IF 3.4 4区医学

ChemMedChem Pub Date : 2025-09-29 DOI: 10.1002/cmdc.70056

Anoopjit Singh Kooner, Mariah Norman, Igi Vilza, Michael P. Mannino, Mary Savari Dhason, Jon Helander, Shrushti Patil, L. David Sibley, James W. Janetka

引用次数: 0

pH-Responsive Nanoscale Mixed Ligand Metal Organic Framework as a Carrier for Photosensitizer in Targeted Antibacterial Photodynamic Therapy. ph响应纳米级混合配体金属有机骨架作为光敏剂载体在靶向抗菌光动力治疗中的应用。

IF 3.4 4区医学

ChemMedChem Pub Date : 2025-09-28 DOI: 10.1002/cmdc.202500510

Fathima Fasna P H, Sreesha Sasi, Hareesh N Ramanathan, Jasna Vijayan, Mohamed Hatha Abdulla Ammanamveetil

{"title":"pH-Responsive Nanoscale Mixed Ligand Metal Organic Framework as a Carrier for Photosensitizer in Targeted Antibacterial Photodynamic Therapy.","authors":"Fathima Fasna P H, Sreesha Sasi, Hareesh N Ramanathan, Jasna Vijayan, Mohamed Hatha Abdulla Ammanamveetil","doi":"10.1002/cmdc.202500510","DOIUrl":"https://doi.org/10.1002/cmdc.202500510","url":null,"abstract":"The escalating multidrug-resistant bacterial infections underscore the urgent need for alternatives to conventional antibiotics. Antimicrobial photodynamic therapy emerges as a promising strategy, leveraging light-activated photosensitizers like methylene blue (MB) to generate bactericidal reactive oxygen species (ROS) that disrupt microbial membranes and DNA. This approach minimizes resistance development due to the nonspecific action of ROS and demonstrates efficacy against both Gram-positive and Gram-negative pathogens. A pH-responsive mixed-ligand metal-organic framework (ML-MOF) is synthesized as a nanocarrier for MB. Encapsulation of MB into ML-MOF (MB@ML-MOF50) resulted in a loading capacity of 29.67%, with a controlled and sustained release profile of 85% at pH 5.1 (infection-mimicking conditions). MB@ML-MOF50 exhibited twice the singlet oxygen generation efficiency (S = 0.2098) compared to free MB (S = 0.1058), confirming enhanced photodynamic activity. MB@ML-MOF50 under 650 nm laser irradiation achieved complete bacterial inhibition (0% survival) at 25 µM, surpassing free MB. Biofilm eradication studies using the crystal violet (CV) assay revealed 37.26% inhibition of Escherichia coli (E. coli) biofilm and 25.42% inhibition of Staphylococcus aureus (S. aureus) biofilm after 15 min of laser exposure compared to a nonirradiated control, indicating the potential for disrupting persistent infections. MB@ML-MOF50 is a promising multifunctional nanoplatform for targeted, pH-responsive, and enhanced photodynamic antibacterial therapy.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202500510"},"PeriodicalIF":3.4,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

New Structure Activity Relationship Insight into the Role of the C-3 Extension on Rifamycin Antimycobacterial Activity. 新结构-活性关系对利福霉素抗细菌活性的影响

IF 3.4 4区医学

ChemMedChem Pub Date : 2025-09-22 DOI: 10.1002/cmdc.202500673

Clinton G L Veale, Ewelina Smolarz, Aleksandra Leśniewska, Krystian Pyta, Piotr Przybylski

引用次数: 0

Benzoxazole-Acrylonitriles: Dual Bioactivity and DNA Binding from a Sustainable Synthetic Approach. 苯并恶唑-丙烯腈：可持续合成方法的双重生物活性和DNA结合。

IF 3.4 4区医学

ChemMedChem Pub Date : 2025-09-22 DOI: 10.1002/cmdc.202500429

Marina Galić, Tamara Rohtek, Leentje Persoons, Dirk Daelemans, Mihailo Banjanac, Tea Bruketa, Marijana Radić Stojković, Marijana Hranjec

