Exploration of drug science最新文献_第4页

A dextrorotatory residues-incorporated bioactive dodecapeptide against enterohemorrhagic Escherichia coli 抗肠出血性大肠杆菌的右旋残渣结合生物活性十二肽

Exploration of drug science Pub Date : 2023-06-30 DOI: 10.37349/eds.2023.00014

Ping Zeng, Xuemei Yang, K. Wong, Sheng Chen, Kin-Fai Chan, S. Leung, Lanhua Yi

{"title":"A dextrorotatory residues-incorporated bioactive dodecapeptide against enterohemorrhagic Escherichia coli","authors":"Ping Zeng, Xuemei Yang, K. Wong, Sheng Chen, Kin-Fai Chan, S. Leung, Lanhua Yi","doi":"10.37349/eds.2023.00014","DOIUrl":"https://doi.org/10.37349/eds.2023.00014","url":null,"abstract":"Aim: This study aims to report an engineered peptide zp39 with favorable bioactivity against enterohemorrhagic Escherichia coli (E. coli, EHEC). Its antibacterial mechanisms and application in a real food system are assessed.\u0000Methods: Spatial conformation of synthetic peptide zp39 (GIIAGIIiKIKk-NH2, lowercase letters indicate dextrorotatory amino acids) was predicted by PEPstrMOD and its secondary structure was further determined by circular dichroism (CD) spectroscopy. Then, standard E. coli O157:H7 strain ATCC 43888 was used to evaluate the bioactivity of zp39. A double dilution method was applied to investigate its efficacy in normal broth medium, serum, and highly saline conditions. Its effects on cell membrane permeability and potential were measured by fluorescent assays. Thereafter, morphological changes of E. coli O157:H7 cells were monitored by electron microscopy technologies. Finally, the potential application of zp39 in controlling EHEC in food was tested with spinach juice and the Galleria mellonella larvae model was employed to assess the in vivo efficacy.\u0000Results: Peptide zp39 presented an amphiphilic helical structure. It effectively inhibited the growth of E. coli O157:H7 at a concentration of 4 μmol/L in a bactericidal mode. Mechanistic studies revealed that it affected membrane permeability and potential in a dose-dependent manner. Moreover, zp39 maintained satisfactory bioactivity against E. coli O157:H7 even in the presence of 70% serum or 1,000 μmol/L chloride salts. In spinach juice application, > 90% E. coli O157:H7 cells were killed within 2 h after exposure to 64 μmol/L zp39. In vivo study proved that treatment with 64 μmol/L zp39 could effectively boost the survival ratio of infected larvae by 50%.\u0000Conclusions: This study depicts a synthetic dodecapeptide that shows the potential application in controlling EHEC. This molecule may be developed into a highly effective antimicrobial agent applied to prevent food contamination and associated infections.","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83172877","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}

引用次数: 0

Identification of an inter-cysteine loop potentially involved in the activity of Opisthorchis viverrini-granulin-1 半胱氨酸间环的鉴定可能参与了蛇胸菌颗粒蛋白-1的活性

Exploration of drug science Pub Date : 2023-06-30 DOI: 10.37349/eds.2023.00012

R. Takjoo, David T. Wilson, P. Bansal, A. Loukas, M. Smout, N. Daly

{"title":"Identification of an inter-cysteine loop potentially involved in the activity of Opisthorchis viverrini-granulin-1","authors":"R. Takjoo, David T. Wilson, P. Bansal, A. Loukas, M. Smout, N. Daly","doi":"10.37349/eds.2023.00012","DOIUrl":"https://doi.org/10.37349/eds.2023.00012","url":null,"abstract":"Aim: Identification of small bioactive regions in proteins and peptides can be useful information in drug design studies. The current study has shown that an inter-cysteine loop of the N-terminal domain of Opisthorchis viverrini granulin-1 (Ov-GRN-1), a granulin protein from the flatworm liver fluke Opisthorchis viverrini which has potent wound healing properties, maintains the bioactivity of the full-length protein.\u0000Methods: Peptides corresponding to the three inter-cysteine loops of the N-terminal domain were produced using synthetic chemistry, and their structures and bioactivities were analyzed using nuclear magnetic resonance (NMR) spectroscopy and cell proliferation assays, respectively.\u0000Results: As expected for such small peptides, NMR analysis indicated that the peptides were poorly structured in solution. However, a seven-residue peptide corresponding to loop 2 (GRN-L2) promoted cell proliferation, in contrast to the other fragments.\u0000Conclusions: The results from the current study suggest that GRN-L2 might be responsible, in part, for the bioactivity of Ov-GRN-1, and might be a useful lead molecule for subsequent wound healing studies.","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80991920","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}

