Chemical Biology Letters 2022-08-22T06:33:48+00:00 Editorial, Chem Biol Lett Open Journal Systems <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> Design and synthesis of new Nilutamide-1,2,3-triazole derivatives as in vitro Anticancer agents 2022-08-22T06:33:48+00:00 Malla Reddy Nallapu Rajender Vadluri Jeyanthi Arasan <p>The synthesis of novel 1,2,3-triazoles of Nilutamide (4a–4n) <em>via</em> Cu(I)-promoted 1,3-dipolar cycloaddition reaction between several terminal alkynes and 1-(3-azidopropyl)-5,5-dimethyl-3-(4-nitro-3-(trifluoromethyl)phenyl)imidazolidine-2,4-dione have been reported herein. <em>In vitro</em> anticancer activity studies of these synthesized compounds over two human prostate cell lines PC3 and DU-145 revealed that the compounds 4c, 4f and 4n exhibit slightly greater activity against two cell lines than the standard etoposide. Predominantly, the compound 4f displayed excellent activity over PC3 and DU-145 having IC<sub>50</sub> values of 1.84and 1.34 μM respectively. The three most potent compounds 4c, 4f and 4n were also investigated for their inhibitory potential against tyrosine kinase EGFR and found that compound 4f showed superior activity than the standard <em>erlotinib</em>, while remaining two compounds 4c and 4n showed comparable activity with the standard.</p> <p><em>URN:NBN:sciencein.cbl.2022.v9.405</em></p> 2022-09-14T00:00:00+00:00 Copyright (c) 2022 ScienceIn Publishing Design, synthesis and molecular docking studies of new Quinoxaline-linked-1,2,4-triazole-Sulfonamide hybrids as Anti-proliferative agents 2022-07-27T14:42:42+00:00 Malla Reddy Nallapu Rajender Vadluri Jeyanthi Arasan <p>A new series of quinoxaline linked 1,2,4-triazole sulfonamide&nbsp; derivatives were designed and efficiently synthesized. All compounds were characterized by their IR, <sup>1</sup>HNMR, <sup>13</sup>CNMR, and Mass spectral data, and elemental analysis. The final compounds (<strong>5a-m) </strong>were screened for <em>in vitro </em>anti-proliferative activity against cancer cell lines HeLa (lung), A549 (carcinoma), MCF-7 (breast) and HCT116 (colon).The&nbsp; results revealed that the compounds <strong>5k, 5l </strong>and <strong>5d </strong>have shown promising activity as compared to etoposide. Predominantly, the compound <strong>5k</strong> displayed greater activity on HeLa, A549, MCF-7and HCT116 with IC<sub>50</sub> 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 <strong>5k, 5l</strong> and <strong>5d</strong> on EGFR receptor suggested that the most potent compound <strong>5k </strong>strongly binds to protein EGFR (pdbid: 4HJO). Furthermore, the compounds <strong>5k</strong> and <strong>5l</strong> displayed promising inhibitory activity over tyrosine kinase EGFR when compared with the standard erlotinib.</p> 2022-07-25T00:00:00+00:00 Copyright (c) 2022 ScienceIn Publishing Medicinal active applications of Dibenzofuran derivatives 2022-06-30T15:36:11+00:00 Mohammad Roshan Shoaib Savanur Abhishek Kumar Manoj Kumar Sonu Kumar <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> 2022-07-02T00:00:00+00:00 Copyright (c) 2022 ScienceIn Publishing Investigation of molecular interaction between β-amyloid and insulin receptor: An in-silico study 2022-06-27T06:18:15+00:00 Rakesh Kumar Niharika Krishna Kumar Ojha Harlokesh Narayan Yadav Nanaocha Sharma Vijay Kumar Singh <p>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.</p> 2022-06-29T00:00:00+00:00 Copyright (c) 2022 ScienceIn Publishing Azabicyclononane derivative downregulates the P38 MAP-kinase pathway in colon cancer through apoptosis 2022-07-01T05:54:33+00:00 Bhavapriya Rajendran Venkatraman Manickam Ramasamy Tamizhselvi J Febin PrabhuDass Sathiyanarayanan Kulathu Iyer Krishnaraj Thirugnanasambantham Hairul-Islam Mohamed Ibrahim <p>Synthesized novel azabicyclononane derivatives have been extensively analyzed for its cytotoxic, anti-cancerous activities against various cancer types. We have synthesized a set of azabicyclononane derivatives and evaluated their activity in cancer. Among the three compounds checked, ABN-5d has an IC<sub>50</sub> value of 12.5 