Chemical Biology Letters https://pubs.thesciencein.org/journal/index.php/cbl <p>Chemical Biology Letters is a peer reviewed journal for publication of research and review articles from Medicinal Chemistry, BioChemistry, Chemical Biology, Drug Development and Drug Delivery related studies.</p> en-US pubs@thesciencein.org (Editorial, Chem Biol Lett) pubs@thesciencein.org (Tech Support, ScienceIn) Fri, 10 Jun 2022 12:41:22 +0000 OJS 3.3.0.11 http://blogs.law.harvard.edu/tech/rss 60 Medicinal active applications of Dibenzofuran derivatives https://pubs.thesciencein.org/journal/index.php/cbl/article/view/374 <p>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.&nbsp; 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.</p> Mohammad Roshan Shoaib Savanur, Abhishek Kumar, Manoj Kumar, Sonu Kumar Copyright (c) 2022 ScienceIn Publishing https://pubs.thesciencein.org/journal/index.php/cbl/article/view/374 Sat, 02 Jul 2022 00:00:00 +0000 Lipid based self-assembled nanostructures for therapeutic delivery applications https://pubs.thesciencein.org/journal/index.php/cbl/article/view/368 <p>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.</p> Krishan Kumar, Niranjan Chatterjee, Santosh Kumar Misra Copyright (c) 2022 ScienceIn Publishing https://pubs.thesciencein.org/journal/index.php/cbl/article/view/368 Wed, 01 Jun 2022 00:00:00 +0000 Computational assisted designing, screening, and synthesis of novel Inhibitor of malarial aspartic proteases Plasmepsin I https://pubs.thesciencein.org/journal/index.php/cbl/article/view/364 <p>Aspartic protease enzymes of <em>Plasmodium falciparum</em> such as plasmepsin I (<em>Pf</em>Plm I) have been recognized as an interesting drug target for antimalarial drug discovery. For the immediate requirement of inhibitors of this enzyme, a computational approach was used to design HEA and piperazine analogs. We virtually screened 301 novel compounds based on validated pharmacophores <em>i.e.</em>, hydroxyethyl amine (HEA) and piperazine against <em>Pf</em>Plm I. The obtained hit compound in complex with <em>Pf</em>Plm I was subjected for molecular dynamics (MD) simulations at 200ns and found stable. Hit compound was further validated by wet lab experiments.</p> <p>&nbsp;<em>Keywords: Plasmepsin, Plasmodium, Proteases, Antimalarial drug, Analogs. </em></p> Amit Kumar Gautam, Rupini Boyina Copyright (c) 2022 ScienceIn Publishing https://pubs.thesciencein.org/journal/index.php/cbl/article/view/364 Wed, 22 Jun 2022 00:00:00 +0000 Impact of Ayurvedic drug Tinospora cordifolia in hyperlipidemia induced dysbiosis https://pubs.thesciencein.org/journal/index.php/cbl/article/view/363 <p>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. <em>Tinospora cordifolia</em> (Willd.) Miers ex Hook. F. &amp; 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 <em>Tinospora cordifolia</em> 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 14<sup>th</sup> 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 <em>Peptostreptococcs asaccharolyticus</em>, <em>Clostridium difficile</em>, <em>Faecalibacterium prausnitzii</em>, <em>Bifidobacterium</em>, <em>Subdoligranulum</em>, <em>Lactobacillus</em>, <em>Clostridium sporogenes</em>, <em>E</em>. <em>coli</em> 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 (&gt;2.0 fold, p&lt;0.005). However, TCE treatment reverted the levels of these metabolites and therefore, gut microflora. Also, <em>Cloacibacterium haliotis</em>, <em>Lactobacillus</em>, <em>Clostridium,</em> and <em>Bifidobacterium</em> population decreased in HPL patients. Increased secretion of yeast or <em>Candida albicans</em> associated metabolites was because of their increased population. Hence, TCE treatment enhanced the growth of useful gut microbiota in hyperlipidemia patients.