Gelatin-based carbon quantum dot-molecularly imprinted polymer: Safe photoluminescent core-shell nano-carrier for the pH-responsive anticancer drug delivery.

This study aims to synthesize a core-shell gelatin-based carbon quantum dot-molecularly imprinted polymer (MIP@g-CQD) via the precipitation free-radical polymerization process using methotrexate (MTX) as a model anticancer template. To investigate the efficiency of the prepared photoluminescent MIP@g-CQD as a pH-responsive nano-carrier, MTX was loaded into MIP@g-CQD by soaking in a drug solution and the release behavior of the loaded drug was evaluated in the necessary pH values (7.4, 5). The successful synthesis of materials was characterized using PL, TEM, FE-SEM, DLS, and FT-IR analyses. Interestingly, the created cavities in the core-shell nano-carriers can interact with the MTX molecules effectively, leading to an increase in the loading capacity. According to the obtained results from Langmuir adsorption isotherms, the imprinting factor was calculated (IF = 4.91). Also, the binding kinetics of MTX revealed the creation of particular recognition sites in the core-shell polymeric network. The MTX-loaded MIP@g-CQD displayed a low rate and limited release at the simulated physiological environment (pH 7.4, 37 °C), but it is increased at tumor tissue (pH 5, 41 °C) conditions, which can lead to long-term and sustained release of MTX in the desired target. This property of MIP@g-CQD could avoid the release of MTX in normal physiological conditions, decreasing the possible side effects of MTX drug. Owing to the existence of amide functional groups in the nano-carrier structure and its negatively charged nature, the MTT assay displayed desirable cytotoxicity against the breast cancer cell line (MCF-7) for the MTX-loaded nano-carrier. According to the obtained results, the prepared safe photoluminescent MIP@g-CQD with appropriate pH-responsivity has a high ability to be applied as an anticancer and bio-detection agent.

Isocyanide-based multicomponent reactions for the synthesis of benzopyran derivatives with biological scaffolds.

Benzopyrans (BZPs) are among the most privileged and influential small O-heterocycles that form the core of many natural compounds, commercial drugs, biological compositions, agrochemicals, and functional materials. BZPs are divided into six general categories including coumarins, chromans, 2H-chromenes, 4H-chromenes, chromones, and 4-chromanones, each of which is abundant in many plants and foods. These oxygenated heterocyclic compounds are fascinating motifs and have extensive applications in biology and materials science. Hence, numerous efforts have been made to develop innovative approaches for their extraction and synthesis. However, most of them are step-by-step or multi-step strategies that suffer from waste material generation and a tedious extraction process. Isocyanide-based multicomponent reactions (I-MCRs) offer a highly efficient method for overcoming these problems. The I-MCR is a simple and environmentally friendly one-pot domino procedure that does not require intermediate isolation or workup and is generally more efficient in material usage. This review covers all research articles related to I-MCRs for synthesizing BZP derivatives from the beginning to the middle of the year 2023. This strategy will be useful for organic and pharmaceutical chemists to design new drugs and optimize the synthesis steps of biological compounds and commercial drugs with benzopyran cores.

Multicomponent reactions as a potent tool for the synthesis of benzodiazepines.

Benzodiazepines (BZDs), a diverse class of benzofused seven-membered N-heterocycles, display essential pharmacological properties and play vital roles in some biochemical processes. They have mainly been prescribed as potential therapeutic agents, which interestingly represent various biological activities such as anticancer, anxiolytic, antipsychotic, anticonvulsant, antituberculosis, muscle relaxant, and antimicrobial activities. The extensive biological activities of BZDs in various fields have encouraged medicinal chemists to discover and design novel BZD-based scaffolds as potential therapeutic candidates with the favorite biological activity through an efficient protocol. Although certainly valuable and important, conventional synthetic routes to these bicyclic benzene compounds contain methodologies often requiring multistep procedures, which suffer from waste materials generation and lack of sustainability. By contrast, multicomponent reactions (MCRs) have recently advanced as a green synthetic strategy for synthesizing BZDs with the desired scope. In this regard, MCRs, especially Ugi and Ugi-type reactions, efficiently and conveniently supply various complex synthons, which can easily be converted to the BZDs via suitable post-transformations. Also, MCRs, especially Mannich-type reactions, provide speedy and economic approaches for the one-pot and one-step synthesis of BZDs. As a result, various functionalized-BZDs have been achieved by developing mild, efficient, and high-yielding MCR protocols. This review covers all aspects of the synthesis of BZDs with a particular focus on the MCRs as well as the mechanism chemistry of synthetic protocols. The present manuscript opens a new avenue for organic, medicinal, and industrial chemists to design safe, environmentally benign, and economical methods for the synthesis of new and known BZDs.

Isocyanide-based consecutive Bargellini/Ugi reactions: an efficient method for the synthesis of pseudo-peptides containing three amide bonds.

Isocyanide-based consecutive Bargellini/Ugi multicomponent reactions as a combinatorial strategy have been developed for the synthesis of new class of pseudo-peptides. Via Bargellini reaction 3-carboxamido-isobutyric acids are prepared using acetone, chloroform, sodium hydroxide, and isocyanides. Then, using Ugi multicomponent reaction strategy, pseudo-peptides containing three amide bonds are synthesized using the Bargellini reaction product, aldehydes, amines, and isocyanides. This is an efficient and eco-friendly approach for easy access to wide variety of structurally diverse, drug-like pseudo-peptides from cheap and readily available precursors in high yields.

