Current Chemical Biology最新文献

{"title":"QSAR Docking on Azoles as inhibitors of Notum carboxylesterase","authors":"Amuthalakshmi Sivaperuman, Ramalakshmi Natarajan, Manimegalai P, A. Subramani, Puratchikody Ayarivan","doi":"10.2174/2212796815666211026110125","DOIUrl":"https://doi.org/10.2174/2212796815666211026110125","url":null,"abstract":"\u0000\u0000\u0000Carboxylesterase Notum is a negative regulator of Wnt signaling. Notum carboxylesterase is a carboxylic ester hydrolase enzyme that functions as a negative feedback regulator of Wnt proteins by depalmitoylation reaction. It is of great importance to understand the pathway of Wnt regulation because, conversely, misregulation of Wnt signaling is a telltale sign of cancer and other degenerative diseases. The Wnt inhibition is important in the control of colorectal cancer.\u0000\u0000\u0000\u0000\u0000 In the present study, we carried out a QSAR analysis of a series of reported compounds with carboxylesterase Notum inhibitory activity using multiple regression analysis. A series of 83 compound datasets of pyrrole derivatives with carboxy Notum inhibitory values were taken from the reported literature.\u0000\u0000\u0000\u0000\u0000The study was performed by conducting multiple linear regression analysis followed by validation of the model. The multiple linear regression (MLR) models with the highest coefficients of correlation (R2) and explained variance in leave-one-out (Q2 LOO) prediction and leave-many-out (Q2 LMO) were selected for the whole dataset. The developed models were subjected to internal and external validation. The reliability of the predicted model was checked by plotting the Williams plot. The docking methodology was performed using Autodock 4 for the designed compounds to study the interaction between the ligand and the receptor.\u0000\u0000\u0000\u0000\u0000The best model generated exhibited an r2 value of 0.7413, Q2LOO =0.6379, Q2LMO =0.6368. Novel compounds of phenyl pyrrolidine were designed based on generated QSAR equations. The carboxylesterase Notum inhibitory activity was predicted using the QSAR equations. The docking studies were carried out for designed compounds using Autodock against Carboxylesterase Notum esterase. \u0000\u0000\u0000\u0000\u0000From the results, the designed compounds were found to inhibit Notum Carboxylase. Thus, the study led to the development of a novel lead compound for Carboxylesterase Notum.\u0000","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":"59 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74380247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural compounds as heme oxygenase-1 inducers to reduce the deleterious consequences following SARS-CoV-2 infection","authors":"V. Sorrenti, Valeria Consoli, Salvo Grosso S., L. Vanella","doi":"10.2174/2212796815666211011142101","DOIUrl":"https://doi.org/10.2174/2212796815666211011142101","url":null,"abstract":"\u0000\u0000The virus SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) causes COVID 19 (COronaVIrus Disease 19), a global pandemic with multi-organ failure and resulting in high morbidity and mortality. Some individuals are more vulnerable than others and have deleterious consequences following covid- 19. It has been postulated that Heme oxygenase-1 (HO-1) reduction and free heme may contribute to many of the inflammatory phenomena observed in COVID-19 patients. Therefore, HO-1 inducers could prove to be potential therapeutic or preventive agents for COVID 19. Many of the natural compounds present in fruits and vegetables, such as polyphenols, resulted able to induce HO-1. Aim of this review is to focus on the main foods containing bioactive compounds able to induce HO-1 for an informed choice of foods to use to counteract damage from SARS-CoV-2 infection.\u0000","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":"59 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82991380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meet the Editorial Board Member","authors":"V. Sorrenti","doi":"10.2174/221279681503211230112331","DOIUrl":"https://doi.org/10.2174/221279681503211230112331","url":null,"abstract":"<jats:sec>\u0000<jats:title />\u0000<jats:p />\u0000</jats:sec>","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75930864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meet the Editorial Board Member","authors":"D. Tanini","doi":"10.2174/221279681502210809152428","DOIUrl":"https://doi.org/10.2174/221279681502210809152428","url":null,"abstract":"","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83619020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticarcinogenic Effects of Capsaicin-Loaded Nanoparticles on In vitro Hepatocellular Carcinoma","authors":"N. Hazem, W. Elkashef, I. El-Sherbiny, A. Emam, D. Shaalan, M. Sobh","doi":"10.2174/2212796814999201116211648","DOIUrl":"https://doi.org/10.2174/2212796814999201116211648","url":null,"abstract":"\u0000\u0000Hepatocellular Carcinoma (HCC) is the fifth most frequent cancer worldwide\u0000with a low overall survival due to high metastasis and recurrence rates. The aim of this study\u0000is to assess and compare the possible anti-neoplastic effect of capsaicin and nanoformulated capsaicin\u0000on in vitro HCC human cell line HepG2. The source of the cell line, including when and\u0000from where it was obtained. Whether the cell line has recently been authenticated and by what\u0000method. Whether the cell line has recently been tested for mycoplasma contamination.