Molecular Diversity最新文献_第6页

Design, synthesis, and antibacterial activity of novel amide derivatives containing a sulfone moiety.

IF 3.9 2区化学

Molecular Diversity Pub Date : 2025-02-11 DOI: 10.1007/s11030-024-11088-0

Yue Zou, Xing Liu, Zongnan Zhu, Chao Zhang, Yong Zhang, Yuanzheng Zhao, Xiang Zhu, Jixiang Chen

{"title":"Design, synthesis, and antibacterial activity of novel amide derivatives containing a sulfone moiety.","authors":"Yue Zou, Xing Liu, Zongnan Zhu, Chao Zhang, Yong Zhang, Yuanzheng Zhao, Xiang Zhu, Jixiang Chen","doi":"10.1007/s11030-024-11088-0","DOIUrl":"https://doi.org/10.1007/s11030-024-11088-0","url":null,"abstract":"Twenty-four amide compounds containing a sulfone moiety were synthesized and the antibacterial activity of the target compounds was tested. Some compounds show excellent antibacterial activity. For example, compound AC4 exhibited broad antibacterial activity with the EC50 of 0.55 mg/L for Xanthomonas axonopodis pv. citr (Xac), and 0.48 mg/L for Xanthomonas oryzae pv. oryzae (Xoo). In the greenhouse, compound AC4 with a concentration of 200 mg/L had good protective activity (39.3%) and curative activity (42.2%) against bacterial leaf blight, both were superior to the commercial antibacterial thiodiazole-copper (19.2% and 31.8%) and bismerthiazol (27.4% and 23.1%). The compound AC4 can inhibit the normal growth of Xoo by inhibiting the virality factors of Xoo (motility, exopolysaccharides, and biofilms). At the same time, molecular docking results showed that compound AC4 could interact with exopolysaccharides and quorum sensing-related proteins. This result was further supported by relative gene expression analysis. In addition, the compound AC4 can also increase membrane permeability, induce intracellular reactive oxygen species (ROS) levels to rise, and cause the surface of Xoo to change. The compound AC4 can be further studied as a potential antibacterial agent and this structure will continue to be optimized.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Design and semisynthesis of novel oleanolic acid-based tertiary amide derivatives as promising antifungal agents against phytopathogenic fungi.

IF 3.9 2区化学

Molecular Diversity Pub Date : 2025-02-11 DOI: 10.1007/s11030-025-11123-8

Guoqing Sui, Jiayi Sun, Ailing Zhang, Shuhua Cao, Xiaobo Huang

{"title":"Design and semisynthesis of novel oleanolic acid-based tertiary amide derivatives as promising antifungal agents against phytopathogenic fungi.","authors":"Guoqing Sui, Jiayi Sun, Ailing Zhang, Shuhua Cao, Xiaobo Huang","doi":"10.1007/s11030-025-11123-8","DOIUrl":"https://doi.org/10.1007/s11030-025-11123-8","url":null,"abstract":"To further explore and discover natural products-based antifungal agents, seventeen tertiary amide-oleanolic acid hybrids were designed and synthesized, and structurally confirmed by 1H NMR, 13C NMR, HRMS, and melting point. Bioassay results illustrated that derivative 4 k exhibited prominent in vitro inhibitory activity against the mycelium growth of Gaeumannomyces graminis and Valsa mali with the EC50 values of 41.77 and 43.96 μg/mL, respectively. Meanwhile, the structure-activity relationships were also summarized. Moreover, in vivo control efficacy demonstrated that derivative 4 k displayed remarkable curative effect (CE) against V. mali at 200 μg/mL with the value of 52.6%, evidently superior to that of the positive control carbendazim (41.5%). Besides, derivative 4 k also exhibited good CE against Botrytis cinerea at 200 μg/mL with the value of 33.0%. Scanning electron microscope analysis initially indicated that derivative 4 k may exert its antifungal effect by leading to abnormal morphology on the mycelium surface, resulting in the aberrant hypha growth.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pharmacophore-based identification and in Silico characterization of microbial metabolites as potential modulators of Wnt signaling pathway in colorectal cancer therapy.