引用次数: 0

Nature-inspired and medicinally relevant short peptides 自然启发和医学相关的短肽

Exploration of drug science Pub Date : 2023-06-27 DOI: 10.37349/eds.2023.00011

M. G. Ciulla, M. Civera, S. Sattin, Kamal Kumar

{"title":"Nature-inspired and medicinally relevant short peptides","authors":"M. G. Ciulla, M. Civera, S. Sattin, Kamal Kumar","doi":"10.37349/eds.2023.00011","DOIUrl":"https://doi.org/10.37349/eds.2023.00011","url":null,"abstract":"Peptides constitute an important component of Nature’s pharmacy and they play a significant role in several signaling pathways acting as natural biological messengers. While nature has mastered the cycle of creation, application, and destruction of large and short peptides to the benefit of the host organism, organic and medicinal chemists have in their capacity and small steps, made big developments in the field of peptide synthesis as well as in developing them as therapeutics. In comparison to their big counterparts, i.e. proteins, short peptides encompass several advantages, from the ease of synthesis to their physico-chemical properties. However, the real challenge for in vivo application of therapeutic peptides is to overcome their low plasma availability and their fast enzymatic degradation. This review briefly covers the relevant areas of medicinally important short peptides and the recent developments made to turn these peptides into therapeutics. Also presented in this article are important efforts and strategies used to overcome some of the inherent limitations of peptidic molecules and thereby facilitate their progression in the clinical phases towards approved drugs.","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"220 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88025246","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}

引用次数: 1

Heterogeneous graph convolutional neural network for protein-ligand scoring 蛋白质配体评分的异构图卷积神经网络

Exploration of drug science Pub Date : 2023-04-30 DOI: 10.37349/eds.2023.00010

Kevin Crampon, Alexis Giorkallos, X. Vigouroux, S. Baud, L. Steffenel

{"title":"Heterogeneous graph convolutional neural network for protein-ligand scoring","authors":"Kevin Crampon, Alexis Giorkallos, X. Vigouroux, S. Baud, L. Steffenel","doi":"10.37349/eds.2023.00010","DOIUrl":"https://doi.org/10.37349/eds.2023.00010","url":null,"abstract":"Aim: Drug discovery is a long process, often taking decades of research endeavors. It is still an active area of research in both academic and industrial sectors with efforts on reducing time and cost. Computational simulations like molecular docking enable fast exploration of large databases of compounds and extract the most promising molecule candidates for further in vitro and in vivo tests. Structure-based molecular docking is a complex process mixing both surface exploration and energy estimation to find the minimal free energy of binding corresponding to the best interaction location.\u0000Methods: Hereafter, heterogeneous graph score (HGScore), a new scoring function is proposed and is developed in the context of a protein-small compound-complex. Each complex is represented by a heterogeneous graph allowing to separate edges according to their class (inter- or intra-molecular). Then a heterogeneous graph convolutional network (HGCN) is used allowing the discrimination of the information according to the edge crossed. In the end, the model produces the affinity score of the complex.\u0000Results: HGScore has been tested on the comparative assessment of scoring functions (CASF) 2013 and 2016 benchmarks for scoring, ranking, and docking powers. It has achieved good performances by outperforming classical methods and being among the best artificial intelligence (AI) methods.\u0000Conclusions: Thus, HGScore brings a new way to represent protein-ligand interactions. Using a representation that involves classical graph neural networks (GNNs) and splitting the learning process regarding the edge type makes the proposed model to be the best adapted for future transfer learning on other (protein-DNA, protein-sugar, protein-protein, etc.) biological complexes.","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"50 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85736473","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}