</p> Aarti Yadav, Amey Shirolkar, Rajesh Dabur Copyright (c) 2022 ScienceIn Publishing https://pubs.thesciencein.org/journal/index.php/cbl/article/view/363 Sun, 24 Apr 2022 00:00:00 +0000 Establishment of in silico prediction methods for potential bitter molecules using the human T2R14 homology-model structure https://pubs.thesciencein.org/journal/index.php/cbl/article/view/351 <p>Bitterness is sensed by human taste receptors (hT2Rs) consisting of G protein-coupled receptors (GPCRs). The construction of an <em>in silico</em> evaluation system for bitter molecules using human T2R structure information will enable the identification of new bitter molecules and bitter blockers, which will contribute to food and drug development. Since the crystal structures of the hT2Rs have not been elucidated, we attempted to construct <em>in silico</em> discrimination methods for potential bitter molecules using the hT2R14 model structure in the GPCRdb that was constructed by the homology modelling method. Although the hT2R14 model structure was constructed using characteristics of existing bitter molecules, it was not previously clear whether it could be used for the prediction of new bitter molecules and bitter blockers. In this study, we established novel methods of predicting potential bitter molecule interactions with hT2R14 using datasets of compounds from ChemBridge and FEMA GRAS libraries. We used docking simulation tools, molecular dynamics simulation tools, structure-based machine learning (ML) tools, and sequence-based ML tools to establish potential bitter molecule prediction systems for hT2R14. Finally, we constructed novel <em>in silico</em> prediction systems, one of which can evaluate potential bitter molecules with high accuracy (AUC = 0.850) using consensus scoring based on the structure-based ML tools OnionNet, GNINA and BAPA.</p> Kohei Kuriki, Ryo Matsumoto, Chiori Ijichi, Junichi Taira, Shunsuke Aoki Copyright (c) 2022 ScienceIn Publishing https://pubs.thesciencein.org/journal/index.php/cbl/article/view/351 Mon, 16 May 2022 00:00:00 +0000 In Silico analysis of Ceruloplasmin alteration in Oral Squamous Cell Carcinoma https://pubs.thesciencein.org/journal/index.php/cbl/article/view/342 <p>Oral Squamous Cell Carcinoma (OSCC) incidence in India is very high, reaching 37.2 % of all cancer cases diagnosed in the advanced stages, extending a need to explore valuable diagnostic, therapeutic, and prognostic biomarkers for OSCC. Ceruloplasmin (CP), a multifunctional molecule involved in iron metabolism and copper transport, has been found to be upregulated in multiple tumor types, however its expression profile and prognostic potential, in OSCC remains unexplored. Using in silico analysis approach, we found Ceruloplasmin mRNA and protein expression greatly increased in high-grade oral cancer patients, suggesting ceruloplasmin could be a potential prognostic marker for late stage OSCC. On integration of gene expression profiles, molecular interaction network visualization suggested strong correlation between ceruloplasmin and redox metabolism, immune-related pathways, and cancer progression. We observed Ceruloplasmin expression to be correlated with negative regulators of T-cell immune response as well as shorter survival times. Our findings suggest that ceruloplasmin associated redox metabolism axis, iron homeostasis as well as immunoregulation can be targeted to develop a potential therapeutic approach for high grade OSCC patients.</p> Saniya Arfin, Neel Mani, Brijesh Rathi, Dhruv Kumar Copyright (c) 2022 ScienceIn Publishing https://pubs.thesciencein.org/journal/index.php/cbl/article/view/342 Mon, 16 May 2022 00:00:00 +0000 Genome-wide mutation/SNP analysis, biological characteristics, and Pan-India prevalence of SARS-CoV-2 Variants of Concern https://pubs.thesciencein.org/journal/index.php/cbl/article/view/331 <p>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<strong>,</strong> 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 <em>vis-à-vis</em> 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.