compounds, isosorbide and erythritol, which act as coronary vasodilator compounds.

Synthesis, bioactivity evaluation, and docking study of 5-aminosalicylic acid’s fatty acid derivatives

Some new oleic acid, linoleic acid, lauric acid derivatives of 5-aminosalicylic acid were produced in order to enhance bioactivity properties of 5-aminosalicylic acid. All new compounds’ structures were confirmed by spectroscopic methods. Moreover, in vitro antibacterial, anticancer, and anti-inflammatory activities of new synthesized compounds were investigated. Antibacterial activity was studied against pathogenic Gram-negative bacteria, Escherichia coli and Gram-positive bacteria, Staphylococcus aureus via disc diffusion method. Additionally, all derivatives’ anti-inflammatory activity were evaluated through NO suppression assay using interferon gamma (IFN-γ)/lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Furthermore, in vitro cytotoxicity assay was probed using MTT test against 3T3 and HT-29 cell lines. In another effort, docking studies were performed to predict the possible interactions and binding energy of new compounds against cyclooxygenase (COX-1/COX-2) and lipoxygenase (5-LOX) proteins. In conclusion, all new compounds exhibited moderate to better bioactivity improvements in comparison with parent drug. Also study of interactions between the new derivatives with active sites of proteins presented greater binding affinities than 5-aminosalicylic acid.Graphical abstract

Synthesis and in-vitro bioactivity evaluation of new galactose and fructose ester derivatives of 5-aminosalicylic acid.

Inflammatory bowel disease (IBD) is the main risk factor for developing colorectal cancer which is common in patients of all ages. 5‐Aminosalicylic acid (5‐ASA), structurally related to the salicylates, is highly active in the treatment of IBD with minor side effects. In this study, the synthesis of galactose and fructose esters of 5‐ASA was planned to evaluate the role of glycoconjugation on the bioactivity of the parent drug. The antibacterial activity of the new compounds were evaluated against two Gram‐negative and two Gram‐positive species of bacteria, with a notable effect observed against Staphylococcus aureus and Escherichia coli in comparisons with the 5‐ASA. Cytotoxicity testing over HT‐29 and 3T3 cell lines indicated that the toxicity of the new products against normal cells was significantly reduced compared with the original drug, whereas their activity against cancerous cells was slightly decreased. The anti‐inflammatory activity test in RAW264.7 macrophage cells indicated that the inhibition of nitric oxide by both of the monosaccharide conjugated derivatives was slightly improved in comparison with the non‐conjugated drug.

Enantioselectivity investigation of short polar peptides with different positions in the Michael reaction

Abstract This work reports the effectiveness of short polar peptides as asymmetric catalysts in Michael reactions to attain good yields of enantio- and diastereoselective isomers. In a comparison, glutamic acid and histidine produced greater ee and yields when they were applied as the second amino acid in short trimeric peptides. These short polar peptides were found to be efficient organocatalysts for the asymmetric Michael addition reaction in water. Supplemental materials are available for this article. Go to the publishers online edition of Synthetic Communications® to view the free supplemental file. GRAPHICAL ABSTRACT