引用次数: 0

Nano theranostics involved in bladder cancer treatment 纳米疗法在膀胱癌治疗中的应用

Exploration of drug science Pub Date : 2023-04-28 DOI: 10.37349/eds.2023.00008

Kun Liu, Qixin Mo, Z. Ding, Shicong Lai, Jian Ren, Qingsong Yu

引用次数: 0

Machine learning for drug science 药物科学的机器学习

Exploration of drug science Pub Date : 2023-04-16 DOI: 10.37349/eds.2023.00007

de Azevedo Jr. Walter F.

引用次数: 0

Levistolide A and periplogenin inhibit the growth of gastric cancer cells in vitro and in vivo 列维stolide A和periplogenin对胃癌细胞生长有体外和体内抑制作用

Exploration of drug science Pub Date : 2023-03-30 DOI: 10.37349/eds.2023.00006

Jiaqian Guo, Hongshang Hu, S. Lee, Ji Zhong Zhao

{"title":"Levistolide A and periplogenin inhibit the growth of gastric cancer cells in vitro and in vivo","authors":"Jiaqian Guo, Hongshang Hu, S. Lee, Ji Zhong Zhao","doi":"10.37349/eds.2023.00006","DOIUrl":"https://doi.org/10.37349/eds.2023.00006","url":null,"abstract":"Aim: In the present study, the natural products levistolide A (LA) and periplogenin (PPG) were studied for their growth inhibitory effects on the development of gastric cancer cells in vitro and, more critically, in vivo, alone or in combination with the therapeutic medication 5-fluorouracil (5-FU).\u0000Methods: Methyl thiazolyl tetrazolium (MTT), also known as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assays were used for the cell viability study. Apoptosis was detected by western blot to detect the cleavage of caspase substrate poly (ADP-ribose) polymerase (PARP) and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick-end labelling (TUNEL) assays. The nude mice bearing gastric cancer cells were used for the anti-cancer activity detection of LA and its combinational treatment effect with 5-FU.\u0000Results: The results in the present study shown that the two compounds were able to inhibit the viability of the cancer cells in a dose- and time-dependent manner by MTT method. They could trigger apoptosis when used alone, and more potently, in combination with 5-FU detected by TUNEL positivity and the cleavage of caspase substrate PARP. In nude mice bearing gastric cancer cells, injection (i.p.) of LA or PPG alone inhibited the growth of the cancer cells. The treatment using one of the compounds in combination with 5-FU inhibited the cancer cell growth at a higher level than the treatment by a compound alone.\u0000Conclusions: LA and PPG could inhibit the growth of the cancer cells, alone or in combination with 5-FU, in vitro and in vivo, suggesting that they are promising investigational drugs for therapeutic development.","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82963079","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}

引用次数: 0

Essential functions, syntheses and detection of sialyl Lewis X on glycoproteins 唾液酸Lewis X对糖蛋白的基本功能、合成及检测

Exploration of drug science Pub Date : 2023-02-28 DOI: 10.37349/eds.2023.00004

Qiu-Chen Chen, Han Liu, Xuechen Li

引用次数: 1

Surface functionalized mesoporous polydopamine nanocomposites for killing tumor cells through collaborative chemo/photothermal/chemodynamic treatment 表面功能化介孔聚多巴胺纳米复合材料通过协同化疗/光热/化学动力学治疗杀死肿瘤细胞

Exploration of drug science Pub Date : 2023-02-27 DOI: 10.37349/eds.2023.00003

Yi Ouyang, Yan Chen, Ting Xu, Yi Sun, Shenghe Zhao, Chunmei Chen, Yixin Tan, Liang He, Hui Liu

