MedChemComm最新文献_第6页

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

IF 3.597

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

IF 3.597

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

IF 3.597

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

IF 3.597

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}

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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}

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Unveiling the potent activity of a synthetic ion transporter against multidrug-resistant Gram-positive bacteria and biofilms† 揭示合成离子转运体对耐多药革兰氏阳性菌和生物膜的强效活性

IF 3.597

MedChemComm Pub Date : 2024-05-03 DOI: 10.1039/D4MD00002A

Sudip Mukherjee, Sopan Valiba Shinde, Pinaki Talukdar and Jayanta Haldar

{"title":"Unveiling the potent activity of a synthetic ion transporter against multidrug-resistant Gram-positive bacteria and biofilms†","authors":"Sudip Mukherjee, Sopan Valiba Shinde, Pinaki Talukdar and Jayanta Haldar","doi":"10.1039/D4MD00002A","DOIUrl":"10.1039/D4MD00002A","url":null,"abstract":"The increasing prevalence of drug-resistant infections caused by Gram-positive bacteria poses a significant threat to public healthcare. These pathogens exhibit not only smart resistance mechanisms but also form impenetrable biofilms on various surfaces, rendering them resilient to conventional therapies. In this study, we present the potent antibacterial activity of a synthetic ion transporter T against multi-drug resistant (MDR) Gram-positive pathogens, with minimum inhibitory concentration (MIC) values ranging from 0.5 to 2 μg mL−1. The compound demonstrates high selectivity with negligible toxicity towards mammalian cells (HC50 = 810 μg mL−1). It exhibits fast killing kinetics, completely eliminating >5 log bacterial cells within 12 h. Moreover, the compound displays efficacy against both planktonic bacteria and preformed biofilms of methicillin-resistant S. aureus (MRSA), reducing the bacterial burden within the biofilm by 2 log. Mechanistic investigations reveal that the ion transporter depolarizes the bacterial membrane potential and enhances membrane permeability. Additionally, it generates reactive oxygen species, contributing to its bactericidal activity. Notably, MRSA did not exhibit detectable resistance to the ion transporter even after serial passaging for 10 days. Collectively, this novel class of ion transporter holds promise as a therapeutic candidate for combating infections caused by multi-drug resistant Gram-positive bacteria.","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 6","pages":" 2127-2137"},"PeriodicalIF":3.597,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141062084","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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Photodynamic treatment of Staphylococcus aureus with non-iron hemin analogs in the presence of hydrogen peroxide† 在过氧化氢存在下用非铁血氨类似物对金黄色葡萄球菌进行光动力治疗

IF 3.597

MedChemComm Pub Date : 2024-05-03 DOI: 10.1039/D4MD00148F

Badhu Prashanthika Sivasubramaniam, Benjamin M. Washer, Yuichiro Watanabe, Kathryn E. Ragheb, J. Paul Robinson and Alexander Wei

{"title":"Photodynamic treatment of Staphylococcus aureus with non-iron hemin analogs in the presence of hydrogen peroxide†","authors":"Badhu Prashanthika Sivasubramaniam, Benjamin M. Washer, Yuichiro Watanabe, Kathryn E. Ragheb, J. Paul Robinson and Alexander Wei","doi":"10.1039/D4MD00148F","DOIUrl":"10.1039/D4MD00148F","url":null,"abstract":"Bacteria subjected to antiseptic or antibiotic stress often develop tolerance, a trait that can lead to permanent resistance. To determine whether photodynamic agents could be used to counter tolerance, we evaluated three non-iron hemin analogs (M-PpIX; M = Al, Ga, In) as targeted photosensitizers for antimicrobial photodynamic inactivation (aPDI) following exposure to sublethal H2O2. Al-PpIX is an active producer of ROS whereas Ga- and In-PpIX are more efficient at generating singlet oxygen. Al- and Ga-PpIX are highly potent aPDI agents against S. aureus and methicillin-resistant strains (MRSA) with antimicrobial activity (3 log reduction in colony-forming units) at nanomolar concentrations. The aPDI activities of Al- and Ga-PpIX against S. aureus were tested in the presence of 1 mM H2O2 added at different stages of growth. Bacteria exposed to H2O2 during log-phase growth were less susceptible to aPDI but bacteria treated with H2O2 in their postgrowth phase exhibited aPDI hypersensitivity, with no detectable colony growth after treatment with 15 nM Ga-PpIX.","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 6","pages":" 2138-2145"},"PeriodicalIF":3.597,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/md/d4md00148f?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141062087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0