MedChemComm最新文献_第7页

Impact of atropisomerism on a non-steroidal glucocorticoid receptor agonist† 阿托品异构对一种非甾体糖皮质激素受体激动剂的影响

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MedChemComm Pub Date : 2024-05-31 DOI: 10.1039/D4MD00245H

Zhou Xu, Zhongyuan Wang, Xiaona Shi, Rui Ding, Li Han, Xueping Yang, Hongmei Zhang and Adrian D. Hobson

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Systematic computational strategies for identifying protein targets and lead discovery 识别蛋白质靶标和发现先导物的系统计算策略

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MedChemComm Pub Date : 2024-05-31 DOI: 10.1039/D4MD00223G

Arti Kataria, Ankit Srivastava, Desh Deepak Singh, Shafiul Haque, Ihn Han and Dharmendra Kumar Yadav

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Novel flexible biphenyl PfDHFR inhibitors with improved antimalarial activity† 具有更好抗疟活性的新型柔性联苯 PfDHFR 抑制剂

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MedChemComm Pub Date : 2024-05-30 DOI: 10.1039/D4MD00197D

Sasithorn Decharuangsilp, Uthai Arwon, Nawarat Sooksai, Roonglawan Rattanajak, Thanaya Saeyang, Danoo Vitsupakorn, Jarunee Vanichtanankul, Yongyuth Yuthavong, Sumalee Kamchonwongpaisan and Marie Hoarau

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Targeted suppression of oral squamous cell carcinoma by pyrimidine-tethered quinoxaline derivatives† 嘧啶系喹喔啉衍生物对口腔鳞状细胞癌的靶向抑制作用

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MedChemComm Pub Date : 2024-05-24 DOI: 10.1039/D4MD00042K

Asmita Choithramani, Rudradip Das, Gourav Bothra, Priyanka Patel Vatsa, Venkatesh Muthukumar, Bombothu Kavya Sai Bhuvana, Saumya Kapoor, Deepshika Moola, Moumita Ghosh Chowdhury, Amit Mandoli and Amit Shard

{"title":"Targeted suppression of oral squamous cell carcinoma by pyrimidine-tethered quinoxaline derivatives†","authors":"Asmita Choithramani, Rudradip Das, Gourav Bothra, Priyanka Patel Vatsa, Venkatesh Muthukumar, Bombothu Kavya Sai Bhuvana, Saumya Kapoor, Deepshika Moola, Moumita Ghosh Chowdhury, Amit Mandoli and Amit Shard","doi":"10.1039/D4MD00042K","DOIUrl":"10.1039/D4MD00042K","url":null,"abstract":"Oral cancer (OC) stands as a prominent cause of global mortality. Despite numerous efforts in recent decades, the efficacy of novel therapies to extend the lifespan of OC patients remains disappointingly low. Consequently, the demand for innovative therapeutic agents has become all the more pressing. In this context, we present our work on the design and synthesis of twenty-five novel quinoxaline-tethered imidazopyri(mi)dine derivatives. This was followed by comprehensive investigations into the impact of these molecules on the OC cell line. The in vitro cytotoxicity studies performed in CAL-27 and normal oral epithelial (NOE) cell lines revealed that some of the synthesized molecules like 12d have potent antiproliferative activity specifically towards OC cells with an IC50 of 0.79 μM and show negligible cytotoxicity over NOE cells. Further, 12d arrested cell growth in the S phase of the cell cycle and induced cell death by early apoptosis. The in silico studies validated that 12d binds to the activator binding site on pyruvate kinase M2 (PKM2) overexpressed in OC while the lactate dehydrogenase (LDH)-coupled enzyme assay established 12d as a potent PKM2 activator with an AC50 of 0.6 nM. Hence, this study provides fruitful evidence for the designed compounds as anticancer agents against OC.","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 8","pages":" 2729-2744"},"PeriodicalIF":3.597,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141568321","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}

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Identification of lysosomotropism using explainable machine learning and morphological profiling cell painting data† 利用可解释的机器学习和形态剖析细胞绘画数据识别溶酶体运动

