Extendable stapling of unprotected peptides by crosslinking two amines with o-phthalaldehyde

Peptide modification methods that do not rely on the cysteine residue are underdeveloped, and their development could greatly expand the current toolbox for peptide chemistry. During the course of preliminary investigations into the classical ortho-phthalaldehyde (OPA)-amine-thiol condensation reaction, we found that in the absence of thiol, OPA readily condenses with two primary alkyl amines to form a class of underexplored isoindolin-1-imine compounds under mild aqueous conditions. From the intramolecular version of this OPA-2amines reaction, an efficient and selective methodology using mild reaction conditions has been developed for stapling unprotected peptides via crosslinking of two amino groups in both an end-to-side and side-to-side fashion. The stapling method is superfast and broadly applicable for various peptide substrates with the reacting amino groups separated by a wide range of different amino acid units. The macrocyclization reactions of selected substrates are completed within 10 seconds at 5 mM concentration and within 2 minutes at 50 μM concentration. Importantly, the resulting cyclized peptides with an isoindolinimine linkage can be extended in a one-pot sequential addition manner with several different electron-deficient π electrophiles, thereby generating more complex structures.

Synthesis and Biological Investigation of Bile Acid-Paclitaxel Hybrids

Chenodeoxycholic acid and ursodeoxycholic acid (CDCA and UDCA, respectively) have been conjugated with paclitaxel (PTX) anticancer drugs through a high-yield condensation reaction. Bile acid-PTX hybrids (BA-PTX) have been investigated for their pro-apoptotic activity towards a selection of cancer cell lines as well as healthy fibroblast cells. Chenodeoxycholic-PTX hybrid (CDC-PTX) displayed cytotoxicity and cytoselectivity similar to PTX, whereas ursodeoxycholic-PTX hybrid (UDC-PTX) displayed some anticancer activity only towards HCT116 colon carcinoma cells. Pacific Blue (PB) conjugated derivatives of CDC-PTX and UDC-PTX (CDC-PTX-PB and UDC-PTX-PB, respectively) were also prepared via a multistep synthesis for evaluating their ability to enter tumor cells. CDC-PTX-PB and UDC-PTX-PB flow cytometry clearly showed that both CDCA and UDCA conjugation to PTX improved its incoming into HCT116 cells, allowing the derivatives to enter the cells up to 99.9%, respect to 35% in the case of PTX. Mean fluorescence intensity analysis of cell populations treated with CDC-PTX-PB and UDC-PTX-PB also suggested that CDC-PTX-PB could have a greater ability to pass the plasmatic membrane than UDC-PTX-PB. Both hybrids showed significant lower toxicity with respect to PTX on the NIH-3T3 cell line.

Recent advancement and novel application of organocatalyzed aldol condensation reactions: A comprehensive review

Background: Aldol reactions play an important role in the development of organic synthesis-owing to their critical importance for the forming of carbon-carbon bonds while concurrently one or two chiral centers come into being. In the modern scenario, the Aldol condensation reaction has arisen as perhaps the most significant reaction for the formation of novel medicinal agents exhibits promising pharmacological activities. Objective: The purpose of this study is to present newer synthetic approaches through Aldol condensation reaction for the synthesis of diverse scaffolds to explore the promising various types of biological activities. Methods: Aldol condensation concerns the nucleophilic addition reaction of a ketone enolate to an aldehyde to form aldol or β- hydroxy ketone. Occasionally, the aldol addition product losing water molecule yields an α, β-unsaturated ketone. Results: Results showed that amino acids and all lengths of peptides are utilized as chiral catalysts. As of now, the arrangement of catalysts that have been accounted for is intensely one-sided towards proline. This is to some degree because of its exceptional status among the normally happening amino acids as an auxiliary amine and to its restricted underlying adaptability. Conclusion: The present study thus provides useful insight concerning the promising coherent way for the synthesis of prolinamide analogue of proline, through a direct asymmetric aldol condensation reaction. Thus, the current study summarizes various Aldol condensation reactions for the synthesis of novel agents as well as their promising pharmacological importance.