IF 3.9 2区化学

Molecular Diversity Pub Date : 2025-02-08 DOI: 10.1007/s11030-024-11103-4

Divya Sharma, Sivakumar Arumugam

{"title":"Pharmacophore-based identification and in Silico characterization of microbial metabolites as potential modulators of Wnt signaling pathway in colorectal cancer therapy.","authors":"Divya Sharma, Sivakumar Arumugam","doi":"10.1007/s11030-024-11103-4","DOIUrl":"https://doi.org/10.1007/s11030-024-11103-4","url":null,"abstract":"Aberrant activation of the Wnt/β-catenin signaling pathway, primarily driven by APC mutation and AXIN degradation via Tankyrase, contributes significantly to colorectal cancer (CRC) progression and metastasis. The accumulation of β-catenin, resulting from the dysregulated ubiquitination, underscores the need for alternative therapeutic strategies targeting Tankyrase and β-catenin. This present study explores microbial metabolites as a source of novel anti-cancer agents, leveraging their unique bioactivity and structural diversity, often exhibiting superior target specificity and lower toxicity than synthetic drugs. Through a computational drug discovery pipeline, a large library of 27641 microbial metabolites was initially screened based on multiple drug-likeliness criteria, resulting in the selection of 2527 compounds. Among the screened compounds, an integrated computational workflow comprising molecular docking, molecular dynamic simulations (MDS), MM/PBSA analysis, and Principal component analysis (PCA) identified Terreustoxin I (T1) as a potential Tankyrase inhibitor. In contrast, compound 10- phenyl-[12]-cytochalasin Z16 (B1) demonstrated a strong binding affinity within the β-catenin active site. Under physiological conditions, these lead compounds were evaluated for conformational stability, binding efficacy, and dynamic behavior. Additionally, ADMET profiling, physiochemical properties, and bioactivity score predictions confirmed the identified compounds' pharmacokinetic suitability and reduced toxicity profile. In silico, cytotoxicity predictions showed significant activity against SW480 and HCT90 colorectal cell lines, with additional anti-neoplastic and anti-leukemic properties, strengthening their candidacy as effective anti-cancer agents. These findings provide a foundation for further experimental validation and development of novel CRC therapies with improved safety and efficacy potential.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Designing a multi-epitope vaccine candidate against pandemic influenza a virus: an immunoinformatics and structural vaccinology approach.

IF 3.9 2区化学

Molecular Diversity Pub Date : 2025-02-08 DOI: 10.1007/s11030-025-11124-7

Mahesh Samantaray, Shilpa Sri Pushan, Muthukumaran Rajagopalan, Kajal Abrol, Jayarani Basumatari, T P Krishna Murthy, Amutha Ramaswamy

{"title":"Designing a multi-epitope vaccine candidate against pandemic influenza a virus: an immunoinformatics and structural vaccinology approach.","authors":"Mahesh Samantaray, Shilpa Sri Pushan, Muthukumaran Rajagopalan, Kajal Abrol, Jayarani Basumatari, T P Krishna Murthy, Amutha Ramaswamy","doi":"10.1007/s11030-025-11124-7","DOIUrl":"https://doi.org/10.1007/s11030-025-11124-7","url":null,"abstract":"Influenza A virus (IAV) remains a significant public health concern due to its annual epidemics and potential for global pandemics. Despite the availability of countermeasures such as vaccines and antiviral treatments, their effectiveness is often questioned due to the emergence of novel strains with antiviral resistance and the variable efficacy of influenza vaccines compared to other vaccines. Traditionally, influenza vaccination strategies have focused on matrix, neuraminidase, and nucleoproteins. In this study, considering the crucial roles of HA and RdRp (PA, PB1, and PB2) of Influenza A, a reverse vaccinology approach is put forth in designing a possible promising antigenic protein toward the development of vaccines against H1N1 viruses. With the development of immunoinformatics approach, one can design/construct potential candidates for vaccine formulation against IAV with the epitope segments identified based on B- and T-cell recognition linked via adjuvants like EAAAK, GPGPG, and AAY linkers. Computational assessments of physicochemical properties, antigenicity, immunogenicity, allergenicity, and toxicity predictions, conducted to evaluate the potential of designed vaccine construct, indicated high antigenicity and potential interactions with immune receptors. Molecular docking of the vaccine construct with human immune receptors (MHCI, MHCII, TLR4, TLR7, and TLR8) followed by molecular dynamics simulations demonstrated stable dynamics with strong binding affinity. The computational immune response modeling with multiple dosages suggested significant immune activation by this construct against IAV. In essence, these findings highlight the potential immune property of the vaccine construct, and put forth the need of thorough preclinical assessments in transforming this construct as a vaccine against the challenging IAV pathogens.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Click Chemistry: an overview and recent updates in the medicinal attributes of click-derived heterocycles.