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MedChemComm Pub Date : 2024-05-24 DOI: 10.1039/D4MD00107A

Aishvarya Tandon, Anna Santura, Herbert Waldmann, Axel Pahl and Paul Czodrowski

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Fragment-based drug discovery campaigns guided by native mass spectrometry 以原生质谱为指导的片段药物发现活动

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MedChemComm Pub Date : 2024-05-22 DOI: 10.1039/D4MD00273C

Louise M. Sternicki and Sally-Ann Poulsen

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New melphalan derivatives for the treatment of retinoblastoma in combination with thermotherapy† 结合热疗治疗视网膜母细胞瘤的新型美法仑衍生物

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MedChemComm Pub Date : 2024-05-21 DOI: 10.1039/D4MD00211C

Soumaila Zebret, Mouna Hadiji, Jan Romano-deGea, Aurélien Bornet, Daniel Ortiz, Farzaneh Fadaei-Tirani, Christina Stathopoulos, Patrycja Nowak-Sliwinska, Francis L. Munier and Paul J. Dyson

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Current and promising applications of MOF composites in the healing of diabetes wounds MOF 复合材料在糖尿病伤口愈合方面的应用现状和前景

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MedChemComm Pub Date : 2024-05-17 DOI: 10.1039/D4MD00232F

Li-Er Deng, Yuzhi Qiu, Yana Zeng, Jiafeng Zou, Abhinav Kumar, Ying Pan, Alireza Nezamzadeh-Ejhieh, Jianqiang Liu and Xingyan Liu

{"title":"Current and promising applications of MOF composites in the healing of diabetes wounds","authors":"Li-Er Deng, Yuzhi Qiu, Yana Zeng, Jiafeng Zou, Abhinav Kumar, Ying Pan, Alireza Nezamzadeh-Ejhieh, Jianqiang Liu and Xingyan Liu","doi":"10.1039/D4MD00232F","DOIUrl":"10.1039/D4MD00232F","url":null,"abstract":"Diabetes mellitus is an exponentially growing chronic metabolic disease identified by prolonged hyperglycemia that leads to a plethora of health problems. It is well established that the skin of diabetic patients is more prone to injury, and hence, wound healing is an utmost critical restorative process for injured skin and other tissues. Diabetes patients have problems with wound healing at all stages, which ultimately results in delays in the healing process. Therefore, it is vital to find new medications or techniques to hasten the healing of wounds. Metal–organic frameworks (MOFs), an assorted class of porous hybrid materials comprising metal ions coordinated to organic ligands, can display great potential in accelerating diabetic wound healing due to their good physicochemical properties. The release of metal ions during the degradation of MOFs can promote the differentiation of fibroblasts into myofibroblasts and subsequently angiogenesis. Secondly, similar to enzyme-like active substances, they can eliminate reactive oxygen species (ROS) overproduction (secondary to the bio-load of wound bacteria), which is conducive to accelerating diabetic wound healing. Subsequently, MOFs can support the slow release of drugs (molecular or gas therapeutics) in diabetic wounds and promote wound healing by regulating pathological signaling pathways in the wound microenvironment or inhibiting the expression of inflammatory factors. In addition, the combination of photodynamic and photothermal therapies using photo-stimulated porphyrin-based MOF nanosystems has brought up a new idea for treating complicated diabetic wound microenvironments. In this review, recent advances affecting diabetic wound healing, current means of rapid diabetic wound healing, and the limitations of traditional approaches are discussed. Further, the diabetic wound healing applications of MOFs have been discussed followed by the future challenges and directions of MOF materials in diabetic wound healing.","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 8","pages":" 2601-2621"},"PeriodicalIF":3.597,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141531764","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

Molecular understanding of the therapeutic potential of melanin inhibiting natural products 从分子角度了解抑制黑色素的天然产品的治疗潜力

