Ilaria Chiocchio, Antonio De Agostini, Manuela Mandrone, Pierluigi Cortis, Clarissa Tarozzi, Ferruccio Poli, Cinzia Sanna
{"title":"Chemoprofiling of Himantoglossum robertianum (Loisel.) P. Delforge leaves reveals predominance of gastrodigenin and structurally related compounds.","authors":"Ilaria Chiocchio, Antonio De Agostini, Manuela Mandrone, Pierluigi Cortis, Clarissa Tarozzi, Ferruccio Poli, Cinzia Sanna","doi":"10.1007/s13659-025-00526-7","DOIUrl":"https://doi.org/10.1007/s13659-025-00526-7","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to phytochemically profile Himantoglossum robertianum leaves. In fact, despite its wide distribution and its use in traditional medicine, this orchid is still understudied and little is known about its phytochemicals.</p><p><strong>Methods: </strong>The analyses were performed by <sup>1</sup>H NMR fingerprinting, elucidated by further 2D NMR and UHPLC-MS experiments. Both primary and secondary metabolites were qualified and quantified. The study was carried out comparing six natural populations by metabolomics approach, allowing further considerations on the influence of the environment on the concentration of metabolites.</p><p><strong>Results: </strong>This work brings to light a surprising phytochemical parallel between H. robertianum and the medicinal orchid Gastrodia elata. In fact, the most abundant specialized metabolites resulted: gastrodigenin, gastrodin, bis(4-hydroxybenzyl)ether, parishin A, parishin C, and parishin E. Interestingly, these metabolites are all known for their potential in the treatment of neurological disorders and are, indeed, the active principles of Gastrodia elata, an important orchid used in Traditional Chinese Medicine. The active metabolites were present in all the natural populations, where only slight variations in their concentration were revealed.</p><p><strong>Conclusion: </strong>Mapping the metabolome of H. robertianum leaves has provided new insights into the study of orchids, including diagnostic signals for rapid identification of gastrodigenin-like compounds directly from the <sup>1</sup>H NMR profile of a crude extract. From a bioprospecting perspective, finding active metabolites in leaves makes the plant source more valuable than the perennial hypogeal organs that are usually the herbal drug of orchids (i.e. G. elata).</p>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"15 1","pages":"45"},"PeriodicalIF":4.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Unlocking potent anti-tuberculosis natural products through structure-activity relationship analysis.","authors":"Delfly Booby Abdjul, Fitri Budiyanto, Joko Tri Wibowo, Tutik Murniasih, Siti Irma Rahmawati, Dwi Wahyu Indriani, Masteria Yunovilsa Putra, Asep Bayu","doi":"10.1007/s13659-025-00529-4","DOIUrl":"10.1007/s13659-025-00529-4","url":null,"abstract":"<p><p>Tuberculosis (TB) remains a world health problem due to the high number of affected individuals, high mortality rates, prolonged treatment durations, and the increasing prevalence of resistance to commercial TB drugs. The emergence of resistance to anti-TB drugs has necessitated urgent research into drug discovery and development, focusing on novel mechanisms of action against Mycobacterium tuberculosis resistant strains. Natural products, with their remarkable structural diversity and bioactivity, are promising sources for the development of new TB drugs or the identification of potential chemical scaffolds exhibiting potent and novel biological activity with minimal or no cytotoxicity to host cells. This review focuses on potent anti-TB natural products with minimum inhibitory concentration (MIC) values below 5 µg mL<sup>-1</sup> and examines their structure-activity relationship (SAR). Significant characteristics and relevant biological properties of each compound were analysed using a Random Forest, machine learning algorithm, to explore SAR. Using molecular docking, AutoDock Vina was utilised to assess molecular interactions with protein targets, and predictive accuracy was enhanced using the XGBoost machine learning model. These analyses provide insights into the mode of action of these compounds and help identify key structural features contributing to their anti-TB activity. In addition, this review examines the correlation between the potency of selected anti-TB compounds and their cytotoxicity, offering valuable insights for the identification of promising scaffolds in TB drug discovery.