{"title":"Benzoxazole-Acrylonitriles: Dual Bioactivity and DNA Binding from a Sustainable Synthetic Approach.","authors":"Marina Galić, Tamara Rohtek, Leentje Persoons, Dirk Daelemans, Mihailo Banjanac, Tea Bruketa, Marijana Radić Stojković, Marijana Hranjec","doi":"10.1002/cmdc.202500429","DOIUrl":"https://doi.org/10.1002/cmdc.202500429","url":null,"abstract":"Efficient synthesis in aqueous media is employed to prepare targeted compounds to evaluate antiproliferative, antibacterial, and antiviral activity in vitro. The biological activity is influenced by the type and number of substituents placed at phenyl or benzoxazole ring. Acrylonitriles substituted with 3,4-dihydroxy 50, 51, 3,4,5-tryhidroxy 52, 53, and 4-N,N-diethyl-amino 55 groups demonstrate potent antiproliferative effects against cancer cell lines, with IC50 values from 0.7 to 5.8 μM. Their impact on normal cell viability is assessed. The most active benzoxazoles induce DNA damage and are analyzed for their interaction with ct-DNA. UV/Vis titrations, thermal melting assays, and circular dichroism suggest an intercalative mode for the 4-N,N-diethylamino 55 and partial intercalation for the 3,4-dihydroxy 50 and 3,4,5-tryhidroxy derivative 52. Derivative 55 induces apoptosis and cell cycle arrest in cancer cells. Among tested benzoxazoles, significant antiviral activity against HCoV OC43 is observed for the 2-naphthyl 32, 3-indolyl 41 and 42 and p-hydroxy derivative 48 (EC50 from 2.1 to 8.5 μM). Furthermore, antibacterial activity is most effective for the 3,4-dihydroxy and bromine substituted acrylonitrile 51 against S. aureus (MIC 8 μM) and the efflux pump-deleted mutant of E. coli (MIC 4 μM), which is also observed for the hydroxy and bromine substituted 49.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202500429"},"PeriodicalIF":3.4,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synthesis of Caerulomycins E and A Analogs for Studying Cytotoxic Activity. 绿霉素E和A类似物的合成及其细胞毒活性研究。

IF 3.4 4区医学

ChemMedChem Pub Date : 2025-09-22 DOI: 10.1002/cmdc.202500594

Pansachon Intamalee, Jesada Maneewong, Natthiya Saehlim, Patamawadee Silalai, Arthit Chairoungdua, Rungnapha Saeeng

{"title":"Synthesis of Caerulomycins E and A Analogs for Studying Cytotoxic Activity.","authors":"Pansachon Intamalee, Jesada Maneewong, Natthiya Saehlim, Patamawadee Silalai, Arthit Chairoungdua, Rungnapha Saeeng","doi":"10.1002/cmdc.202500594","DOIUrl":"https://doi.org/10.1002/cmdc.202500594","url":null,"abstract":"Caerulomycin A, a marine-derived natural product featuring a bipyridinic core and a substituted oxime functional group, was originally isolated from Streptomyces caeruleus and is known for its antibiotic, antifungal, and cytotoxic properties. In this study, we report the efficient synthesis of caerulomycin A and a series of novel analogs via a five-step synthetic route using readily available reagents. The structural diversification focused on the replacing the methoxy group with various benzyl ether substituents at C-4 and subsequent oxidation and condensation steps at C-6 to generate caerulomycin E and caerulomycin A analogs. These compounds were evaluated for their cytotoxic activity against six human cancer cell lines. Notably, several benzyl ether derivatives exhibited significantly enhanced cytotoxicity compared to the parent compound, with some analogs demonstrating greater potency than the reference drug ellipticine. The structure-activity relationship (SAR) analysis revealed that halogenated substituted benzyl ether groups at C-4 positions played a critical role in modulating cytotoxic activity and selectivity. These findings underscore the potential of synthetic caerulomycin derivatives as promising lead compounds for further development in cancer therapeutics.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202500594"},"PeriodicalIF":3.4,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145123846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

5-Amino-7-Oxo-4,7-Dihydroazolo[1,5-a]pyrimidine-6-Carbonitriles: Synthesis and Study of Antitumor Effect In Vitro and In Silico. 5-氨基-7-氧-4,7-二氢偶氮[1,5-a]嘧啶-6-碳腈的合成及体外和硅内抗肿瘤作用研究