IF 3.597

MedChemComm Pub Date : 2024-05-10 DOI: 10.1039/D4MD00224E

Meijun Pang, Ruitian Xu, Rongjiao Xi, Hong Yao, Kechen Bao, Rui Peng, Hui Zhi, Kuo Zhang, Runnan He, Yanfang Su, Xiuyun Liu and Dong Ming

{"title":"Molecular understanding of the therapeutic potential of melanin inhibiting natural products","authors":"Meijun Pang, Ruitian Xu, Rongjiao Xi, Hong Yao, Kechen Bao, Rui Peng, Hui Zhi, Kuo Zhang, Runnan He, Yanfang Su, Xiuyun Liu and Dong Ming","doi":"10.1039/D4MD00224E","DOIUrl":"10.1039/D4MD00224E","url":null,"abstract":"With the development of society and the improvement of people's living standards, there is an increasing demand for melanin-inhibiting products that prioritize health, safety, and efficacy. Therefore, the development of natural products that can safely and efficiently inhibit melanin synthesis is of great social significance and has significant market potential. In this paper, by reviewing the literature reported in recent years, we summarized the natural products with inhibition of melanin synthesis effects that have been put into or not yet put into the market, and classified them according to the chemical groups of their compounds or the extraction methods of the natural products. Through the summary analysis, we found that these compounds mainly include terpenoids, phenylpropanoids, flavonoids and so on, while the natural product extracts mainly include methanol extracts, ethanol extracts, and aqueous extracts. Their main inhibition of melanin synthesis mechanisms include: (1) direct inhibition of tyrosinase activity; (2) down-regulation of the α-MSH-MC1R, Wnt, NO, PI3K/Akt and MAPK pathways through the expression of MITF and its downstream genes TYR, TRP-1, and TRP-2; (3) antioxidant; (4) inhibition of melanocyte growth through cytotoxicity; (5) inhibition of melanosome production and transport. This paper provides an in-depth discussion on the research progress of whitening natural products and their market value. The aim is to offer guidance for future research and development of natural skin whitening products.","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 7","pages":" 2226-2253"},"PeriodicalIF":3.597,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141147994","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

Deuterium labeling improves the therapeutic index of 3,3′-diselenodipropionic acid as an anticancer agent: insights from redox reactions† 氘标记提高了 3,3′-二硒二丙酸作为抗癌剂的治疗指数：氧化还原反应的启示

IF 3.597

MedChemComm Pub Date : 2024-05-06 DOI: 10.1039/D4MD00105B

V. V. Gandhi, M. K. Pal, B. G. Singh, R. P. Das, A. P. Wadawale, S. Dey and A. Kunwar

{"title":"Deuterium labeling improves the therapeutic index of 3,3′-diselenodipropionic acid as an anticancer agent: insights from redox reactions†","authors":"V. V. Gandhi, M. K. Pal, B. G. Singh, R. P. Das, A. P. Wadawale, S. Dey and A. Kunwar","doi":"10.1039/D4MD00105B","DOIUrl":"10.1039/D4MD00105B","url":null,"abstract":"3,3′-Diselenodipropionic acid (DSePA), a selenocystine derivative, has been previously reported as an oral supplement for anticancer/radio-modulation activities. The present study is focused on devising a strategy to synthesize and characterize the deuterated derivative of DSePA and on understanding the effect of deuteration on its therapeutic index by comparing its cytotoxicity in cancerous versus non-cancerous cell types. In this context, the synthesis of 3,3′-diselenodipropionic acid-D8 (D-DSePA) was accomplished in ∼42% yield. Further, the results clearly established that the deuteration of DSePA significantly reduced its cytotoxicity in non-cancerous cell types while retaining its cytotoxicity in cancerous cell lines. Together, D-DSePA displayed a ∼5-fold higher therapeutic index than the non-deuterated derivative for anticancer activity. The biochemical and NMR studies confirmed that the better biocompatibility of D-DSePA than its non-deuterated derivative in non-cancerous cells was due to its ability to undergo slower redox reactions and to cause lesser inhibition of intracellular redox enzymes.","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 6","pages":" 2165-2178"},"PeriodicalIF":3.597,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141147898","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