</p> Nimita Kant, Shamashree Samanta, Ishika Panchal, Abhishek Pandey, Lagna Ghatak, Adyasha Rout, Jitendra Kumar Chaudhary Copyright (c) 2022 ScienceIn Publishing https://pubs.thesciencein.org/journal/index.php/cbl/article/view/331 Wed, 16 Feb 2022 00:00:00 +0000 Use of Tyrosine Kinase Inhibitors for treating Type 2 Diabetes Mellitus: An appraisal https://pubs.thesciencein.org/journal/index.php/cbl/article/view/320 <p>Tyrosine Kinase enzymes are known to play a significant role in tumor cell proliferation, stimulation of angiogenesis and metastasis and also show antiapoptotic effects. Therefore, Tyrosine Kinase inhibitors (TKIs) have been traditionally used to cure cancer. However, recently, there has been lot of interest in the possible use of TKIs for developing a new line of therapy for Type 2 Diabetes Mellitus (T2DM). Here, the authors have tried to summarize the seminal studies establishing the possible use of TKIs for T2DM. Authors conclude that there is lot of evidence suggesting the potential application of TKIs for treating T2DM, however, this hypothesis is still in its infancy stage. The animal models show promising results but there is an urgent need for detailed clinical investigations to establish this connection.</p> Kunika Saini, Smriti Sharma Copyright (c) 2022 ScienceIn Publishing https://pubs.thesciencein.org/journal/index.php/cbl/article/view/320 Tue, 22 Mar 2022 00:00:00 +0000 Synthetic strategies and medicinal applications of Quinoline-Pyrimidine hybrids https://pubs.thesciencein.org/journal/index.php/cbl/article/view/318 <p>The growing need to overcome the drug-resistance to bio-active molecules and the need for enhancement of properties in functional materials prompted the demand for new derivatives of existing moieties and development of more active new molecules. This effort culminated in the synthesis of a variety of molecules which often combined two active moieties into one single molecule such as the quinoline-pyrimidine hybrids. Quinoline-pyrimidine hybrids, though, include a wide class of molecules which vary based on the type of linkage combining the two moieties- quinoline and pyrimidine. This review focuses on these different classes of molecules, various developments in the synthesis of these hybrids and the biomedical applications of the synthesized molecules. Recently, greener methods like one-pot reactions and microwave assisted reactions have been utilized to synthesize some of the quinoline-pyrimidine hybrids and quite a few of the synthesized molecules have shown better or at par activity as the existing reference molecules.</p> Alitta Anna Cheriyan, Libi Thomas, Anchal Singhal Copyright (c) 2022 ScienceIn Publishing https://pubs.thesciencein.org/journal/index.php/cbl/article/view/318 Mon, 14 Mar 2022 00:00:00 +0000 Novel Inhibitors of malarial aspartyl proteases, plasmepsin II and IV: In silico design and validation studies https://pubs.thesciencein.org/journal/index.php/cbl/article/view/315 <div> <p class="05Abstracttext"><span lang="EN-US">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 (<em>Pf</em></span><span lang="EN-US">Plm II) and plasmepsin IV (</span><em><span lang="EN-US">Pf</span></em><span lang="EN-US">Plm 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.</span></p> </div> Prem Prakash Sharma, Aaftaab Sethi, Binit Dwivedi, Maria Grishina, Brijesh Rathi, Geeta Singh Copyright (c) 2022 ScienceIn Publishing https://pubs.thesciencein.org/journal/index.php/cbl/article/view/315 Sun, 02 Jan 2022 00:00:00 +0000 Higher plants exert interspecific effects on the phytoecdysteroids contents in Tinospora cordifolia https://pubs.thesciencein.org/journal/index.php/cbl/article/view/312 <p>Phytoecdysteroids are known for anabolic and adaptogenic properties. Hence, these are the point of interest in sports medicine and the pharmaceutical industry. Phytoecdysteroid occurrence varies in different plant parts, and also due to seasons and geographical locations. However, variations due to interspecific interactions of plants have not been