μM. <em>In vitro</em> cytotoxicity studies proved that, in addition to a significant IC<sub>50</sub> value of ABN-5d at 25µM against cancer cell lines (HCT116), Additionally the compound also demonstrated proliferative effects in enhancing the growth of non-cancerous cells (L929). This suggested the non-toxic nature of the compound and its selectivity toward cancer cells. Apoptosis assays (Annexin V/PI, cell cycle analysis, DNA fragmentation by DPA method, DNA laddering analysis, AO/EB dual staining, and DAPI staining, Morphological analysis using SEM) confirmed that ABN-5d is inducing apoptosis in the studied cancer cells. Expression analysis of 6 genes encoding demonstrated that ABN-5d is upregulating p53 expression significantly P&lt;0.001. Protein-ligand docking studies and western blot analysis confirmed that ABN-5d inhibits P38α MAP-kinase (binding energy -9.29Kcal/mol) and eventually downregulates the pathway. This study confirms ABN-5d as an effective anticancer agent which targets the MAPK pathway.</p> 2022-07-31T00:00:00+00:00 Copyright (c) 2022 ScienceIn Publishing Lipid based self-assembled nanostructures for therapeutic delivery applications 2022-06-08T04:14:44+00:00 Krishan Kumar Niranjan Chatterjee Santosh Kumar Misra <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> 2022-06-01T00:00:00+00:00 Copyright (c) 2022 ScienceIn Publishing Computational assisted designing, screening, and synthesis of novel Inhibitor of malarial aspartic proteases Plasmepsin I 2022-05-07T08:26:23+00:00 Amit Kumar Gautam Rupini Boyina <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> 2022-06-22T00:00:00+00:00 Copyright (c) 2022 ScienceIn Publishing Impact of Ayurvedic drug Tinospora cordifolia in hyperlipidemia induced dysbiosis 2022-04-28T13:45:13+00:00 Aarti Yadav Amey Shirolkar Rajesh Dabur <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> 2022-04-24T00:00:00+00:00 Copyright (c) 2022 ScienceIn Publishing Establishment of in silico prediction methods for potential bitter molecules using the human T2R14 homology-model structure 2022-05-11T09:51:32+00:00 Kohei Kuriki Ryo Matsumoto Chiori Ijichi Junichi Taira Shunsuke Aoki <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> 2022-05-16T00:00:00+00:00 Copyright (c) 2022 ScienceIn Publishing In Silico analysis of Ceruloplasmin alteration in Oral Squamous Cell Carcinoma 2022-03-22T05:39:45+00:00 Saniya Arfin Neel Mani Brijesh Rathi Dhruv Kumar <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> 2022-05-16T00:00:00+00:00 Copyright (c) 2022 ScienceIn Publishing Genome-wide mutation/SNP analysis, biological characteristics, and Pan-India prevalence of SARS-CoV-2 Variants of Concern 2022-02-21T00:22:04+00:00 Nimita Kant Shamashree Samanta Ishika Panchal Abhishek Pandey Lagna Ghatak Adyasha Rout Jitendra Kumar Chaudhary <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> 2022-02-16T00:00:00+00:00 Copyright (c) 2022 ScienceIn Publishing Use of Tyrosine Kinase Inhibitors for treating Type 2 Diabetes Mellitus: An appraisal 2022-01-22T05:38:33+00:00 Kunika Saini Smriti Sharma <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> 2022-03-22T00:00:00+00:00 Copyright (c) 2022 ScienceIn Publishing Synthetic strategies and medicinal applications of Quinoline-Pyrimidine hybrids 2022-01-17T03:29:51+00:00 Alitta Anna Cheriyan Libi Thomas Anchal Singhal <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> 2022-03-14T00:00:00+00:00 Copyright (c) 2022 ScienceIn Publishing Novel Inhibitors of malarial aspartyl proteases, plasmepsin II and IV: In silico design and validation studies 2022-01-02T04:35:50+00:00 Prem Prakash Sharma Aaftaab Sethi Binit Dwivedi Maria Grishina Brijesh Rathi Geeta Singh <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> 2022-01-02T00:00:00+00:00 Copyright (c) 2022 ScienceIn Publishing Higher plants exert interspecific effects on the phytoecdysteroids contents in Tinospora cordifolia 2021-12-24T08:50:21+00:00 Aarti Yadav Surender Yadav Rajesh Dabur <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> 2022-02-01T00:00:00+00:00 Copyright (c) 2022 ScienceIn Publishing