Design, synthesis and molecular docking studies of new Quinoxaline-linked-1,2,4-triazole-Sulfonamide hybrids as Anti-proliferative agents

Design, synthesis and molecular docking studies of new Quinoxaline-linked-1,2,4-triazole-Sulfonamide hybrids as Anti-proliferative agents

A new series of quinoxaline linked 1,2,4-triazole sulfonamide  derivatives were designed and efficiently synthesized. All compounds were characterized by their IR, 1HNMR, 13CNMR, and Mass spectral data, and elemental analysis. The final compounds (5a-m) were screened for in vitro anti-proliferative activity against cancer cell lines HeLa (lung), A549 (carcinoma), MCF-7 (breast) and HCT116 (colon).The  results revealed that the compounds 5k, 5l and 5d have shown promising activity as compared to etoposide. Predominantly, the compound 5k displayed greater activity on HeLa, A549, MCF-7and HCT116 with IC50 values of 1.97±0.09, 1.84±0.07, 3.10±0.04and 4.10±0.07 than the standard drug etoposide. Moreover, molecular docking studies of 5k, 5l and 5d on EGFR receptor suggested that the most potent compound 5k strongly binds to protein EGFR (pdbid: 4HJO). Furthermore, the compounds 5k and 5l displayed promising inhibitory activity over tyrosine kinase EGFR when compared with the standard erlotinib.

Design, synthesis and molecular docking studies of new Quinoxaline-linked-1,2,4-triazole-Sulfonamide hybrids as Anti-proliferative agents – https://pubs.thesciencein.org/journal/index.php/cbl/article/view/396

Chemical Biology Letters

Medicinal active applications of Dibenzofuran derivatives

Dibenzofuran is an important heterocyclic compound and is an important part of various natural compounds. There are various medicinal compounds containing dibenzofurans, sold in the market to combat different human diseases and plant infections. Research on dibenzofuran is an advancing field in the medicinal science. Several compounds are under the clinical trials and are expected to be utilized in various treatments. This review article encompasses various advancements in the study of these dibenzo derivatives. The biological activity of these scaffolds hovering around cytotoxicity of the cells, bacterial infections, fungal infections, type-2 diabetes, platelet coagulation and in the effective skin treatment, has been discussed in the following article.  The toxicology of the compound is also argued and selected biological applications are hereby discussed to make easier for the researchers to have a consolidated sight over the topic.

Investigation of molecular interaction between β-amyloid and insulin receptor: An in-silico study

The growth of amyloid β peptides arises from inappropriate cleavage of amyloid precursor protein that induces the formation of amyloid plaques in the brain. An excessive accumulation of amyloid β plaques promotes the development of dementia, specifically Alzheimer’s disease (AD). Histopathological evidence suggested that insulin resistance and type 2 diabetes condition have a stronger correlation with Alzheimer’s disease development. An increasing concentration of amyloid β leads to impaired binding of insulin to its receptor. Previous studies suggested that the monomeric form of amyloid β was the potential molecule, which can compete with insulin for receptor binding. The objective of this work was to study the molecular interactions of insulin and amyloid β to insulin receptors using protein-protein docking and molecular dynamics Simulations. Analysis of docked complexes suggested that there are common insulin receptor residues for insulin and amyloid β binding. Further molecular dynamics Simulations study reveals that the monomeric form of amyloid β interacts with a similar set of receptor residues as observed in the insulin-insulin receptor complex.

