ChemMedChem最新文献_第5页

Schiff Base Derivatives of Benzothiazole and Benzamide as Promising Antimicrobial Agents: Integrated In Silico and In Vitro Evaluation 苯并噻唑和苯甲酰胺希夫碱衍生物有前景的抗菌药物：硅合成和体外评价

IF 3.5 4区医学

ChemMedChem Pub Date : 2026-09-13 DOI: 10.1002/cmdc.70499

Temitope A. Ogunnupebi, Gbolahan O. Oduselu, Oluwadunni F. Elebiju, Oluwabukayo T. Opebiyi, Natasha October, Olayinka O. Ajani, Ezekiel Adebiyi

{"title":"Schiff Base Derivatives of Benzothiazole and Benzamide as Promising Antimicrobial Agents: Integrated In Silico and In Vitro Evaluation","authors":"Temitope A. Ogunnupebi, Gbolahan O. Oduselu, Oluwadunni F. Elebiju, Oluwabukayo T. Opebiyi, Natasha October, Olayinka O. Ajani, Ezekiel Adebiyi","doi":"10.1002/cmdc.70499","DOIUrl":"https://doi.org/10.1002/cmdc.70499","url":null,"abstract":"Antimicrobial resistance (AMR) remains a critical global health challenge, demanding new scaffolds with potent and broad-spectrum activity. In this work, a library of Schiff-base derivatives of benzothiazoles (2a–2f) and benzamides (5a–5i) was designed, synthesised via a microwave-assisted approach, and comprehensively characterised by 1H-/13C-NMR, FT-IR, and UV–Vis spectroscopy. In silico ADMET profiling predicted favourable pharmacokinetics and low toxicity. Molecular docking of the compounds against E. coli glucosamine-6-phosphate synthase (2VF5) and C. albicans lanosterol 14α-demethylase (5V5Z) revealed strong binding affinities, surpassing ciprofloxacin and fluconazole. Compounds 5f and 2f (−8.1 and −8.0 kcal/mol) for 2VF5, while 2a and 5h had good binding affinity (−9.7 and −9.6 kcal/mol) for 5V5Z, showing optimal interactions with key catalytic residues, maintaining structural stability in molecular dynamics simulations. Consistent with these predictions, compounds 5h, 5f, and 2a exhibited potent antibacterial activity (MIC: 3.13–12.5 µg/mL) against both Gram-positive and Gram-negative strains, and antifungal activity (MIC: 6.25–12.5 µg/mL against C. albicans and A. fumigatus). Structure–activity relationship (SAR) analysis revealed that aryl substitution influenced bioactivity, with 4-ethoxy (5h), 2-hydroxy (5f), and 2-fluoro (2a) groups being active, whereas unsubstituted analogues were inactive. These compounds are highlighted as promising antimicrobial leads requiring further in vivo evaluation.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"21 18","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148950559","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 and Evaluation of Peptoid-Based Compound Libraries as Inhibitors of Parasite Metallo-Aminopeptidases 寄生虫金属氨基肽酶抑制剂肽类化合物文库的合成与评价。

IF 3.5 4区医学

ChemMedChem Pub Date : 2026-09-10 DOI: 10.1002/cmdc.70433

Mirta Elisa Aguado, Gerardo M. Ojeda-Carralero, Mario Antonio Rodríguez, Isabella Rúa, Heisy Guerra, Edoardo Bailo Hernández, Guglielmo Coppola, Susana Alberti, Ariatne Rodríguez, Maikel Izquierdo, Christian Betzel, Filippo Pettazzi, Julieta Coro-Bermello, Erik V. Van der Eycken, Bernhard Westermann, Jorge González-Bacerio, Daniel G. Rivera

