Synthesis and Pharmacological Profile of Benzimidazoles

Benzimidazoles are a class of heterocyclic, aromatic compounds which share a fundamental structural characteristic of six-membered benzene fused to five-membered imidazole moiety. Molecules having benzimidazole motifs showed promising application in biological and clinical studies. Nowadays it is a moiety of choice which possesses many pharmacological properties extensively explored with a potent inhibitor of various enzymes involved in a wide range of therapeutic uses which are antidiabetic, anticancer, antimicrobial, antiparasitic, analgesics, antiviral, and antihistamine, as well as used in cardiovascular disease, neurology, endocrinology, ophthalmology, and more. The increased interest for benzimidazole compounds has been due to their excellent properties, like increased stability, bioavailability, and significant biological activity. This book chapter mainly discussed recent synthetic methods developed for the benzimidazole derivatives and their pharmacological properties exemplified on several derivatives

CuI-NPs catalyzed mechanochemical-assisted N-Boc protection of organic amines

A simple, solvent-free, faster and mechanochemical approach for the N-tert-butoxycarbonylation of amines catalyzed by copper iodide nanoparticles as a recyclable catalyst is described. The advantages of this method are simplicity, shorter reaction time (5–15 min), a cost-effective catalyst, and excellent product isolation (82-92%). N-Boc protection of various structurally diverse aliphatic, aromatic, and heterocyclic amines have been carried out with (Boc)2O with 10 mol% catalyst under pestle mortar grinding under solvent-free conditions. The catalyst possesses distinct advantages, ease of handling as well as removal, cleaner reactions, high activity, and environmentally benign. The final product has been characterised by various spectroscopic techniques

Prenylation of Natural Products: An Overview

Natural products with varied functional attributes are available in large abundance in nature. Nature has been an infinite repository of resources leading to drug development, discovery of novel chemicals, pharmacophores, and several invaluable bioactive agents. Natural products play a critical role in modern drug development, especially for antibacterial and antitumor agents. Their varied chemical structure, composition, solubility, and synthetic pathways bestow upon them a high level of diversity. Prenylation is a covalent addition of hydrophobic moieties to proteins or any other chemical compounds. Generally, the hydrophobic moieties are farnesyl or geranylgeranyl isoprenyl groups. Prenylation of flavonoids, alkaloids, terpernoids, etc., leads to gain of varied functionalities to the natural products in addition to the already existing functions. The ever-increasing need for the discovery of new drugs finds a new avenue through the prenylation of natural products. Cell-free synthesis of the prenylated natural products can be seen as a new alternative for the natural synthesis, which warrants time-consuming isolation and purification techniques

Prenylated Proteins: Structural Diversity and Functions

The cell membranes consist of lipid bilayers that are semipermeable. The semipermeable nature enables the cell membranes to regulate the transport of materials entering and exiting the cell. Apart from providing protection and a fixed environment to the cell, the cell membrane has several functions. The covalently linked proteins to lipids on the surface of the cell membranes are the Lipid-anchored proteins. The function of the protein to which the lipid is attached depends on the type of the lipid. Prenylated proteins, fatty acylated proteins, and glycosylphosphatidylinositol-linked proteins (GPI) are the three main types of lipid-anchored proteins on the cell membrane. In particular, the prenylated proteins are very important for cell growth, differentiation, and morphology. The dynamic interaction of prenylated proteins with the cell membrane is important for their signaling functions and is often deregulated in disease processes, such as cancer. An understanding of the prenylated proteins and their mechanisms is important for drug development efforts to combat cancer

Zinc dust catalysed efficient synthesis of 4-arylidene-2-phenyl-5(4H)-oxazolones

A straight forward synthesis of 4-arylidene-2-phenyl-5(4H)-oxazolones (also called azlactones) by the condensation of arylaldehyde with hippuric acid in the presence of acetic anhydride and zinc dust as aheterogeneous catalyst is described. The reaction proceeds rapidly, does not require any additives and has a significantly shorter reaction rate. In the present method, aromatic aldehydes and hippuric acid have been successfully applied to synthesize various substituted azlactones in good to excellent yields. The final product has been characterised by FT-IR, 1H and 13C NMR, and mass spectrometry.

Multifunctional Bionanocomposite Films Based on Chitosan/Polyvinyl Alcohol with ZnO NPs and <i>Carissa carandas</i> Extract Anthocyanin for Smart Packaging Materials

The present work describes chitosan (CS) and polyvinyl alcohol (PVA) films incorporated with the natural anthocyanin derived from Carissa carandas and fabricated with ZnO NPs. They showed pH sensitivity, antioxidant activity, and cell viable properties. Anthocyanin, ZnO NPs, and anthocyanin-ZnO NPs fabricated on the CS/PVA matrix significantly increased mechanical resistance and reduced moisture contents (MCs) and water vapor permeability (WVP) of the films significantly. The inclusion of anthocyanin-ZnO NPs significantly affected the cell viability of the prepared film (P > 0.05). Optical characteristics suitable for food packaging applications were exhibited by the prepared films. Additionally, in various pH buffer solutions, the developed films showed noticeable color changes and could be visualized. This property of the film could be employed for fish packaging to monitor freshness, with the film turning from colorless to yellow. It could efficiently monitor the degree of the fish fillet deterioration. Moreover, the prepared CPAZ films showed very good antioxidant activity and cell viability and emerged as a smart intelligent film for food packaging industries