IF 3.9 2区化学

Molecular Diversity Pub Date : 2025-02-07 DOI: 10.1007/s11030-025-11110-z

Poonam Bishnoi, Bhavna Saroha, Suresh Kumar, Gourav Kumar, Arpana Bhardwaj, Meena Kumari, Naveen Kumar

{"title":"Click Chemistry: an overview and recent updates in the medicinal attributes of click-derived heterocycles.","authors":"Poonam Bishnoi, Bhavna Saroha, Suresh Kumar, Gourav Kumar, Arpana Bhardwaj, Meena Kumari, Naveen Kumar","doi":"10.1007/s11030-025-11110-z","DOIUrl":"https://doi.org/10.1007/s11030-025-11110-z","url":null,"abstract":"Recently, it has been seen that there is a rapid surge in Click Chemistry (CC) research owing to its fast, reliable, and biocompatible nature, making it an ideal tool for drug discovery. CC approach allows facile and sustainable development of complex molecules with minimal off-target products. With the rapid advancement of the CC field, its applications have significantly expanded across various domains, including biomedical, pharmaceutical, radiochemistry, nanochemistry, polymer chemistry, and microscopy. However, its applications remain most prominent in medicinal chemistry. This review initially covers the introduction and distinct types of click reactions such as copper-catalyzed azide-alkyne cycloaddition (CuAAC), strain-promoted azide-alkyne cycloaddition (SPAAC), and Diels-Alder Cycloaddition (DA), followed by the different techniques facilitating the click reactions. Among these, the CuAAC reaction is most effective and extensive CC approach widely explored for creating huge number of molecular libraries of medicinal significance due to its excellent biocompatibility, reliability, and specificity. In this review, we mainly included the synthesis and medicinal attributes of click reaction (CuAAC & SPAAC)-derived organic heterocycles from 2012-2023, particularly anticancer, antiviral, antidiabetic, and antimicrobial that will help the readers to understand the concept of CC, medicinal significance of CC-derived heterocycles, unexplored areas, challenges, and future prospects. This review will also provide a roadmap for new research directions and applications of click-derived heterocycles in medicinal chemistry.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In silico screening of natural compounds as potential inhibitors against SecA protein of Acinetobacter baumannii.

IF 3.9 2区化学

Molecular Diversity Pub Date : 2025-02-07 DOI: 10.1007/s11030-024-11097-z

Aishwarya Swain, Smruti Sikha Senapati, Archana Pan

{"title":"In silico screening of natural compounds as potential inhibitors against SecA protein of Acinetobacter baumannii.","authors":"Aishwarya Swain, Smruti Sikha Senapati, Archana Pan","doi":"10.1007/s11030-024-11097-z","DOIUrl":"https://doi.org/10.1007/s11030-024-11097-z","url":null,"abstract":"SecA protein is a vital protein in bacterial protein transport systems and has been reported as a promising drug target in various bacteria, including the multidrug-resistant Acinetobacter baumannii for which development of novel drugs are urgently needed. To this end, the present study aims to screen natural compounds as potential inhibitors against SecA protein of this pathogen. Initially, structural modeling of SecA protein was performed to generate multiple models, which were assessed using various criteria. The most reliable model, Rank3 from AlphaFold2, was selected for molecular dynamics (MD) simulation study to obtain an energy-minimized structure. Virtual screening of this energy-minimized structure against the natural compound databases (LOTUS and CMNPD) identified five natural compounds, namely TCC, TMX, DDA, PF, and DOP with docking scores of - 9.801 kcal/mol, - 9.565 kcal/mol, - 9.092 kcal/mol, - 8.862 kcal/mol, and - 8.758 kcal/mol, respectively, which were significantly better than those of known SecA inhibitors CJ-21058 (- 3.92 kcal/mol), Pannomycin (- 3.234 kcal/mol), and Rose Bengal (- 2.608 kcal/mol). MD simulation studies confirmed the stability of protein-ligand complexes for all five compounds. Although DOP demonstrated the strongest binding energy (ΔG = - 46.93 ± 6.11 kcal/mol), it was excluded as it could cause respiratory toxicity and eye irritation. TMX, on the other hand, showed significant binding energy (ΔG = - 38.23 ± 2.97 kcal/mol), complex stability, good bioavailability, and an acceptable safety profile, indicating it as a potential inhibitor against SecA protein. Thus, our study uncovers a natural compound TMX as a potential inhibitor against a specific target protein. This can be further explored for experimental validation to develop novel drugs against the infectious diseases caused by A. baumannii/other related clinically important pathogens.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Metagenomic analysis and proteins prediction of emerging pathogens in artisanal cheese.