{"title":"Synthesis and Evaluation of Peptoid-Based Compound Libraries as Inhibitors of Parasite Metallo-Aminopeptidases","authors":"Mirta Elisa Aguado, Gerardo M. Ojeda-Carralero, Mario Antonio Rodríguez, Isabella Rúa, Heisy Guerra, Edoardo Bailo Hernández, Guglielmo Coppola, Susana Alberti, Ariatne Rodríguez, Maikel Izquierdo, Christian Betzel, Filippo Pettazzi, Julieta Coro-Bermello, Erik V. Van der Eycken, Bernhard Westermann, Jorge González-Bacerio, Daniel G. Rivera","doi":"10.1002/cmdc.70433","DOIUrl":"10.1002/cmdc.70433","url":null,"abstract":"Parasitic diseases are a worldwide health and socio-economical problem, especially due to increasing parasite resistance and frequent toxicity of commercial drugs. Parasite metallo-aminopeptidases are potential therapeutic targets, as they perform crucial biological functions during parasite development within the human host. Here, we describe the synthesis and biological evaluation of two libraries consisting of a total of 74 peptoid-based compounds. The synthetic approaches use a multicomponent reaction to install various diversity elements, and in library one, this is followed by subsequent coupling to α-amino acids to create further diversity within a peptoid-peptide hybrid skeleton. The libraries were evaluated against three metallo-aminopeptidases: PfA-M1 from Plasmodium falciparum, TcLAP from Trypanosoma cruzi, and LmLAP from Leishmania major, which allowed the discovery of moderate to potent inhibitors of each enzyme. Molecular docking studies were conducted to help understand the binding mode of the inhibitors with the enzymes, predicting the importance of hydrophobic interactions in the inhibition process.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"21 17","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cmdc.70433","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Phosphorylated Analogs of Paracetamol and Their Anti-Inflammatory Potential 对乙酰氨基酚的磷酸化类似物及其抗炎潜能。

IF 3.5 4区医学

ChemMedChem Pub Date : 2026-09-10 DOI: 10.1002/cmdc.70469

Osvaldo León de la Cruz, Gabriel Alfonso Gutiérrez-Rebolledo, Carlos Zepactonal Gómez Castro, Ángel Daniel Campos Juárez, Porfirio Alonso Ruiz-Hurtado, Josué Rodríguez-Lozada, José Luis Castrejón-Flores, María Guadalupe Ramírez-Sotelo, Marco Franco-Pérez, Angel Zamudio-Medina

{"title":"Phosphorylated Analogs of Paracetamol and Their Anti-Inflammatory Potential","authors":"Osvaldo León de la Cruz, Gabriel Alfonso Gutiérrez-Rebolledo, Carlos Zepactonal Gómez Castro, Ángel Daniel Campos Juárez, Porfirio Alonso Ruiz-Hurtado, Josué Rodríguez-Lozada, José Luis Castrejón-Flores, María Guadalupe Ramírez-Sotelo, Marco Franco-Pérez, Angel Zamudio-Medina","doi":"10.1002/cmdc.70469","DOIUrl":"10.1002/cmdc.70469","url":null,"abstract":"Paracetamol is a widely used analgesic and antipyretic agent; however, its use is limited by minimal anti-inflammatory activity and the risk of hepatotoxicity from prolonged oral use or in acute overdose. To address these limitations, four novel phosphorylated paracetamol analogs (2a–2d) were synthesized via a UV-radical methodology and evaluated through integrated in silico, in vitro, and in vivo for anti-inflammatory dermal approaches. Molecular docking suggested plausible binding interactions with COX-1 and COX-2 for all analogs. In vitro cytotoxicity assays in THP-1 cells showed that 2a and 2b did not affect cell viability at 100 μM over 24 h. In a TPA-induced acute ear edema model in CD1 male mice, 2a produced about 50% inhibition of edema at the lowest tested quantity (0.5 mg/ear), representing a fourfold potency advantage over indomethacin at the same amount, while 2b displayed significant anti-inflammatory and vasoregulatory activity at higher quantities. Computational ADME profiling indicated that all analogs satisfy Lipinski’s drug-likeness criteria and exhibit low predicted hERG channel risk. These results support N-phosphorylation of 4-aminophenol as a viable strategy to improve the topical anti-inflammatory efficacy of paracetamol analogs.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"21 17","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928543","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

Novel Steroidal (Thio)barbiturate Hybrids: From Design to Preclinical Assessment in Tumor Therapy 新型类固醇（硫代）巴比妥酸盐混合物：从设计到肿瘤治疗的临床前评估。

IF 3.5 4区医学

ChemMedChem Pub Date : 2026-09-10 DOI: 10.1002/cmdc.70476

Alexandra Varges, João Serrano, Paula Arias, Pedro Soeiro, Marla Machava, Inês Figueiredo, Eurico Lima, Gilberto Alves, Adriana Oliveira Santos, Renato Boto, Paulo Almeida, Samuel Silvestre, Mariana Matias