explored to date. <em>Tinospora</em><em> cordifolia </em>has been reported to contain some phytoecdysteroids and is known to have anabolic and rejuvenating properties. Hence, the effect of interspecific interactions on phytoecdysteroid contents was explored in the current study using HPLC-QTOF-MS. Initial analysis of mass data based on characteristic fragment ions and loss of multiple water molecules validated the presence of 10 phytoecdysteroids and 4 derivatives across the samples screened. Principle component analysis (PCA) and partial least square discriminant analysis (PLS-DA) analysis showed significant (p&gt;0,05) variations in phytoecdysteroid patterns due to interspecific interactions. Statistical analysis revealed that&nbsp;<em>T. cordifolia </em>having interactions with &nbsp;<em>A</em>. <em>lebbeck</em>&nbsp;and&nbsp;<em>A</em>.&nbsp;<em>nilotica</em> formed separate distant groups, whereas. <em>T. cordifolia </em>having interactions with<em> A</em>.&nbsp;<em>indica</em>&nbsp;is the most distant group among other groups. <em>T. cordifolia</em> co-occurred with&nbsp;<em>A</em>.&nbsp;<em>indica</em>&nbsp;showed the highest number of up-regulated phytoecdysteroids, Fold change analysis showed that interspecific interactions of <em>T. cordifolia</em> with <em>A. indica</em> increased the contents of 3-dehydroecdysone (2-fold), makisterone A (4.8-fold), 24-methylshidasterone (4.3-fold), 1-hydroxy-20,22-didehydroxysterone (2-fold), 1-hydroxy-22-deoxy-20,21-dehydroecdysone (2-fold), cycleasterone A(3.3-fold), and 3β,5α,14α-trihydroxyergosta-7,22-diene-6-one (2.5-fold) in comparison to other plants. Hence, study indicate the interspecific interactions with&nbsp;<em>T. cordifolia</em>&nbsp;change the phytoecdysteroids pattern, hence its medicinal properties.</p> Aarti Yadav, Surender Yadav, Rajesh Dabur Copyright (c) 2022 ScienceIn Publishing https://pubs.thesciencein.org/journal/index.php/cbl/article/view/312 Tue, 01 Feb 2022 00:00:00 +0000 Source optimization, characterization, assessing biocompatibility and drug loading efficiency of biogenic silica particles from agro wastes https://pubs.thesciencein.org/journal/index.php/cbl/article/view/311 <p>Biogenic Silica Nanoparticles (BSN) were manufactured from different agro-wastes and their physico-chemical characterization and suitability as a drug carrier were tested. All the starting materials yielded high purity BSN, but the percentage of yield differed, with Indian goose grass and rice husk giving the highest percentage yield. Different conditions adopted in the manufacture were found to affect the amorphous nature of BSN produced. The BSN remained amorphous and porous at temperatures below 700°C. BSN at 500°C was found to have the best surface area and zeta potential which was found favorable in drug surface modifications and drug loading. BSN was not toxic to cells up to 200µg/mL and slightly improved the antioxidant response. Rice husk is a viable by-product of rice milling industry which can be used as a precursor for biogenic silica. Acid treatment followed by calcination at 500°C yielded high-quality BSN. Different physical characterization using SEM, TEM, BET, XRD, XRF etc revealed that the particles are spherical with 50-100 nm diameters and surface area 232m<sup>2</sup>/g. The prepared BSN were highly pure (&gt;99%). The cell viability study revealed the excellent biocompatibility of BSN. Propidium Iodide staining had shown that there were no significant changes in the nuclear morphology of the cells treated with BSN. Curcumin loaded BSN showed a slightly better ameliorating effect on the oxidative stress response caused by cypermethrin treatment than free curcumin alone. Surface modification of BSN with PEG and chitin was found to improve the antioxidant power of BSN and its drug loading efficiency. All these in vitro observations suggest the possibility of harnessing BSN isolated from rice husk as an effective drug carrier, or for other biomedical applications.