IF 3.9 2区化学

Molecular Diversity Pub Date : 2025-02-06 DOI: 10.1007/s11030-025-11116-7

Wemerson de Castro Oliveira, Pedro Henrique Marques, Magnolia Martins Erhardt, Andrei Giacchetto Felice, Caio Luigi Antunes Moura Tristão, Flavia Figueira Aburjaile, Maria Beatriz Prior Pinto Oliveira, Neila Silvia Pereira Dos Santos Richards

{"title":"Metagenomic analysis and proteins prediction of emerging pathogens in artisanal cheese.","authors":"Wemerson de Castro Oliveira, Pedro Henrique Marques, Magnolia Martins Erhardt, Andrei Giacchetto Felice, Caio Luigi Antunes Moura Tristão, Flavia Figueira Aburjaile, Maria Beatriz Prior Pinto Oliveira, Neila Silvia Pereira Dos Santos Richards","doi":"10.1007/s11030-025-11116-7","DOIUrl":"https://doi.org/10.1007/s11030-025-11116-7","url":null,"abstract":"Currently, reports of the presence of emerging pathogens in cheeses are low and new outbreaks have occurred at an alarming rate, with the Vibrio and Aeromonas genera being the main causes of gastroenteritis in the world. Therefore, Multi-Omics integration has been a strategy to identify and develop detection methods for these pathogens in food. We investigated the presence of emerging pathogens in artisanal cheeses and predicted proteins with immunogenic potential, in silico, for food diagnostics. For this, multiomics integration was used: (a) metagenomics; (b) subtractive genomics; and (c) pan-genomics. Eight species of the genera Vibrio and Aeromonas were identified, the latter being the most abundant (89.7%) and identified in eight regions, with emphasis on the species A. caviae and A. veronii. Pan-genomic analyses revealed intra- and inter-species differences in both genera. Essential, non-cytoplasmic proteins were identified, without homology and with immunological potential for the species researched. Functional annotation of genes present in pan-genomic subsets reveals functionality between the core genome (transcription; amino acid transport and metabolism; and inorganic ion transport and metabolism) and the shared genome (signal transduction and carbohydrate transport and metabolism). A reinterpretation of the genomic plasticity of V. furnissii reveals the presence of mobile genetic elements critical for virulence in human isolates and the RTX toxin, also identified in this species, is present in the pathogenicity islands of V. alginolyticus and V. fluvialis. Collectively, the results provide important information for the development of a diagnostic strategy for emerging pathogens in food using immunoassays.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

1-Styryl-1,3-diketones in the synthesis of spiro[oxindole-3,2'-pyrrolidines] with notable anticancer activity.

IF 3.9 2区化学

Molecular Diversity Pub Date : 2025-02-04 DOI: 10.1007/s11030-024-11099-x

Nikolay S Zimnitskiy, Vladislav Y Korotaev, Maria V Ulitko, Vyacheslav Y Sosnovskikh

引用次数: 0

Reductive coupling of 2,2'-dinitrobiphenyls into benzo[c]cinnolines with NaHS.

IF 3.9 2区化学

Molecular Diversity Pub Date : 2025-02-04 DOI: 10.1007/s11030-024-11087-1

Pingbing Yu, Zhaoyue Wen, Chun Wang, Jianlian Wu, Tie-Gen Chen, Wei Chen

引用次数: 0

Evaluation of selected indigenous spices- and herbs-derived small molecules as potential inhibitors of SREBP and its implications for breast cancer using MD simulations and MMPBSA calculations.

IF 3.9 2区化学

Molecular Diversity Pub Date : 2025-02-03 DOI: 10.1007/s11030-025-11122-9

Urvashi Tiwari, Salman Akhtar, Snober S Mir, Mohammad Kalim Ahmad Khan

{"title":"Evaluation of selected indigenous spices- and herbs-derived small molecules as potential inhibitors of SREBP and its implications for breast cancer using MD simulations and MMPBSA calculations.","authors":"Urvashi Tiwari, Salman Akhtar, Snober S Mir, Mohammad Kalim Ahmad Khan","doi":"10.1007/s11030-025-11122-9","DOIUrl":"https://doi.org/10.1007/s11030-025-11122-9","url":null,"abstract":"In this study, we conducted an extensive analysis of 252 bioactive compounds derived from native spices and herbs for their potential anti-breast cancer activity against sterol regulatory element-binding protein (SREBP), using in silico techniques. To evaluate the oral bioavailability, overall pharmacokinetics, and safety profiles of these compounds, we employed Lipinski's rule of five and ADME descriptors, which depicted 66 lead molecules. These molecules were then docked with the SREBP using molecular docking tools, which revealed that diosgenin and smilagenin were the most promising hits compared to the reference inhibitor betulin, with average binding affinities of - 7.42 and - 7.37 kcal/mol and - 6.27 kcal/mol, respectively. To further assess the stability of these complexes along with betulin, we conducted molecular dynamics simulations over a 100 ns simulation period. We employed various parameters, including the root-mean-square deviation, root-mean-square fluctuation, solvent-accessible surface area, free energy of solvation, and radius of gyration, followed by principal component analysis. Furthermore, we evaluated the toxicity of the selected compounds against various anticancer cell lines, as well as their metabolic activity related to CYP450 metabolism and biological activity spectrum. Based on these results, both molecules exhibited promising drug candidate potential and could be utilized for further experimental analysis to elucidate their anticancer potential.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0