An efficient 2-aminothiazolesalicylaldehyde Fluorescent Chemosensor for Fe2+ ion Detection and Potential Inhibitor of NUDT5 Signaling Hormone for Breast Cancer Cell and Molecular Keypad Lock Application

A novel thiazole phenol conjugate 2-aminothiazolesalicylaldehyde (receptor1) was designed and synthesized for the first time through a single step process via schiff base condensation reaction. The formation of receptor1 was confirmed by FTIR, 13C NMR and 1H NMR. The receptor1 complexing with various metal ions studied through fluorescence spectroscopy showed its selectivity towards Fe2+ ion following a reverse photo induced electron transfer (PET) process compared to all other potentially competing ions. Furthermore, the receptor1 showed excellent reversibility property on adding EDTA solution. The binding affinity between receptor1-Fe2+ ion was found to be Ka = 2.22x102 M-1 and the sensing affinity of receptor1 towards Fe2+ ion at nanolevel concentration was 33.7x10-9 M which is lower than the detection limit of existing Schiff base. The receptor1 was used to detect Fe2+ ion in different water samples. Using molecular docking the chelating function of ligand (receptor1) was assessed as a potential inhibitor of NUDT5, a silence hormone signaling for breast cancer. The excellent reversibility property is used to construct INHIBIT molecular logic gate.

Emissive Organogel Mediated Construction of Flexible Covalent Organic Polymer for the Separation of Aniline for Water Purification

A flexible covalent organic polymer (COP) has been successfully synthesized via dynamic covalent gel (DCG) formation through imine condensation reaction between 6-hydrazinonicotinic hydrazide hydrate and benzene-1,3,5-tricarboxaldehyde within 7 min under...

Mechanistic investigations on a homogeneous ruthenium Guerbet catalyst in a flow reactor

A mechanistic investigation on the ethanol self-condensation reaction (Guerbet reaction) catalyzed by a bis(pyridylimino)isoindolate Ru(ii) catalyst was performed using a specifically designed continuously-stirred tank reactor (CSTR).

Evaluation of anticancer activities varying ligand’s substituents in Co(II/III)-picolyl phenolate derivatives: Synthesis, characterization, DFT, DNA cleavage and molecular docking studies

The reaction between 2-(pyridine-2-ylmethoxy)-benzaldehyde (L) and various primary amines furnish tridentate (L1 to L3) and tetradentate (L4) chelating ligands. The choice of different primary amines in the condensation reaction incorporates...

Synthesis, Molecular Docking and DFT Studies of Biologically Active N-((3-(4-Nitrophenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)aniline Derivatives

Some biologically active pyrazole clubbed imino molecules have been designed and synthesized from 1-phenyl-3-nitro phenyl-1H- pyrazol-4-carboxaldehyde and substituted aromatic amines via acid catalyzed condensation reaction. All the synthesized molecules were characterized by IR, 1H NMR, 13C NMR and mass spectral techniques. The in vitro antibactericidal property of the synthesized compounds was screened and compared with the results of theoretical molecular docking. Optimization of molecular geometry, DNA binding interaction and FMO analysis were also investigated by computational studies using Gaussian 16 package at B3LYP/6-31G(d,p) level. All the synthesized compounds exhibited moderate to good biological activities both experimentally and theoretically.

Catalytic Synthesis of Methacrolein via the Condensation of Formaldehyde and Propionaldehyde with L-Proline Intercalated Layered Double Hydroxides

Aldol condensation reactions are very important C–C coupling reactions in organic chemistry. In this study, the catalytic performance of layered double hydroxides (LDHs) in the aldol condensation reaction of formaldehyde (FA) and propionaldehyde (PA) was investigated. The MxAl-LDHs (denoted as re-MxAl–LDHs; M = Ca and Mg; X = 2–4), as heterogeneous basic catalysts toward the aldol condensation reaction, were prepared via a two-step procedure. The catalyst exhibited a high PA conversion (82.59%), but the methacrolein (MAL) selectivity was only 36.01% due to the limitation of the alkali-catalyzed mechanism. On this basis, the direct intercalation of L-proline into LDHs also has been investigated. The influences of several operating conditions, including the temperature, reaction time, and substrate content, on the reaction results were systematically studied, and the optimized reaction conditions were obtained. The optimized Mg3Al–Pro-LDHs catalyst exhibited a much higher MAL selectivity than those of re-MgxAl–LDHs.

Synthesis, DFT Calculations, DNA Binding and Molecular Docking Studies on Biologically Active N-((3-(4-Methoxyphenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)naphthyl Derivatives

The biologically active pyrazole clubbed imino naphthyl derivatives have been designed and synthesized from 1-phenyl-3-methoxy phenyl-1H-pyrazol-4-carboxaldehyde and substituted naphthyl amines via acid catalyzed condensation reaction. All the synthesized compounds were well characterized by different spectroscopic and mass spectral techniques. The in vitro antibacterial, antifungal and antituberculosis studies were carried out. The molecular docking study was also done with the software Arguslab 4.0.1. The studied compounds showed moderate to good biological activities both experimentally and theoretically. Geometry optimization, DNA binding interaction and FMO analysis were also investigated with the help of Gaussian 16 package at B3LYP/6-31G(d,p) level.