Synthesis and characterization of levan hydrogels and their use for resveratrol release

Considering the need for systematic studies on levan based hydrogels to widen their use in drug delivery systems and biomedical applications, this study is mainly focused on the synthesis and comprehensive characterization as well as drug release properties of hydrogels based on Halomonas levan (HL) and its chemical derivatives. For this, hydrolyzed and phosphonated HL derivatives were chemically synthesized and then cross-linked with 1,4-Butanediol diglycidyl ether (BDDE) and the obtained hydrogels were characterized in terms of their swelling, adhesivity, and rheological properties. Both native and phosphonated HL hydrogels retained their rigid gel like structure with increasing shear stress levels and tack test analysis showed superior adhesive properties of the phosphonated HL hydrogels. Moreover, hydrogels were loaded with resveratrol and entrapment and release studies as well as cell culture studies with human keratinocytes were performed. Biocompatible and adhesive features of the hydrogels confirmed their suitability for tissue engineering and drug delivery applications.

A Review on Heteroaryl Substituted Pyrazolines with their Pharmacological Activity and SAR Studies

In step with the development of organic chemistry, heterocyclic compounds play an important part. Electron-rich nitrogen containing heterocyclic compounds and their derivatives play key role in diverse biological activities. The wide-ranging functionality and stereochemical complexity in a five-member ring structure is shown by the pyrazole nucleus, which has two nitrogen atoms and exhibit aromatic character. The medicinal chemists have been using the relationship between chemical structure and biological activity of a molecule in drug discovery as the driving force to guide synthetic efforts, to design new chemical derivatives. It has been reported that pyrazoline derivatives possess a broad spectrum of biological activities such as antibacterial, antimicrobial, anti-inflammatory, antioxidant, antidiabetic, anticancer, antifungal, antitubercular, antidepressant, anticonvulsant and analgesic activities. They also possess some potent receptor selective biological activities like monoamine oxidases (MAOs) inhibitor, Nitric oxide synthase (NOS) inhibitor, Angiotensin converting enzyme (ACE) inhibitor, cholecystokinin-1 receptor antagonist and estrogen receptor (ER) ligand activity. Hence in this article, we focus on the pyrazole derivatives having heteroaryl substituents and their pharmacological activities along with their structure–activity relationships in order to create opportunities to explore the full potential of these compounds. Keywords: Heterocyclic compounds, Pyrazolines, Claisen-Schmidt condensation, Chalcone.

PHARMACEUTICAL WORLD OF PERMEATION ENHANCERS

The drugs with poor solubility results in delayed absorption which consequently affects the bioavailability. There are many drugs which are having good therapeutic value but not used commercially because of this reason. The permeation enhancers are therefore being utilized to counter this problem. There are many such synthetic and natural materials which have the ability to enhance the drug permeation rate. The essential oils, alcohols, terpenes, azoles and many other chemical derivatives have the capability to be used for permeation enhancer. The present review work suggested the role of permeation enhancer in the pharmaceutical world.

Antiviral Activity of Isoquinolone Derivatives against Influenza Viruses and Their Cytotoxicity

Influenza viruses are one of the major causative agents for human respiratory infections. Currently, vaccines and antivirals approved for preventing and treating viral infections are available. However, limited protection efficacy and frequent emergence of drug-resistant viruses stand for a need for the development of antivirals with different chemical skeletons from existing drugs. Screening of a chemical library identified an isoquinolone compound (1) as a hit with 50% effective concentrations (EC50s) between 0.2 and 0.6 µM against the influenza A and B viruses. However, it exhibited severe cytotoxic effects with a 50% cytotoxic concentration (CC50) of 39.0 µM in canine kidney epithelial cells. To address this cytotoxic issue, we synthesized an additional 22 chemical derivatives. Through structure-activity, as well as structure-cytotoxicity relationship studies, we discovered compound 21 that has higher EC50 values ranging from 9.9 to 18.5 µM, but greatly alleviated cytotoxicity with a CC50 value over 300 µM. Mode-of-action and cell type-dependent antiviral experiments indicated that it targets viral polymerase activity and functions also in human cells. Here, we present a new class of viral polymerase inhibitors with a core skeleton of isoquinolone, of which antiviral activity could be better improved through following design and synthesis of its derivatives for drug development.