Lipid based self-assembled nanostructures for therapeutic delivery applications

The evolution of lipid nanoparticles (LNPs) has been remarkably interesting and in beneficent directions for food and health industries working towards human well being. Since the discovery of the first-generation lipid based self-assembled nanostructures, i.e., liposomes in the 1960s, it has witnessed significant advances in their development and distinctive potential in different application domains. Based on the composition and structure, these lipid based structures have varied from liposome to lipid nanoparticles such as nanostructured lipid carriers (NLCs) and solid lipid nanoparticles (SLN) to overcome certain limitation pertaining to their use in different fields. The outstanding application of LNPs as therapeutic delivery systems has made them key players to treat different human disorders including the fatal cancers. Their life-saving global contribution has recently been witnessed in the form of mRNA vaccines against deadly COVID-19. They have also significantly served purpose in other domains such as biomedical imaging, cosmetics, nutrition, and agriculture. Their prominent role is in the area of anticancer therapy as delivery vectors for nucleic acids and drugs. Some issues with respect to the cellular delivery of drugs and genes, such as circulation time and stability have been somewhat resolved, but the unmet goal of site-specific substantial delivery remains the main focus in LNPs development research. Despite the promise shown by LNPs in animal studies and the fact that technological advances in LNPs research have made the approval possible of a few formulations, therapeutic outcomes in human are not satisfactory. The LNPs technology has managed to survive due to possible tailoring of their properties by virtue of the possibility of altering the composition and modifying the surface. Therefore, enormous scientific endeavours are on the rise to transform lipid structures, composition along with tinkering with surface of LNPs. The alternative methods to guide LNPs coupled with advances in small molecule nucleic acid therapeutics and drug development technology to make the entry possible to specific cells may be effective in cancer therapy. The development is very promising; however enduring efforts are required till the goal is reached.

Impact of Ayurvedic drug Tinospora cordifolia in hyperlipidemia induced dysbiosis

Gut microbiota broadly impacts human health, but urinary microbial metabolites remain largely undefined. The concentration of microbial metabolites can be directly correlated with microbial populations in the human gut to define disease states. Tinospora cordifolia (Willd.) Miers ex Hook. F. & Thoms is being used for ages in the Indian ayurvedic system of medicine and it has hypolipidemic and hypoglycaemic activity. Present study investigate the MS-based metabolomics variations of possible gut microbiota associated metabolites in hyperlipidemia (HPL) and HPL treated with Tinospora cordifolia extract (TCE) (TRT). Twenty-four HPL male patients and 10 age-matched controls (HLT) were enrolled. Early morning fasting blood and urine samples were collected on days 0 and 14th of TCE treatment and subjected to lipid profiling and Q-TOF-MS analysis. Multivariate analysis showed urinary levels of urocanic acid, hydroxyphenylacetate, linolenic acid, phenylpropionate, hypoxanthine, and indole acetate produced by Peptostreptococcs asaccharolyticus, Clostridium difficile, Faecalibacterium prausnitzii, Bifidobacterium, Subdoligranulum, Lactobacillus, Clostridium sporogenes, E. coli were depleted in HPL patients as compared to healthy controls. In contrast, levels of serotonin, acetylleucine, hippuric acid, and arabinitol were found to be increased (>2.0 fold, p<0.005). However, TCE treatment reverted the levels of these metabolites and therefore, gut microflora. Also, Cloacibacterium haliotis, Lactobacillus, Clostridium, and Bifidobacterium population decreased in HPL patients. Increased secretion of yeast or Candida albicans associated metabolites was because of their increased population. Hence, TCE treatment enhanced the growth of useful gut microbiota in hyperlipidemia patients.

Genome-wide mutation/SNP analysis, biological characteristics, and Pan-India prevalence of SARS-CoV-2 Variants of Concern

The origin of COVID-19 pandemic, caused by SARS-CoV-2, was traced to Wuhan, China. Thereafter, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolved into various variants owing to genome-wide mutations, causing emergence of multiple variants, including Variant of Interest and Variant of Concern. Here, we discuss genomic architecture of SARS-CoV-2, as well as its multiple variants- alpha, beta, gamma, and delta, along with their biological properties, such as transmissibility, reduction in antibody-mediated neutralization, virulence, disease severity, vaccine effectiveness, and the prevalence across the India vis-à-vis world. Our data on VOC, pooled from the Global Initiative on Sharing All Influenza Data up to 31 October 2021, shows around 89% prevalence of delta VOC across various Indian States. Whereas alpha, beta, and gamma variants show 10.44%, 0.57%, and 0.11% prevalence, respectively. Compared with global scale, the reported Indian prevalence of alpha, beta, gamma, and delta are 0.40%, 0.63%, 0.04%, and 1.7%, respectively. Furthermore, prevalent vaccines of various natures show significantly reduced effectiveness against these VOCs, necessitating urgent need for development of effective prophylactic vaccines and potential therapy to contain the pandemic.