\u0000\u0000\u0000\u0000 Capsaicin-loaded Trimethyl Chitosan Nanoparticles (CL TMCS NPs)\u0000were synthesized by ionotropic gelation of cationic TMCS with capsaicin. The synthesized nanoparticles\u0000were characterized through TEM, and zeta analyzer. Human hepatocarcinoma HepG2 cell\u0000lines were cultured and treated with 50, 75 & 100 μM of Capsaicin (CAP), plain TMCS NPs and\u0000CL-NPs as well as ethanol (control) for 24h and 48h. The induced effects were investigated by\u0000flow cytometry, immunocytochemistry assay for Bcl-2, Bax, and caspase proteins and evaluating\u0000gene expression levels of Bcl-2, Bax, and MDR-1 mRNA by real-time PCR.\u0000\u0000\u0000\u0000Our results demonstrated that capsaicin- loaded NPs had the potential to significantly increase\u0000capsaicin bioactivity compared with the plain capsaicin formulation either in inducing apoptosis\u0000through altering expression of apoptotic regulators or modifying MDR-1 expression.\u0000\u0000\u0000\u0000TMCs nanoparticles investigated in this study may be a good drug delivery vehicle\u0000for capsaicin. Application of capsaicin-loaded NPs in HCC management as an adjunct therapeutic\u0000approach may be a novel strategy to improve the treatment efficacy and resistance of the conventionally\u0000used chemotherapy.\u0000","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78362830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PEGylated DPPC/Anti-SNAP25 Antibody Targeted Liposomes: From Langmuir Monolayer Study to Formulations","authors":"L. Gew, M. Misran","doi":"10.2174/2212796815666210804111958","DOIUrl":"https://doi.org/10.2174/2212796815666210804111958","url":null,"abstract":"\u0000\u0000Molecule compatibility is an important factor to be considered before preparing antibody-targeted liposomes, stealth-liposomes, and stealth antibody-targeted liposomes.\u0000\u0000\u0000\u0000To determine the intermolecular interaction of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamide-N-[methoxy(polyethyleneglycol)-2000] (ammonium salt), DOPE PEG2000 and Anti-SNAP25 (AS25) in 1,2-dipalmitoyl-sn-glycero-3-phosphorylcholine (DPPC) monolayer, and their liposomes.\u0000\u0000\u0000\u0000In this study, DPPC was used to create a monolayer mimicking the half membrane of liposomes to investigate its interactions with a polyclonal antibody, AS25, and DOPE PEG2000, respectively based on Langmuir-Blodgett (LB) techniques. The surface morphology of DPPC— AS25 and DPPC— DOPE PEG2000— AS25 bilayers were also imaged and analyzed by using atomic force microscopy (AFM) to support the LB findings. The LB findings were then utilized as a reference to prepare DPPC liposomes in this work. \u0000\u0000\u0000\u0000The best mole ratio of DPPCDOPE PEG2000, determined to be 50 to 1, was used to study the interaction with the polyclonal antibody AS25. The free energy of mixing (〖Δ G〗_mix) of DPPC— DOPE PEG2000—AS25 was more negative than DPPC— AS25 in the entire investigated ranges, indicating that the ternary mixture of DPPC— DOPE PEG2000— AS25 was more compatible than the binary mixture of DPPC— AS25. The presence of DOPE PEG2000 in DPPC— AS25 increased the fluidity of the membrane, which resulted in a greater interaction of AS25 with DPPC.\u0000\u0000\u0000\u0000The constant values of particle size and zeta potential measurements of DPPC— DOPE PEG2000— AS25 liposomes showed agreement with the LB findings, indicating that LB is a good technique to predict precise liposomal formulations.\u0000","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":"508 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78143209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational Investigation on the MDM2-Idasanutlin Interaction using the Potential of Mean Force method","authors":"Pundarikaksha Das, V. S. Mattaparthi","doi":"10.2174/2212796815666210716151211","DOIUrl":"https://doi.org/10.2174/2212796815666210716151211","url":null,"abstract":"\u0000\u0000The Murine Double Minute 2 (MDM2) protein is a well-studied primary negative regulator of the tumor suppressor p53 molecule. Therefore, nowadays, many research studies have focused on the inhibition of MDM2 with potent inhibitors. Idasanutlin (RG7388) is a well-studied small molecule, the antagonist of MDM2 with potential antineoplastic activity. Nevertheless, the highly significant information about the free energy profile, intermediates, and the association of receptor and ligand components in the MDM2-idasanutlin complex remains unclear.