IF 3.4 4区医学

ChemMedChem Pub Date : 2025-09-21 DOI: 10.1002/cmdc.202500535

Veronika V Dolgova, Konstantin V Savateev, Grigoriy V Urakov, Evgeniya T Shabunina, Tatiana E Sbrodova, Ekaterina A Lvova, Ilya I Butorin, Elena A Fesenko, Vsevolod V Melekhin, Maria D Tokhtueva, Anastasiya V Paramonova, Andrey A Zonov, Svetlana K Kotovskaya, Vladimir L Rusinov

{"title":"5-Amino-7-Oxo-4,7-Dihydroazolo[1,5-a]pyrimidine-6-Carbonitriles: Synthesis and Study of Antitumor Effect In Vitro and In Silico.","authors":"Veronika V Dolgova, Konstantin V Savateev, Grigoriy V Urakov, Evgeniya T Shabunina, Tatiana E Sbrodova, Ekaterina A Lvova, Ilya I Butorin, Elena A Fesenko, Vsevolod V Melekhin, Maria D Tokhtueva, Anastasiya V Paramonova, Andrey A Zonov, Svetlana K Kotovskaya, Vladimir L Rusinov","doi":"10.1002/cmdc.202500535","DOIUrl":"https://doi.org/10.1002/cmdc.202500535","url":null,"abstract":"A novel chemotype of nitrile-containing azolopyrimidines with potential antitumor activity has been proposed, and a method for the synthesis of the corresponding 5-amino-7-oxoazolo[1,5-a]pyrimidine-6-carbonitriles by cyclocondensation of various aminoazoles and ethyl 2-cyano-3-R-amino-3-(methylsulfanyl)acrylates has been developed. Cytotoxic effects of the obtained azolopyrimidines against glioblastoma (A-172), bladder carcinoma (T-24), lung carcinoma (A-549), and human embryonic kidney (HEK-293) cells have been investigated, and structure-activity relationships have been identified. 2-Phenyl-5-(morpholin-4-yl)-7-oxo-1,2,4-triazolo[1,5-a]pyrimidine-6-carbonitrile 5j has been found to exhibit selective cytotoxic activity against the T-24 cells (IC50 = 14.68 µM), whereas 3-bromo-5-(morpholin-4-yl)-7-oxopyrazolo[1,5-a]pyrimidine-6-carbonitrile 5v has shown selective toxicity against the A-172 cells (IC50 = 18.38 µM). Further studies on heterocycle 5j in the annexin V apoptosis assay indicate that the primary mechanism involves inhibition of proliferative activity rather than induction of cell death. The cyclin-dependent kinase 2 protein is suggested as a possible target for the cytotoxic action of the studied compounds 5 on the T-24 cell line according to the notable correlation between docking studies and MTT assay results.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202500535"},"PeriodicalIF":3.4,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

AgamOBP1-Directed Discovery of Repellents to Control the Spread of Mosquito-Borne Diseases. 以agamobp1为导向的驱蚊剂的发现以控制蚊媒疾病的传播。

IF 3.4 4区医学

ChemMedChem Pub Date : 2025-09-21 DOI: 10.1002/cmdc.202500555

Evanthia Chazapi, Eftichia Kritsi, Constantinos Potamitis, Panagiota G V Liggri, Katerina E Tsitsanou, Christina E Drakou, Antonios Michaelakis, Dimitrios P Papachristos, Spyros E Zographos, Maria Zervou, Theodora Calogeropoulou