{"title":"Novel Steroidal (Thio)barbiturate Hybrids: From Design to Preclinical Assessment in Tumor Therapy","authors":"Alexandra Varges, João Serrano, Paula Arias, Pedro Soeiro, Marla Machava, Inês Figueiredo, Eurico Lima, Gilberto Alves, Adriana Oliveira Santos, Renato Boto, Paulo Almeida, Samuel Silvestre, Mariana Matias","doi":"10.1002/cmdc.70476","DOIUrl":"10.1002/cmdc.70476","url":null,"abstract":"Cancer remains a public health concern with high rates of incidence and mortality, despite the significant advances achieved in recent decades. Therefore, this study aimed to develop novel hybrid molecules with potential anticancer properties. To this end, a steroid nucleus, specifically pregnenolone or dehydroepiandrosterone (DHEA), was covalently linked to a (thio)barbiturate scaffold. The hybrid molecules showed relevant antiproliferative activity against breast (MCF-7) and prostate (PC-3) cancer cells (IC50 = 8.73–38.53 and 4.08–36.01 µM, respectively), with selectivity indices of up to 2.79. The most promising compounds 4b (pregnenolone–barbiturate hybrid) and 7f (DHEA–thiobarbiturate hybrid) induced cell cycle arrest in the G0/G1 phase of breast cancer cells, with the DHEA–thiobarbiturate hybrid demonstrating a 6.6- and a 2.0-fold increase in apoptotic cells compared with untreated cells and cells treated with the anticancer drug 5-fluourouracil, respectively. Interestingly, a docking study suggested that these new hybrids may exhibit significant affinity for CYP17 and 5α-reductase enzymes. Preliminary pharmacokinetic investigation of the most promising hybrids suggested low intestinal absorption, which may be improved through appropriate formulation strategies. Overall, these findings indicate that these novel hybrid compounds, incorporating both (thio)barbiturates and steroid nuclei, represent a promising strategy for the development of anticancer drug candidates.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"21 17","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928553","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 and Assessment of the Enantioselectivity in Antitumor Activity of a Library of Novel Chiral Flavone Derivatives 新型手性黄酮衍生物库的合成及抗肿瘤活性的对映体选择性评价。

IF 3.5 4区医学

ChemMedChem Pub Date : 2026-09-10 DOI: 10.1002/cmdc.70482

Cláudia Pinto, Flávia Barbosa, João Machado, Andrea Cunha, Patrícia M. A. Silva, Mariangela Agamennone, Hassan Bousbaa, Honorina Cidade, Odília Queirós, Maria Elizabeth Tiritan

{"title":"Synthesis and Assessment of the Enantioselectivity in Antitumor Activity of a Library of Novel Chiral Flavone Derivatives","authors":"Cláudia Pinto, Flávia Barbosa, João Machado, Andrea Cunha, Patrícia M. A. Silva, Mariangela Agamennone, Hassan Bousbaa, Honorina Cidade, Odília Queirós, Maria Elizabeth Tiritan","doi":"10.1002/cmdc.70482","DOIUrl":"10.1002/cmdc.70482","url":null,"abstract":"Nature represents a rich source of bioactive compounds, with flavones emerging as privileged scaffolds owing to their multiple biological activities. Their antitumor potential arises from their ability to modulate pathways implicated in cancer progression and multidrug resistance, but structural modifications are often required to improve their pharmacokinetic properties and target selectivity. Incorporating chiral moieties, such as amino acids, may improve their potency and selectivity. Herein, we report the stereoselective synthesis of 32 new chiral derivatives of flavones (CDFs) obtained by coupling four commercial flavones with the enantiomerically pure amino esters and amino acids of tryptophan and tyrosine. Overall, the amino ester derivatives showed greater antiproliferative activity than their parent flavones against four cancer cell lines. 6HF-DTrp (14) and 7HF-DTrp (18) demonstrated micromolar equipotent inhibition with IC50 <21 µM against all cell lines. Most CDFs preferentially affected cancer cells over nontumor HPAEpiC cells, particularly 7HF-DTrp (18), which displayed selectivity indices above 6. Metabolic assays exposed heterogeneous effects on glucose consumption and lactate production, suggesting that CDF-induced cytotoxicity depends on the metabolic flexibility of each tumor phenotype rather than a universal mechanism. Furthermore, in vitro and in silico studies suggest potential P-glycoprotein (P-gp) inhibitory activity for 6HF-DTrp (14) and 7HF-DTrp (18).","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"21 17","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928575","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