Pregabalin peptides: conformational comparison of gamma(3)- and gamma(4)-substituted gamma-amino acids in alpha gamma alpha alpha alpha pentapeptides

Gamma-aminobutyric acid (GABA, gammaAbu), an unsubstituted gamma-amino acid, is an important inhibitory neurotransmitter in the mammalian brain. The role of GABA in the treatment of epilepsy has triggered a great deal of interest in substituted gamma-amino acids, which may serve as GABA analogs, acting as inhibitors of GABA aminotransferase. Pregabalin (Pgn), a well-known antiepileptic drug, is also a beta-substituted gamma3-amino acid. Pregabalin and gamma4Leu, an isomer of the pregabalin (Pgn) residue, both carrying the same isobutyryl group in the side chain, were introduced in the present study to have a comparison of their respective conformational differences as well as their role in influencing the overall conformation of the peptides, they are inserted in. Two alpha-gamma-alpha-alpha-alpha hybrid pentapeptides were designed that contain Aib-Pgn and Aib-gamma4Leu segments at the N terminus. The study provides a detailed analysis of the conformational properties and non-covalent interactions observed in the crystal structures of two polymorphs of the pentapeptide monohydrate, Boc-Aib-(S)Pgn-Leu-Phe-Val-OMe (C38H63N5O8 center dot H2O) and the isomeric pentapeptide, Boc-Aib-gamma4(R)Leu-Leu-Phe-Val-OMe (C38H63N5O8), obtained from single crystal X-ray diffraction experiments

An Agro-Waste Catalyzed Facile Synthesis of 1<i>H-</i>Pyrazolo[1,2-b]Phthalazine-5,10-Dione Derivatives: Evaluation of Antioxidant and Electrochemical Studies

Rapid and inexpensive one-pot multicomponent synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione through a condensation reaction of aryl aldehyde, malononitrile or ethyl cyanoacetate and phthalhydrazide catalyzed by water extract of papaya bark ash (WEPBA) solvent medium under microwave irradiation is described. The catalytic medium is used environmentally friendly, and provides several benefits of being simple, inexpensive, high yield, simple work-up and not required hazardous solvent for the reaction. Some of the selected derivatives were characterized by FT-IR, 1H-, and 13C-NMR, and mass spectrometry techniques. The oxidation-reduction properties of the synthesized compounds (4b, 4e, 4f, 4i, and 4k and 6f, 6g, 6h, 6i, and 6j) were studied using cyclic voltammetry (CV). The voltammetry peak current for the oxidation-reduction of the compounds examined at different scan rates. Further, some of the selected 1H-pyrazolo[1,2-b]phthalazine-5,10-dione derivatives were evaluated in vitro antioxidant activity using DPPH assay method. The result appears that, compounds 4b, 4e, 4i, 6f, 6g, and 6h possess significant antioxidant properties in comparison with the ascorbic acid reference.</p

Disulfide Sensitivity in the Env Protein Underlies Lytic Inactivation of HIV‑1 by Peptide Triazole Thiols

We investigated the mode of action underlying lytic inactivation of HIV-1 virions by peptide triazole thiol (PTT), in particular the relationship between gp120 disulfides and the C-terminal cysteine-SH required for virolysis. Obligate PTT dimer obtained by PTT SH cross-linking and PTTs with serially truncated linkers between pharmacophore isoleucine–ferrocenyltriazole-proline–tryptophan and cysteine-SH were synthesized. PTT variants showed loss of lytic activity but not binding and infection inhibition upon SH blockade. A disproportionate loss of lysis activity vs binding and infection inhibition was observed upon linker truncation. Molecular docking of PTT onto gp120 argued that, with sufficient linker length, the peptide SH could approach and disrupt several alternative gp120 disulfides. Inhibition of lysis by gp120 mAb 2G12, which binds at the base of the V3 loop, as well as disulfide mutational effects, argued that PTT-induced disruption of the gp120 disulfide cluster at the base of the V3 loop is an important step in lytic inactivation of HIV-1. Further, PTT-induced lysis was enhanced after treating virus with reducing agents dithiothreitol and tris (2-carboxyethyl)­phosphine. Overall, the results are consistent with the view that the binding of PTT positions the peptide SH group to interfere with conserved disulfides clustered proximal to the CD4 binding site in gp120, leading to disulfide exchange in gp120 and possibly gp41, rearrangement of the Env spike, and ultimately disruption of the viral membrane. The dependence of lysis activity on thiol–disulfide interaction may be related to intrinsic disulfide exchange susceptibility in gp120 that has been reported previously to play a role in HIV-1 cell infection