{"title":"AgamOBP1-Directed Discovery of Repellents to Control the Spread of Mosquito-Borne Diseases.","authors":"Evanthia Chazapi, Eftichia Kritsi, Constantinos Potamitis, Panagiota G V Liggri, Katerina E Tsitsanou, Christina E Drakou, Antonios Michaelakis, Dimitrios P Papachristos, Spyros E Zographos, Maria Zervou, Theodora Calogeropoulou","doi":"10.1002/cmdc.202500555","DOIUrl":"https://doi.org/10.1002/cmdc.202500555","url":null,"abstract":"Toward the discovery of novel efficient repellents, protein-directed dynamic combinatorial chemistry (pdDCC) coupled to saturation-transfer difference (STD) NMR spectroscopy was initially employed to identify modulators of the malaria vector Anopheles gambiae Odorant Binding Protein 1 (AgamOBP1). A library of potential binders of AgamOBP1 (secondary amines) generated from two amines and seven aldehydes was designed aiming to enable interactions with critical amino acids at the DEET-site and to bridge the DEET- and Icaridin sIC-binding pockets, both implicated in repellents recognition. Solubility issues hindered the clear identification of binders among the DCL members, except for one sublibrary, leading us to shift our strategy towards the synthesis of the designed amines, followed by direct evaluation of their binding to AgamOBP1 using 1H STD NMR spectroscopy. The identified binders were further validated in vitro by fluorescence competition assays, and the most potent compounds which also possessed suitable vapor pressure were evaluated as repellents in arm-in-cage behavioral assays against Aedes albopictus. Amines 2A, 3A, 4A, and 6A showed significant repellent activity. The most potent was compound 4A (4-methyl-N-(pyridin-4-ylmethyl)aniline) which acted as a a DEET-like repellent at 0.4 μL cm- 2 dose. Thus, our strategy showcased a promising scaffold for further optimization toward efficient mosquito repellents.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202500555"},"PeriodicalIF":3.4,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Front Cover: Development of Carborane-Based Halogenated Naphthyridinone-Analogues as Cannabinoid Receptor Type 2 (CB2R) Ligands (ChemMedChem 17/2025) 封面：碳硼烷基卤化萘嘧啶类似物作为大麻素受体2型（CB2R）配体的发展（ChemMedChem 17/2025）

IF 3.4 4区医学

ChemMedChem Pub Date : 2025-09-18 DOI: 10.1002/cmdc.70021

Lea Ueberham, Winnie Deuther-Conrad, Peter Lönnecke, Aleksandr Kazimir, Evamarie Hey-Hawkins

引用次数: 0

Next-Generation Bcl-2 Inhibitors: Design and Evaluation of Indolyl-Triazole Derivatives with Anticancer Potential. 下一代Bcl-2抑制剂：具有抗癌潜力的吲哚-三唑衍生物的设计和评价。

IF 3.4 4区医学

ChemMedChem Pub Date : 2025-09-18 DOI: 10.1002/cmdc.202500265

Ahmed M Almehdi, Samar Damiati, Ihsan A Shehadi, Mohamed El-Sadek, Arwyn T Jones, Abdalla El-Kabalawy, Yasmina Lashine, Yogendra Nayak, Sameh S M Soliman, Andrew D Westwell, Rania Hamdy

{"title":"Next-Generation Bcl-2 Inhibitors: Design and Evaluation of Indolyl-Triazole Derivatives with Anticancer Potential.","authors":"Ahmed M Almehdi, Samar Damiati, Ihsan A Shehadi, Mohamed El-Sadek, Arwyn T Jones, Abdalla El-Kabalawy, Yasmina Lashine, Yogendra Nayak, Sameh S M Soliman, Andrew D Westwell, Rania Hamdy","doi":"10.1002/cmdc.202500265","DOIUrl":"https://doi.org/10.1002/cmdc.202500265","url":null,"abstract":"The Bcl-2 protein family plays a critical role in regulating apoptosis, making it a key target for cancer therapy. In this study, a series of novel Bcl-2 inhibitors have been designed, synthesized, and evaluated. To disrupt the interactions between anti-apoptotic Bcl-2 and pro-apoptotic proteins, compounds were developed based on essential pharmacophoric features. Among the tested compounds, R4, R14, R17, and R23 demonstrated potent anticancer activity with sub-micromolar IC50 concentrations across various Bcl-2 expressing human cancer cell lines (IC50 ranges: 1.46-7.67 µM for cancer cells). ELISA binding assays further validated the efficacy of R4, R14, and R23, showcasing their potency with IC50 values ranging from 0.25 to 0.63 µM, compared to gossypol and ABT-199 (venetoclax), with IC50 values of 0.6 and 0.038 µM, respectively. Furthermore, the R23 revealed a significant induction of late and early apoptosis and cell cycle arrest at G1 phase. Noteworthy, R23 emerged as a promising candidate with unique computational analysis, showing superior displacement of hydration sites and higher ΔG values in WaterMap studies. Moreover, molecular dynamics simulations reveal low root mean square deviation fluctuations, indicating strong and stable interactions with Bcl-2. These findings underscore the therapeutic potential of R23 as a Bcl-2 inhibitor.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202500265"},"PeriodicalIF":3.4,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Letting Go of Pains and Other Dogmas 放下痛苦和其他教条。

IF 3.4 4区医学

ChemMedChem Pub Date : 2025-09-18 DOI: 10.1002/cmdc.202500199

Christina L. L. Chai

引用次数: 0

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