Piano-Stool Ru (II) Complexes as Modulators of Human Prion Protein PrP106–126 Aggregation 钢琴-凳子Ru （II）复合物作为人朊蛋白PrP106-126聚集的调节剂。

IF 3.5 4区医学

ChemMedChem Pub Date : 2026-09-09 DOI: 10.1002/cmdc.70480

Rahul Chauhan, Himanshi Kumawat, Sakshi Saini, Abhishek Panwar, Prashant Kukreti, Nandita Medda, Partha Roy, Kaushik Ghosh

{"title":"Piano-Stool Ru (II) Complexes as Modulators of Human Prion Protein PrP106–126 Aggregation","authors":"Rahul Chauhan, Himanshi Kumawat, Sakshi Saini, Abhishek Panwar, Prashant Kukreti, Nandita Medda, Partha Roy, Kaushik Ghosh","doi":"10.1002/cmdc.70480","DOIUrl":"10.1002/cmdc.70480","url":null,"abstract":"Prion diseases are neurodegenerative disorders caused by the accumulation of misfolded prion proteins, leading to neurotoxicity and neuronal death. Creutzfeldt-Jakob disease (CJD) in humans and Bovine spongiform encephalopathy (BSE) in animals are among the most prominent prion disorders. Therefore, the search for molecules that can serve as drugs for prion diseases has gained significant attention. In our study, we synthesised and characterised two piano-stool ruthenium complexes, RuBT and RuBI, based on benzazole-quinoline scaffolds. Molecular structures of RuBT and RuBI were determined by X-ray crystallography. The anti-aggregation effects of the complexes on PrP106–126 aggregation were studied through ThT assay, CD, TEM, and AFM. Seeded aggregation assays demonstrated their ability to modulate seed-induced fibril formation. The interaction between the complexes and PrP106–126 was analysed using molecular docking and UV–visible spectroscopy. Molecular docking analysis showed good binding affinity with the PrP106–126. To demonstrate bioavailability and transport, the DNA and HSA binding affinities of complexes were computed. The complexes exhibited neuroprotective effects in HT-22 cells by reducing damage induced by PrP106–126. They also showed anticancer activity on human neuroblastoma SH-SY5Y cells. These findings suggest that these complexes facilitate future studies on full-length prion proteins and advanced disease models.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"21 17","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148917632","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

Exploring the Anticancer Potential of Schiff Base Complexes: A Mini-Review 探索希夫碱配合物的抗癌潜力：综述。

IF 3.5 4区医学

ChemMedChem Pub Date : 2026-09-09 DOI: 10.1002/cmdc.70484

Atif Ahmad, Anam, Marcos V. Palmeira-Mello, Sabir Khan, José Clayston Melo Pereira

引用次数: 0

Substituent Effects of Heptamethine Cyanine Dyes on Drug Uptake in Patient-Derived Glioma Cells 七甲基氰胺染料对患者源性胶质瘤细胞药物摄取的取代作用。

IF 3.5 4区医学

ChemMedChem Pub Date : 2026-09-07 DOI: 10.1002/cmdc.70486

Carina J. Dumo, Peter J. Choi, Yuge Liu, Osaid Muhammad, Jason A. Correia, Mike Dragunow, Thomas I-H. Park, Jiney Jose

引用次数: 0

Structure-Guided Identification of GPR84 Ligand Candidates With Potential Immunomodulatory Activities 具有潜在免疫调节活性的GPR84配体候选体的结构导向鉴定。

