Chemical Biology Letters <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 (Editorial, Chem Biol Lett) (Tech Support, ScienceIn) Fri, 10 Jun 2022 12:41:22 +0000 OJS 60 Global Cancer Statistics 2022: the trends projection analysis <p class="05Abstracttext"><span lang="EN-US">Cancer is one of the most fatal diseases of recent times that causes several deaths every year. The disease variations in different parts of the world, the impact of available medical facilities, and other socio-economic factors have impacted the proper management of this disease. The comparative statistical data of cancer types like breast, prostate, colon, lung, lymph, blood, brain, and kidney cancers can be used to design treatment strategies and therapeutics development. With the advancement of science, several drugs besides diagnostic methods have emerged to control respective cancer and have assisted in curing this disease to some extent. The comparative statistics analysis for cancer about current prevalence is included here to bring a clear framework for the efforts towards future drug development to manage this disease. The availability of new diagnostics and therapeutics and advanced medical facilities in clinics impact cancer statistics. An evaluation of current trends and statistics of cancer pathology vis-à-vis theranostics (diagnostics as well as therapeutics) progress with possible application in clinical settings constitutes the core part of the discussion in this review.</span></p> <p class="05Abstracttext"><span lang="EN-US"><em>URN:NBN:sciencein.cbl.2023.v10.451</em></span></p> Bhupender S. Chhikara, Keykavous Parang Copyright (c) 2022 ScienceIn Publishing Wed, 02 Nov 2022 00:00:00 +0000 Synthesis of new regioselective imidazole-isoxazole hybrids as in vitro antibacterial agents <p>The one-pot synthesis of some novel imidazole-isoxazole hybrids<strong> (5a-5n)</strong> and their <em>in vitro</em> antibacterial evaluation against <em>Bacillus </em>subtilis and<em> Staphylococcus aureus </em>was described herein. Among all, compounds <strong>5f</strong>, <strong>5g, 5i </strong>and <strong>5j </strong>displayed greater zone of inhibition on <em>Staphylococcus aureus</em> than the standard streptomycin. Besides, compounds <strong>5f, 5g, 5h, 5i, 5j </strong>and<strong> 5k</strong> displayed higher zone of inhibition towards <em>Bacillus subtilis</em> than the standard. Lastly, minimum inhibitory concentration (MIC) studies of active compounds <strong>5f</strong>, <strong>5g</strong>, <strong>5h</strong>, <strong>5i</strong>, <strong>5j</strong> and <strong>5k </strong>showed that the compounds<strong> 5i </strong>and<strong> 5j</strong> having lesser MIC values on <em>Staphylococcus aureus </em>and<em> Bacillus subtilis </em>than the standard.</p> <p><em>URN:NBN:sciencein.cbl.2022.v9.425</em></p> Sudheer Reddy V, Rajashekar Reddy N, Venkatram Reddy A, Padma M, Krishnakanth Reddy Lelelti Copyright (c) 2022 ScienceIn Publishing Fri, 14 Oct 2022 00:00:00 +0000 Metal based bio-active 1,2,4 triazole derivatives: Preparation, spectral, thermal and antimicrobial studies <p>We report the synthesis and characterization of a series of metal complexes of bivalent Cobalt, Nickel, Copper, Zinc and Palladium with novel Schiff base ligand 4-((4-isopropoxybenzylidene)amino)-5-propyl-4H-3-thiol-1,2,4-triazole (IBPT). The ligand (IBPT) was derived by the condensation reaction of 4-isopropoxybenzaldehyde and 4-amino-5-propyl-3-thiol-1,2,4-triazole and characterised by IR and proton(<sup>1</sup>H) NMR spectroscopic techniques. The complexes have been investigated using characterised Fourier transform infrared (FT-IR), nuclear magnetic resonance (NMR), electron spin resonance (ESR), UV−visible and fluorescence spectroscopies. Based on the comparative analysis of IR and NMR data of ligand and metal complexes, it has been suggested that the ligand chelates with metal ions in a bidentate fashion <em>via</em> N (azomethine) and S (thiol) atoms. Elemental analysis, molar conductance, magnetic moments and redox behaviour of complexes have also been studied. In addition, Tauc's formula has been employed to determine the optical bandgap of complexes using the electronic spectral data. Thermogravimetric analysis revealed the number of coordinated water molecules and thermal stability of metal complexes. Various thermodynamic and kinetic parameters have been evaluated with the help of thermal data using Coats- Redfern method. The octahedral environment of divalent Cobalt, Nickel and Zinc complexes while square planner structure of Copper and Palladium complexes was elucidated with the help of spectroscopic data. Moreover, in-vitro antimicrobial activities of Schiff base ligand and its complexes were estimated against four pathogenic bacterial (two Gram Positive, two Gram negative) and three fungal strains (<em>C. Albicans, A. Niger and A. Clavatus</em>). The biological outcomes ensure the convenient utility of these novel complex as antimicrobial agents.</p> <p><em>URN:NBN:sciencein.cbl.2022.v9.