</p>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"15 1","pages":"44"},"PeriodicalIF":4.8,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12234934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Exploring the antineoplastic potential of α-mangostin in breast cancer.","authors":"Daniela Amador-Martínez, Mizraim Flores, Rafael Vargas-Castro, Rocío García-Becerra, Euclides Avila, Lorenza Díaz, Janice García-Quiroz","doi":"10.1007/s13659-025-00528-5","DOIUrl":"10.1007/s13659-025-00528-5","url":null,"abstract":"<p><p>Among women, breast cancer is the most frequently diagnosed cancer and the leading cause of cancer-related mortality globally. Despite improvements in early detection and diagnosis, some risk factors have been on the rise, including the decline in birth rate, the use of oral contraceptives, and the escalation in alcohol consumption and obesity. Thus, there is an imperative urgent need to expand accessible prevention and treatment options for breast cancer. Regarding these tumors, several natural compounds have shown efficacy in slowing or preventing their progression, offering a promising therapeutic alternative. Among these, α-mangostin, a xanthone derived from mangosteen, has demonstrated promising antitumor effects against different malignancies, particularly breast cancer. The mechanisms involved in α-mangostin´s therapeutic effects include downregulation of oncogenic ion channels, modulation of cell cycle progression, suppression of oncogene expression, and interference with steroid and growth factor receptors signaling. This review thoroughly explores these mechanisms, as well as updates information on α-mangostin chemical structure and its potential as a coadjuvant to conventional breast cancer therapies. Furthermore, we provide scientifically supported insights for the development of clinically applicable α-mangostin-based treatments, highlighting the robust body of evidence supporting its cancer-fighting properties, despite the absence of clinical studies to date.</p>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"15 1","pages":"43"},"PeriodicalIF":4.8,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12229438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ernest Oppong-Danquah, Jana Heumann, Hannah Moosbauer, Martina Blümel, Arlette Wenzel-Storjohann, Deniz Tasdemir
{"title":"Bioprospecting cultivable bacteria associated with deep sea (mesopelagic) fish of the North Atlantic Ocean.","authors":"Ernest Oppong-Danquah, Jana Heumann, Hannah Moosbauer, Martina Blümel, Arlette Wenzel-Storjohann, Deniz Tasdemir","doi":"10.1007/s13659-025-00527-6","DOIUrl":"10.1007/s13659-025-00527-6","url":null,"abstract":"<p><p>The microbiota associated with fish is increasingly recognized as a valuable source of bioactive metabolites for pharmaceutical application. The mesopelagic zone, a deep and unique ecosystem with a diverse biological community, is among the least studied marine environments. This study explored the potential of cultivable microbiota associated mainly with mesopelagic fish for pharmaceutical and agricultural applications. We isolated and identified 643 cultivable bacteria predominantly from various organs of fish collected from the mesopelagic zone of the North Atlantic Ocean, with additional samples from jellyfish, squid and krill. The bacterial community was dominated by the Gram-negative phylum Pseudomonadota, particularly the genera Psychrobacter, Pseudoalteromonas and Vibrio. A total of 394 bacterial isolates were selected and cultured in two growth media. Microbial extracts (590) were assessed for their anticancer and antimicrobial activities against human and fish pathogens. Over 60% of extracts exhibited activity against two ESKAPE pathogens methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecium, as well as the fish pathogen Lactococcus garvieae, highlighting their antimicrobial potential. We used an LC-MS/MS-based computational untargeted metabolomics and cutting-edge cheminformatics tools as well as manual dereplication strategies to chemically profile 26 most active extracts, and annotated compound classes such as bile acids, diketopiperazines, indole alkaloids and lipids. Many peak ions remained unannotated, suggesting the presence of new bioactive molecular families. These findings highlight the bioprospecting potential of cultivable bacteria associated with mesopelagic fauna.