\u0000\u0000\u0000\u0000To study the free energy profile of the MDM2-idasanutlin complex in terms of the Potential of Mean Force (PMF) method.\u0000\u0000\u0000\u0000We have used the PMF method coupled with umbrella sampling simulations to generate the free energy profile for the association of N-Terminal Domain (NTD) of MDM2 and idasanutlin and a specific reaction coordinate for identifying transition states, intermediates as well as the relative stabilities of the endpoints. We have also determined the binding characteristics and interacting residues at the interface of the MDM2-idasanutlin complex from the Binding Free Energy (BFE) and Per Residue Energy Decomposition (PRED) analyses.\u0000\u0000\u0000\u0000The PMF minima for the MDM2-idasanutlin complex was observed at a center of mass (CoM) distance of separation of 11 Å with dissociation energy of 17.5 kcal mol-1. As a function of the distance of separation of MDM2 from idasanutlin. We also studied the conformational dynamics and stability of the NTD of MDM2. We found a high binding affinity between MDM2 and idasanutlin (∆Grinding = -3.19 kcal mol-1). We found that in MDM2, the residues MET54, VAL67, and LEU58 provide the highest energy input for the interaction between MDM2 and idasanutlin.\u0000\u0000\u0000\u0000Our results in this study illustrate the significant structural and binding features of the MDM2-idasanutlin complex that may be useful in developing potent inhibitors of MDM2.\u0000","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84121181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Seleno-functionalization of BODIPY fluorophores assisted by Oxidative Nucleophilic Hydrogen Substitution","authors":"Beatriz S. Cugnasca, F. Wodtke, A. A. Santos","doi":"10.2174/2212796815666210504084205","DOIUrl":"https://doi.org/10.2174/2212796815666210504084205","url":null,"abstract":"\u0000\u0000Most current reported methods of chalcogen insertion into BODIPY’s nuclei are based on nucleophilic substitution reactions of halogenated derivatives, metal-catalyzed cross-coupling reactions, or assisted by radical mechanisms. Recent reports describe Oxidative Nucleophilic Hydrogen Substitution (ONHS) reactions involving the functionalization of BODIPY nuclei by thiols, but the generalities of the strategy for other chalcogens was not yet demonstrated. Herein we report our contribution on the selenium-functionalization of BODIPY by ONHS, in high yield. \u0000\u0000\u0000\u0000Aryl-Se-functionalization of 2,6-brominated BODIPY’s nuclei by ONHS reaction. \u0000\u0000\u0000\u0000The procedure consists of a direct reaction of 2,6-brominated BODIPYs with in situ generated PhSeH in THF, at room temperature, under a nitrogen atmosphere. The corresponding products were isolated and purified by conventional flash column chromatography. Full structure characterization was performed by 1H, 13C, 19F, and 77Se NMR and DFT calculation. \u0000\u0000\u0000\u0000Densely functionalized 2,6-dibrominated/3,5-diseleno-BODIPYs were obtained, as products, leading to versatile molecular scaffolds, considering their structural features, contrary to initially expected, by the original experimental applied conditions. A mechanistic investigation was performed to conclude that ONHS reaction is governing the transformation to the detriment of nucleophilic substitution of the halogen atoms. \u0000\u0000\u0000\u0000To sum up, new densely functionalized BODIPY derivatives were synthesized by a highly selective, simple, fast, metal-free, and efficient insertion of PhSe- residues into the 3,5-positions, governed by an Oxidative Nucleophilic Hydrogen Substitution (ONHS) reaction, in high yields. It was observed that the presence of halogen (Br) into the 2,6-positions of the BODIPY core is mandatory to the ONHS reaction, which is completely inert when the 2,6-hydrogenated analogues are submitted to the same experimental conditions.