IF 3.5 4区医学

ChemMedChem Pub Date : 2026-09-07 DOI: 10.1002/cmdc.70488

Ha-Anh Thi Pham, Anamaria Morales-Alvarez, Timothy Gilbertson, Hung Nguyen

{"title":"Structure-Guided Identification of GPR84 Ligand Candidates With Potential Immunomodulatory Activities","authors":"Ha-Anh Thi Pham, Anamaria Morales-Alvarez, Timothy Gilbertson, Hung Nguyen","doi":"10.1002/cmdc.70488","DOIUrl":"10.1002/cmdc.70488","url":null,"abstract":"GPR84, a medium-chain fatty acid (MCFA)-sensing G protein-coupled receptor, plays a significant role in immune regulation. Despite its therapeutic potential, structurally diverse and well-characterized chemical probes of GPR84 remain limited. In the current study, we developed a novel structure-guided and dual-route pipeline to explore and prioritize small-molecule scaffolds compatible with the GPR84 orthosteric pocket, with pharmacophore-based ZINC screening and LigBuilder-based de novo design, accompanied by molecular docking, ADME filtering, and molecular dynamics, followed by immunoregulatory activity validation. ZINC screening identified ZINC149375 (SC787) and ZINC76994316 (Z109), which were further evaluated by 500-ns molecular dynamics simulations. Additionally, LIG081 and LIG133 from the LigBuilder-derived series emerged as computationally prioritized de novo candidates with favorable and persistent predicted interactions within the GPR84 orthosteric pocket. These ZINC-derived compounds demonstrated potent immune cell-dependent immunomodulatory activities associated with GPR84 functional agonism. SC787 and Z109 promote proinflammatory signaling in macrophages while suppressing activation and effector cytokine production in activated CD8+ T cells. Collectively, this study identifies structurally prioritized GPR84 pocket-compatible scaffolds for future receptor-focused immunological activity validation and medicinal chemistry optimization.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"21 17","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148904733","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

Effects of Mono- and Dicapsaicinoid Functionalization on the Physicochemical Properties and Antimicrobial Photodynamic Activity of Protoporphyrin IX 单和辣椒素功能化对原卟啉IX理化性质和抗菌光动力活性的影响。

IF 3.5 4区医学

ChemMedChem Pub Date : 2026-09-07 DOI: 10.1002/cmdc.70475

Ieda Vieira da Cunha, Gabriel Guimarães Calefi, Nagela Bernadelli Sousa Silva, Júlia Gomes Teixeira, Marcos Eduardo Gomes do Carmo, Paula Derksen Macruz, Eduardo Jorge Pilau, Antônio Otávio de Toledo Patrocínio, Carlos Henrique Gomes Martins, Celso de Oliveira Rezende Júnior, Tayana Mazin Tsubone

{"title":"Effects of Mono- and Dicapsaicinoid Functionalization on the Physicochemical Properties and Antimicrobial Photodynamic Activity of Protoporphyrin IX","authors":"Ieda Vieira da Cunha, Gabriel Guimarães Calefi, Nagela Bernadelli Sousa Silva, Júlia Gomes Teixeira, Marcos Eduardo Gomes do Carmo, Paula Derksen Macruz, Eduardo Jorge Pilau, Antônio Otávio de Toledo Patrocínio, Carlos Henrique Gomes Martins, Celso de Oliveira Rezende Júnior, Tayana Mazin Tsubone","doi":"10.1002/cmdc.70475","DOIUrl":"10.1002/cmdc.70475","url":null,"abstract":"Antimicrobial photodynamic therapy (aPDT) is a promising alternative for combating multidrug-resistant bacteria and overcoming limitations of conventional antimicrobial treatments. To improve aPDT performance, two Protoporphyrin IX (PpIX) derivatives functionalized with one or two capsaicin fragments were synthesized and biologically evaluated. Their physicochemical, photophysical, and antimicrobial properties were assessed against susceptible and resistant Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) strains. Mono- and disubstituted capsaicinoid-functionalized derivatives were isolated in 17% and 40% yields, respectively. Structural modification induced minor photophysical changes compared to PpIX, including slightly reduced singlet oxygen generation and photostability. Aggregation studies revealed that PpIX-capsaicin 1 exhibited a lower tendency to aggregate, whereas PpIX-capsaicin 2 showed persistent aggregation with coexistence of H- and J-type species. A significant increase in lipophilicity (Log P) was observed only for PpIX-capsaicin 2. Photoinactivation assays demonstrated superior efficacy of PpIX-capsaicin 1 against S. aureus, achieving ~3-log reduction, while limited activity was observed against E. coli, likely due to its complex cell envelope. In contrast, PpIX-capsaicin 2 showed no significant photoactivity. Overall, these findings demonstrate that increased functionalization does not necessarily improve photodynamic performance, highlighting the importance of balanced lipophilicity and aggregation control in photosensitizer design.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"21 17","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13549795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148904776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0