{"title":"Surface functionalized mesoporous polydopamine nanocomposites for killing tumor cells through collaborative chemo/photothermal/chemodynamic treatment","authors":"Yi Ouyang, Yan Chen, Ting Xu, Yi Sun, Shenghe Zhao, Chunmei Chen, Yixin Tan, Liang He, Hui Liu","doi":"10.37349/eds.2023.00003","DOIUrl":"https://doi.org/10.37349/eds.2023.00003","url":null,"abstract":"Aim: The development of a collaborative strategy with improved efficacy holds great promise in tumor treatment. This study aims to develop an effective collaborative strategy based on functionalized mesoporous polydopamine (MPDA) nanocomposites for killing tumor cells.\u0000Methods: MPDA nanoparticles were synthesized and functionalized with camptothecin (CPT) payload and manganese dioxide (MnO2) coating to construct MPDA-CPT-MnO2 nanocomposites.\u0000Results: When uptaken by tumor cells, the nanocomposites can degrade to produce O2, release CPT, and generate manganese (Mn2+) under the stimulation of hydrogen peroxide (H2O2) and acid. The released CPT and Mn2+ can act as chemotherapeutic drug and Fenton-like agent, respectively. Abundant reactive oxygen species (ROS) are generated in 4T1 tumor cells through an Mn2+-mediated Fenton-like reaction. After that, the generated Mn4+ can react with glutathione (GSH) through redox reaction to produce Mn2+ and deplete GSH, disrupting the reducing capacity and benefiting the production of ROS in tumor cells. Under laser irradiation, the nanocomposites can generate hyperthermia to promote the production of ROS.\u0000Conclusions: The developed MPDA-CPT-MnO2 nanocomposites can kill tumor cells through collaborative chemo/photothermal/chemodynamic therapy (CDT).","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"91 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82088657","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}

引用次数: 0

Convenient estimation of oxytetracycline and polymyxin B by a novel high-performance liquid chromatography method: development and validation 新型高效液相色谱法测定土霉素和多粘菌素B的方法:建立与验证

Exploration of drug science Pub Date : 2023-02-24 DOI: 10.37349/eds.2023.00002

T. Chaudhary, Kurmi Balak Das, Dilpreet K Singh

{"title":"Convenient estimation of oxytetracycline and polymyxin B by a novel high-performance liquid chromatography method: development and validation","authors":"T. Chaudhary, Kurmi Balak Das, Dilpreet K Singh","doi":"10.37349/eds.2023.00002","DOIUrl":"https://doi.org/10.37349/eds.2023.00002","url":null,"abstract":"Aim: The aim of this research work was to develop a validated reversed-phase (RP)-high-performance liquid chromatography (HPLC) method for simultaneous estimation of oxytetracycline (OXY) and polymixin B (PMB) in fixed-dose combination.\u0000Methods: The HPLC assay method was validated on X-Bridge C18 [250 mm × 4.6 mm intradermal (i.d.), 5 μm], mobile phase consisting of aotearoa co-incidence network (ACN):water containing 0.5% (v/v) orthophosphoric acid (pH 3.5) in the ratio of 80:20 respectively. The flow rate was set at 0.9 mL/min and the column was maintained at room temperature. The RP-HPLC method was validated in terms of the calibration curve (CC), linearity and range, limit of detection (LOD), and limit of quantitation (LOQ), precision, robustness, and accuracy.\u0000Results: The method was found to be linear with a concentration range of 5–25 µg/mL. Precision results showed the developed method was found to be precise with a relative standard deviation [RSD (%)] value < 2. Accuracy showed acceptable recovery of prepared concentrations as per intracerebral hemorrhage (ICH) guidelines. Moreover, the developed method was found to be robust and rugged, as per specified ranges. The assay of these two drugs in marketed formulation, i.e., Terramycin® Ointment showed satisfactory recovery, as per ICH guidelines. The results proved that the method can be used for the routine-based estimation of OXY and PMB.\u0000Conclusions: Linear CC were obtained with a correlation coefficient (R2 > 0.99) with acceptable results of accuracy and precision.","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74290332","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}

引用次数: 0