\u0000\u0000","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":"49 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80989199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Processes in Cancers and Cancer Chemotherapy","authors":"P. Satya","doi":"10.2174/221279681501210407102624","DOIUrl":"https://doi.org/10.2174/221279681501210407102624","url":null,"abstract":"Progression of several types of cancers, such as prostate cancer, breast cancer, ovarian cancer, pancreatic cancer, colorectal cancer, and a few others, involve complex molecular processes that are not yet well understood. However, current biotechnological methodologies, especially genomic studies, are adding important aspects to this area and for cancer chemotherapy, and thus gene therapy comes as an important approach for therapeutic intervention in tumor. However, some improvements are yet to be developed. Thus, a thematic issue on this topic will be quite timely and will show the directions to researchers to make breakthrough in the area. This thematic issue contains 6 excellent reviews written by highly acclaimed scientists of the field. The very first article entitled “Targeting Protein Degradation in Cancer Treatment” and written by Biij et al. provides extensive comprehension of the ubiquitin proteasome system as a significant process for protein degradation and therefore it can be utilized as promising target for anticancer therapies. In article 2 entitled “Hematological Malignancies: An Overview of the Potential Targets and Their Inhibitors”, Banerjee et al. describe about hematological malignancies pointing out that hematological malignancy single-handedly signifies a cluster of cancer and tumor conditions including leukemia, lymphoma, myeloproliferative neoplasm, lymphoproliferative disorders, etc. Thus, attempts have been made to point out the different proteins involved in hematological malignancies and the different inhibitors and modulating agents of these proteins which can be developed as chemotherapeutic agents against different hematological malignancies. Like article 2, article 3 entitled “Prostaglandin E2 Receptor 4 (EP4): A Promising Therapeutic Target for the Treatment of Cancer and Inflammatory Diseases” and written by Das and Hong describes that prostaglandin E2 (PGE2) is involved in several biological processes including inflammation, pain, fever, renal function, mucosal integrity, angiogenesis and tumor growth. The article specifically points out that PGE2 receptor subtype 4 (EP4) is commonly upregulated in cancer and supports cell proliferation, migration, invasion, and metastasis and therefore the article presents the detail of EP4 receptor and the possible therapeutic applications of its selective agonists and antagonists. Among the cancers, breast cancer has been the most common and highly heterogeneous neoplastic disease comprised of several subtypes with distinct molecular etiology and clinical behaviors. Therefore, Kumar et al. in the article 4 “Understanding Molecular Process and Chemotherapeutics for the Management of Breast Cancer” have presented the promising therapeutic targets and novel anti-cancer approaches emerging from these targets that could be applied clinically in the near future. Following the breast cancer, pancreatic adenocarcinoma (PAC) is the fourth leading cause of cancer-related death over t","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":"42 1","pages":"4-4"},"PeriodicalIF":0.0,"publicationDate":"2021-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87853404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and Antibacterial Activity of New Chalcones Bearing an Imidazo[ 1,2-a]pyridine Moiety","authors":"S. Soltani, S. M. F. Farnia, A. Foroumadi","doi":"10.2174/2212796815666210223110208","DOIUrl":"https://doi.org/10.2174/2212796815666210223110208","url":null,"abstract":"\u0000\u0000 Herein, A series of new imidazo[1,2-a]pyridine-chalcone derivatives\u00003a-m were designed and synthesized to find a new class of antibacterial agents. These compounds\u0000were prepared by the aldol condensation of 2-phenylimidazo[1,2-a]pyridine-3-carbaldehyde\u00002a-b with acetophenone derivatives and other aromatic acetyls. High reaction yields were obtained\u0000in a short reaction time, through applying this multi-step pathway.\u0000\u0000\u0000\u0000In vitro antibacterial activities of the synthesized imidazo[1,2-a]pyridinechalcones\u0000were measured against S. aureus, B. subtilis and E. coli with MIC values of 32 -128\u0000μg/mL. Finally, essential structural analyses such as CHN and NMR spectroscopies were used to\u0000identify the synthesized chalcones based on imidazo[1,2-a]pyridine derivatives.\u0000\u0000\u0000\u0000The results showed that most of the products presented moderate to good antibacterial activities.\u0000Compounds 3b, 3d, 3g, 3l and 3m revealed obvious potency against S. aureus, B. subtilis\u0000and E. coli with MIC values of 32 μg/mL and 64 μg/mL, which were better when compared with\u0000other chalcones.\u0000\u0000\u0000\u0000The synthesized antibacterial compounds were obtained with appealing advantages\u0000such as high purity, simple pathway, good to excellent yields, inexpensive and easy availability of\u0000materials as well as good activities against bacteria. So in this work, a new class of antibacterial\u0000chalcones based on imidazo[1,2-a]pyridine has been reported.\u0000","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75713122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}