Cyclic Imines in Ugi and Ugi-Type Reactions.

Ugi four-component reactions (U-4CRs) are widely recognized as being highly efficient for the synthesis of pseudopeptides. However, the products of these reactions are not so interesting as drug candidates because they are not conformationally restricted enough for a potent interaction with biological targets. One possible way to overcome this problem is to replace amine and oxo components in the U-4CRs with cyclic imines in so-called Joullié-Ugi three-component reactions (JU-3CRs). This approach provides a robust single-step route to peptide moieties connected to N-heterocyclic motifs that are found as core skeletons in many natural products and pharmaceutical compounds. JU-3CRs also provide much better diastereoselectivity than their four-component analogues. We survey here the redesign of many synthetic routes for the efficient preparation of a wide variety of three-, five-, six-, and seven-membered heterocyclic compounds connected to the peptide backbone. Additionally, in the Ugi reactions based on the cyclic imines, α-acidic isocyanides, or azides can be replaced with normal isocyanides or acids, respectively, leading to the synthesis of N-heterocycles attached to oxazoles or tetrazoles, which are of great pharmaceutical significance. This Review includes all research articles related to Ugi reactions based on the cyclic imines to the year 2020 and will be useful to chemists in designing novel synthetic routes for the synthesis of individual and combinatorial libraries of natural products and drug-like compounds.

Doxorubicin Imprinted Photoluminescent Polymer as a pH-Responsive Nanocarrier.

In this work, an innovative doxorubicin (DOX) imprinted photoluminescent polymer via the precipitation free-radical polymerization strategy was developed based on graphene quantum dots as a pH-responsive nanocarrier. The prepared materials were characterized by Fourier transform infrared, scanning electron microscopy, photoluminescence, and dynamic light scattering techniques. Binding kinetics of DOX established specific recognition binding sites in the photoluminescent nanoscale molecularly imprinted polymer (PLMIP) structure. In vitro drug release behaviors exhibited a pH-controlled release in a sustained manner for the prepared photoluminescent nanocarriers. Due to the presence of pseudopeptide skeletons in the nanocarrier and a positively charged structure, the cytotoxicity study indicated that a DOX-loaded nanocarrier against human lung adenocarcinoma A549 cell lines has notable cytotoxicity. According to the obtained results, the prepared pH-responsive PLMIP has the potential to be employed as an anticancer and biodetection platform.

Encapsulation of graphene quantum dot-crosslinked chitosan by carboxymethylcellulose hydrogel beads as a pH-responsive bio-nanocomposite for the oral delivery agent.

Oral delivery most commonly used due to the non-invasive nature and the fact that avoids patient pain and discomfort in compression with the intravenous administration. Herein, the obtained graphene quantum dots (GQDs) from citric acid were employed as a cross-linker for chitosan (CS). Sodium salicylate (SS) as a model drug was loaded in the prepared graphene quantum dots-crosslinked chitosan hybrid bio-nanocomposite beads (CS-GQD). SS-loaded CS-GQD (CS-GQD/SS) was protected with pH-sensitive biopolymeric carboxymethylcellulose (CMC) hydrogel beads. The CMC encapsulated CS-GQD/SS bio-nanocomposite hydrogel beads (CS-GQD/SS@CMC) were characterized using FT-IR, PL and SEM analysis. For determination of surficial charge of the carrier, pH point of zero charges (pHpzc) was measured. In-vitro drug delivery tests were carried out in simulating the gastrointestinal tract conditions for proving the efficiency of the prepared beads as a controlled oral drug delivery. The synergistic effects of CMC and CS enhanced the stability of drug dosing for a long time with controlling the drug releases in the gastrointestinal tract conditions. The MTT test confirmed that the bio-nanocomposite beads have low toxicity against human colon adenocarcinoma HT29 cells. The obtained results showed that the prepared novel CS-GQD/SS@CMC could potentially be used as a safe carrier for oral drug delivery.

A novel bioelectrochemical sensing platform based on covalently attachment of cobalt phthalocyanine to graphene oxide.

Graphene oxide-cobalt phthalocyanine (GO-PcCo) hybrid material as a new electrocatalyst was synthesized and used successfully to fabrication of new biosensor for the electrooxidation of l-cysteine (CSH) in aqueous media. Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), and transmission electron microscopy (TEM) images revealed that cobalt phthalocyanine is covalently attachment on graphene oxide sheets as single layers GO-PcCo. Cyclic voltammetric studies showed that the GO-PcCo/glassy carbon electrode (GO-PcCo/GCE) improves electrochemical behavior of CSH oxidation, as compared to the GO and PcCo. In addition, the results indicated that GO and PcCo have a synergic effect in the electrooxidation of CSH. The catalytic oxidation responses were studied and the reaction mechanisms were discussed. The electrocatalytic behavior is further developed as a new detection scheme for CSH by chronoamperometry method and under optimized conditions, excellent analytical features, including high sensitivity and selectivity, low detection limit and satisfactory dynamic range, were achieved.