</p> Aparna A Menon, Radhakrishna Gopala Pillai Copyright (c) 2022 ScienceIn Publishing https://pubs.thesciencein.org/journal/index.php/cbl/article/view/311 Sun, 09 Jan 2022 00:00:00 +0000 In silico study of phytochemicals for anticholinesterase activity as a potential drug target against Alzheimer's disease https://pubs.thesciencein.org/journal/index.php/cbl/article/view/310 <p>Alzheimer's disease (AD) is characterized by down-regulated levels of neurotransmitter acetylcholinesterase (AchE) and butyrylcholinesterase (BchE) in the neocortex and hippocampus; and aberrant processing and polymerization of Amyloid Precursor Protein (APP). Inhibition of cholinesterase (ChE) activity will effectively measure in AD treatment. In the present study, in silico analysis of anticholinesterase activity by 18 plant phytochemicals revealed four phytochemicals Quercetin, Cirsimaritin, Genkwanin and Genistein could be potential drugs candidates as they showed high binding affinity and interaction with the target protein AchE and BchE. These phytochemicals may play an essential role in regulating ChE activity in AD patients. Also, they are previously reported to play a vital role in altering other AD contributing factors. Thus, the present study reports potential drug targets that can be used to develop a drug against AD after experimental validation.</p> Tushar T Khandagale, Kuldeepkumar Singh, Sangeeta Sinha, Akshita Puri Copyright (c) 2022 ScienceIn Publishing https://pubs.thesciencein.org/journal/index.php/cbl/article/view/310 Tue, 22 Feb 2022 00:00:00 +0000 A comprehensive review on therapeutic properties of Mustard Oil and Olive Oil https://pubs.thesciencein.org/journal/index.php/cbl/article/view/309 <p>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 <em>in vitro</em> and <em>in vivo</em> studies. However, their use in clinical studies is very little known.</p> Tarisha Gupta, Ratandeep, Pooja, Laishram Saya Copyright (c) 2021 ScienceIn Publishing https://pubs.thesciencein.org/journal/index.php/cbl/article/view/309 Wed, 08 Dec 2021 00:00:00 +0000 Paraquat treatment modulated the stress erythropoiesis response in bone marrow and liver of the splenectomized mice https://pubs.thesciencein.org/journal/index.php/cbl/article/view/306 <p>Spleen serves as a secondary lymphoid and primary erythropoietic organ in neonates and in acute anemic conditions. Splenectomy is the process of surgical removal of spleen, which is used for the treatment of a number of anemic, leukemia and lymphoma patients. In the present investigation, we have analyzed the modulation of stress erythropoietic response in splenectomized condition. The splenectomized mice were treated with the repeated doses of paraquat (10 mg/kg intra-peritoneal on alternate days). Erythroid progenitor cells in bone marrow and liver were examined by staining with the anti-glycophorin (anti-Ter119) and transferrin (CD71) and monitoring the receptor expression. Paraquat treatment shows a moderate effect on the blood erythrocytes count, hemoglobin levels and reticulocytes percentages in blood circulation however induced the production of reactive oxygen species (ROS) in erythrocytes of splenectomized mice. The relative proportions and absolute recoveries of erythroid precursor cells in bone marrow were declined significantly at earlier time points post paraquat treatments. However, these cells begin to recover from day 14 and 21 and come to basal level on day 28. The proportion of erythroid cells in liver was slightly decreased on day 7 but it increased significantly on day 14. Interestingly, the proliferative activity of erythroid cells in the bone marrow increases, probably to compensate the loss of erythrocytes in circulation</p> Nitin Bhardwaj, Ashutosh Singh, Harish Chandra, Kartikey Kumar Gupta Copyright (c) 2022 ScienceIn Publishing https://pubs.thesciencein.org/journal/index.php/cbl/article/view/306 Sat, 26 Feb 2022 00:00:00 +0000