Synthetic Advances against Coronaviruses: A Short Review of the Recent Literature on Newly Synthetized Derivatives and Recently Developed Strategies

The coronavirus pandemic is a modern social emergency and the biggest global challenge since the Second World War. Since the pandemic began in China at the end of 2019, the disease spread to every landmass except Antarctica. The effect of antiviral drugs on the new corona virus has been tested, but no basic and complete cure has been found, although there are many drugs such as interleukin-6 inhibitor, monoclonal antibody and corticosteroid which remarkably reduced mortality of critically ill COVID-19 patients in a major clinical trial. Although not enough experimental data has been released yet, many researchers have hailed the result as a step in the right direction. In this review, a series of the newly chemical derivatives were synthesized and evaluated against human coronavirus. Many derivatives found to be active in inhibiting the cellular infection of human coronavirus which causes the SARS-CoV-2pandemic. This mini- review summarizes the synthesis of these new antiviral derivatives that target coronaviruses and describes general current strategies and models for developing antiviral drugs. The review aims to provide a starting point for medicinal chemists to synthesize necessary and effective drugs against coronaviruses.

EPCT-17. DEVELOPING EYA PHOSPHATASE INHIBITORS WITH ON-TARGET EFFECTS IN SHH-MEDULLOBLASTOMA

Medulloblastoma, one of the most frequent malignant pediatric brain tumors, encompasses four molecularly and clinically distinct cancers. Sonic hedgehog (SHH)-subtype medulloblastoma constitutes about 30% of medulloblastomas, and therapies targeting the SHH pathway can lead to new highly selective treatment. The haloacid dehalogenase (HAD) phosphatase Eyes Absent 1 (EYA1) is critically involved in the development and progression of SHH-medulloblastoma: Eya1 is highly expressed in SHH-medulloblastomas, and single cell sequencing indicates that Eya1 is a consistent feature that can be detected in every individual cancer cell. Inhibition of EYA1 interrupts SHH pathway signaling. During normal development, EYA1 promotes symmetric division of cerebellar granule cell precursors (GCPs), the cells of origin for SHH-subtype medulloblastoma, and reduced levels of EYA1 decrease medulloblastoma mortality rates in mouse models. Therefore, targeting EYA1 may be a novel therapeutic avenue for these pediatric cancers. Benzarone derivatives have been suggested as allosteric EYA-inhibitors, and benzarone provides a promising platform for chemical derivatives. Here, we develop 60 novel benzarone derivatives and assess their efficacy in inhibiting SHH-medulloblastoma growth through the inhibition of EYA1. Several of the new compounds inhibit EYA1 phosphotyrosine phosphatase activity in a cell-based assay, interrupt SHH pathway, and prevent SHH-medulloblastoma growth in vitro. Our results show that these novel benzarone derivatives are a new promising avenue for developing therapeutics for pediatric SHH-medulloblastoma via inhibition of EYA phosphatases.

Druggability of cavity pockets within SARS-CoV-2 spike glycoprotein and pharmacophore-based drug discovery

Aim: Virus spike glycoprotein of SARS-CoV-2 is a good target for drug discovery. Objective: To examine the potential for druggability of spike protein for pharmacophore-based drug discovery and to investigate the binding affinity of natural products with SARS-CoV-2 spike protein. Methods: Druggable cavities were searched though CavityPlus. A pharmacophore was built and used for hit identification. Autodock Vina was used to evaluate the hits' affinities. 10 chemical derivatives were also made from the chemical backbone to optimize the lead compound. Results: 10 druggable cavities were found within the glycoprotein spike. Only one cavity with the highest score at the binding site was selected for pharmacophore extraction. Hit identification resulted in the identification of 410 hits. Discussion: This study provides a druggable region within viral glycoprotein and a candidate compound to block viral entry.

Seaweed Polysaccharide Based Products and Materials: An Assessment on Their Production from a Sustainability Point of View

Among the various natural polymers, polysaccharides are one of the oldest biopolymers present on the Earth. They play a very crucial role in the survival of both animals and plants. Due to the presence of hydroxyl functional groups in most of the polysaccharides, it is easy to prepare their chemical derivatives. Several polysaccharide derivatives are widely used in a number of industrial applications. The polysaccharides such as cellulose, starch, chitosan, etc., have several applications but due to some distinguished characteristic properties, seaweed polysaccharides are preferred in a number of applications. This review covers published literature on the seaweed polysaccharides, their origin, and extraction from seaweeds, application, and chemical modification. Derivatization of the polysaccharides to impart new functionalities by chemical modification such as esterification, amidation, amination, C-N bond formation, sulphation, acetylation, phosphorylation, and graft copolymerization is discussed. The suitability of extraction of seaweed polysaccharides such as agar, carrageenan, and alginate using ionic solvent systems from a sustainability point of view and future prospects for efficient extraction and functionalization of seaweed polysaccharides is also included in this review article.