<strong>407</strong></em></p> Kiran Singh, Preeti Siwach Copyright (c) 2022 ScienceIn Publishing Thu, 22 Sep 2022 00:00:00 +0000 Exploring biomarkers associated with secondary inflammation following intracerebral hemorrhage using adult Zebrafish model <p>Intracerebral haemorrhage is the condition of bleeding inside the brain, either spontaneous or traumatic. Though this form of stroke accounts to only about 15% of the cases, the mortality rate is the highest. People with stroke associated with ICH very rarely regain functional independence. The post-stroke complications are due to the extending loss of vascular integrity leading to prolonged secondary inflammation. Early detection of biomarkers associated with the condition and the efficacy of these biomarkers to depict the prognostic rate become essential tools for the clinicians to handle patients with ICH. Development of <em>in vivo</em> models that can simulate the intricate pathophysiology of the condition can add up new biomarkers that serve diagnostic and prognostic purposes.</p> <p><em>URN:NBN:sciencein.cbl.2022.v9.408</em></p> Madhan Kumar Srinivasan, Lalitha Vaidyanathan Copyright (c) 2022 ScienceIn Publishing Thu, 22 Sep 2022 00:00:00 +0000 Design and synthesis of new Nilutamide-1,2,3-triazole derivatives as in vitro Anticancer agents <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> Malla Reddy Nallapu, Rajender Vadluri, Jeyanthi Arasan Copyright (c) 2022 ScienceIn Publishing Wed, 14 Sep 2022 00:00:00 +0000 Plant-derived bioactive compounds in Neuroblastoma therapeutics: Current outlook and future perspective <p>Across the globe, neuroblastoma is responsible for around 15% of child deaths. The cell signaling alterations associated with the disease often result in redundancy and tumor relapse. A plethora of chemotherapeutics, which are already available in the market, are repurposed to treat it. However, they show limited to no efficacy, giving less relief to patients. Systemic toxicities associated with drugs are often linked with comorbidities and result in their discontinuation in clinical settings. Phytochemicals, on the other hand, have come up as an alternative, with the benefits of chemopreventives and fewer side effects. Many preclinical studies using plant-derived compounds have reported molecular targets that suppress neuroblastoma growth with less toxicity. The efficacy of phytochemicals in human trials has led to their approval in clinics. India, being a rich source of biodiversity, inhabits around 11.4% of the floral population of the world. The biologically active compounds extracted from the plants grown in the Indian subcontinent have exhibited high medicinal properties since time immemorial. Our work provides insight into potential phytochemicals, obtained from Indian plants, that can be used to target molecular alterations in neuroblastoma. Besides, Measures to overcome the side effects and low bioavailability of these phytochemicals have also been discussed here.</p> <p><em>URN:NBN:sciencein.cbl.2022.v9.<strong>400</strong></em></p> Nidhi Goswami, Pallavi Sethi, Amar Jyoti, Garima Nagar, Shradheya R.R. Gupta, Archana Singh, Indrakant K. Singh Copyright (c) 2022 ScienceIn Publishing Sun, 25 Sep 2022 00:00:00 +0000 Design, synthesis and molecular docking studies of new Quinoxaline-linked-1,2,4-triazole-Sulfonamide hybrids as Anti-proliferative agents <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> Malla Reddy Nallapu, Rajender Vadluri, Jeyanthi Arasan Copyright (c) 2022 ScienceIn Publishing Mon, 25 Jul 2022 00:00:00 +0000 Medicinal active applications of Dibenzofuran derivatives <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 Sat, 02 Jul 2022 00:00:00 +0000 Investigation of molecular interaction between β-amyloid and insulin receptor: An in-silico study <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> Rakesh Kumar, Niharika, Krishna Kumar Ojha, Harlokesh Narayan Yadav, Nanaocha Sharma, Vijay Kumar Singh Copyright (c) 2022 ScienceIn Publishing Wed, 29 Jun 2022 00:00:00 +0000 Azabicyclononane derivative downregulates the P38 MAP-kinase pathway in colon cancer through apoptosis <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> <p><em>URN:NBN:sciencein.cbl.2022.v9.369</em></p> Bhavapriya Rajendran, Venkatraman Manickam, Ramasamy Tamizhselvi, J Febin PrabhuDass, Sathiyanarayanan Kulathu Iyer, Krishnaraj Thirugnanasambantham, Hairul-Islam Mohamed Ibrahim Copyright (c) 2022 ScienceIn Publishing Sun, 31 Jul 2022 00:00:00 +0000 Lipid based self-assembled nanostructures for therapeutic delivery applications <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 Wed, 01 Jun 2022 00:00:00 +0000 Computational assisted designing, screening, and synthesis of novel Inhibitor of malarial aspartic proteases Plasmepsin I <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 Wed, 22 Jun 2022 00:00:00 +0000 Impact of Ayurvedic drug Tinospora cordifolia in hyperlipidemia induced dysbiosis <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 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 <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 Mon, 16 May 2022 00:00:00 +0000 In Silico analysis of Ceruloplasmin alteration in Oral Squamous Cell Carcinoma <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 Mon, 16 May 2022 00:00:00 +0000