Novel Inhibitors of malarial aspartyl proteases, plasmepsin II and IV: In silico design and validation studies

In the dire need of novel inhibitors of enzymes, computational approaches have significantly expedited the drug discovery process. Aspartic protease enzymes of Plasmodium falciparum such as plasmepsin II (PfPlm II) and plasmepsin IV (PfPlm IV) have been recognized as an attractive drug target for antimalarial drug discovery. In line with this, we performed high-throughput screening of 316 novel compounds based on validated pharmacophore i.e., hydroxyethylamine (HEA) and piperazine against both PfPlm II and PfPlm IV. The obtained hit compound-protein complexes were subjected for molecular dynamics (MD) simulations at 200ns and found stable. Thermodynamic energy calculated for the complexes also supported compound’s stability within the binding pocket of plasmepsins. The results of our study strongly support an immediate validation of the virtually screened hits in biological systems.

A comprehensive review on therapeutic properties of Mustard Oil and Olive Oil

Plants and their extracts have been extensively studied for their efficacy in therapeutic applications. Their Essential Oils (EOs) are responsible for the majority of biological properties such as anticancer, antibacterial and antimicrobial, antioxidant, anti-inflammatory, and cardio-protective. The utilization of natural compounds is gaining a lot of attention these days. These oils act as natural alternatives to the modern medical system to cure the illness that occurs in the biological system. This review provides an overview of the impact of the two most important plant-based oils: Mustard oil and Olive oil, the role of their components in different biological activities leading to their therapeutic applications. Their intake provides health benefits by controlling the symptoms of the diseases that involve cancer, bacterial infections, inflammation, cardiovascular, and some other common diseases. Most of the results come from in vitro and in vivo studies. However, their use in clinical studies is very little known.

Journal of Molecular Chemistry

The Journal of Molecular Chemistry is a peer reviewed international journal at the heart of chemistry, meant to cover research at all stages from molecule design, synthesis to applications. The journal publishes research in chemistry at molecular level to applications in biological or physical/materials field. It covers the Organic Chemistry, synthetic organic chemistry, catalysis, new methodologies, natural product synthesis, new reaction pathways, peptide synthesis, small molecule synthesis, Chemistry research, chemical technology and other allied areas covering advances in chemistry and exploration of molecular applications in biology, medicine, polymer, materials and environment.

Journal of Molecular Chemistry

https://pubs.thesciencein.org/journal/index.php/jmc

The journal publishes full length research articles, review article, tutorial articles, expert opinions from all field of organic chemistry and allied chemistry research including Synthetic Organic Chemistry, Catalysis, Medicinal Chemistry, Materials Chemistry, Heterocyclic Chemistry, Macrocyclic chemistry, Polymer Chemistry, NanoChemistry, Chemical Engineering and all other research advances related to new chemistry development. The chemistry research fraternity is invited to submit their next excellent article on journal site

https://pubs.thesciencein.org/journal/index.php/jmc

Author guidelines and article templates are provided on the journal site.

Molecular Chemistry Letters

The Molecular Chemistry Letters is an international journal meant to provide a rapid forum for publication of quality original research from molecule design, synthesis and applications with major coverage in organic chemistry and interdisciplinary chemistry research. The Molecular Chemistry Letters covers the synthetic organic chemistry, catalysis, new methodologies, natural product synthesis, new reaction pathways, peptide synthesis, small molecule synthesis, Polymer chemistry, Medicinal Chemistry, Materials Chemistry, Chemistry Biology Interface research, chemical technology, green chemistry, environmental chemistry and other allied areas covering advances in chemistry.

Molecular Chemistry Letters

https://pubs.thesciencein.org/journal/index.php/mcl

The journal publishes short communications (letters), research articles, review article, tutorial articles, expert opinions from all field of organic chemistry and allied chemistry research including Synthetic Organic Chemistry, Catalysis, Heterocyclic Chemistry, Macrocyclic chemistry, Polymer Chemistry, NanoChemistry, Chemical Engineering and all other research advances related to new chemistry development. The chemistry research fraternity is invited to submit their next excellent article on journal site

https://pubs.thesciencein.org/journal/index.php/mcl

Author guidelines and article templates are provided on the journal site.