</p>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"15 1","pages":"42"},"PeriodicalIF":4.8,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12222571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Review on NMR spectroscopic data and recent analytical methods of aristolochic acids and derivatives in Aristolochia herbs.","authors":"Phan Minh Giang, Nguyen Nghia Vu, Vu Thanh Loc, Dong Ngoc Phuc, Ngiem Duc Trong, To Phuong Linh, Tran Thi Thu Thuy","doi":"10.1007/s13659-025-00506-x","DOIUrl":"10.1007/s13659-025-00506-x","url":null,"abstract":"<p><p>Aristolochic acids (AAs) are an important group of secondary metabolites in the genus Aristolochia. The presence of aristolochic acids infers the potency of many Aristolochia herbs used for ages in traditional medicine of China, Europe, Central America, India, and some other countries. Although being moderately cytotoxic, intake of AAs is associated with serious health problems, such as nephrotoxicity and carcinogenicity. Analyzing AAs in Aristolochia herbs is crucial for regulating their efficacy and toxicity because phytochemistry works have shown the occurrence of AAs in almost all Aristolochia herbs studied. Using two-dimensional parameters, chemical shifts and coupling constants, NMR spectroscopy is a modern, accurate, and reliable method in the analysis of secondary metabolites. Comparing experimental spectroscopic data with those of known and related compounds helps simplify the structural identification of secondary metabolites. The compilation of an NMR database of AAs from scattered sources would also be useful in NMR-based metabolomics. The present review provides updated information on sources and NMR spectroscopic data of 54 aristolochic acid derivatives, including AAs and their methyl esters, denitroaristolochic acids and their derivatives, and sesqui- and diterpene esters of AAs. The report also covers the newest development of analytical and preparative methods used in separation, identification, and quantification of AAs in Aristolochia herbal samples.</p>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"15 1","pages":"41"},"PeriodicalIF":4.8,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Discovery of structurally diverse polyprenylated acylphloroglucinols with quorum sensing inhibitory activity from Hypericum seniawinii Maxim.","authors":"Yulin Duan, Xiaoxia Gu, Xincai Hao, Guosheng Cao, Weiguang Sun, Changxing Qi, Yonghui Zhang","doi":"10.1007/s13659-025-00520-z","DOIUrl":"10.1007/s13659-025-00520-z","url":null,"abstract":"<p><p>Four previously undescribed polyprenylated acylphloroglucinols, hyperisenins A-D (1-4), along with two known analogues (5 and 6), were obtained from the aerial part of Hypericum seniawinii Maxim. Compounds 1 and 2 were two highly degraded polyprenylated acylphloroglucinols with a cyclohexanone-monocyclic skeleton, while compound 3 was the first example of O-prenylated acylphloroglucinols with a 6/6/6 ring system. Their structures were identified by analyzing NMR, HRESIMS data, and quantum chemical calculations. The biosynthetic pathway of 1 and 2 might originate from bicyclic polyprenylated acylphloroglucinols via a series of complex retro-Claisen, keto - enol tautomerism, and intramolecular cyclization. The bioassay results showed that 4 exhibited quorum sensing inhibitory activity against Pseudomonas aeruginosa, which could decrease the activation of the rhl system, and significantly reduce rhamnolipid levels at a concentration of 100 µM, and the mechanism might be the ability to bind 4 to lasR and pqsR.</p>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"15 1","pages":"40"},"PeriodicalIF":4.8,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Exploring anti-SARS-CoV-2 natural products: dual-viral target inhibition by delphinidin and the anti-coronaviral efficacy of deapio platycodin D.","authors":"Jiani Lu, Yan Tang, Hongtao Li, Saisai Tian, Xixiang Chen, Xueyue Song, Pengcheng Qin, Jianrong Xu, Haiyan Zhu, Liqiang Ni, Huarong Du, Weidong Zhang, Weihua Li, Lili Chen","doi":"10.1007/s13659-025-00523-w","DOIUrl":"10.1007/s13659-025-00523-w","url":null,"abstract":"<p><p>Qingfei Paidu decoction (QFPDD) has been extensively used in clinical treatments during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic. SARS-CoV-2 primarily invades host cells via its spike (S) protein binding to the angiotensin-converting enzyme 2 (ACE2) on the cell membrane, mediating viral-host membrane fusion. Blocking viral entry is a crucial step in preventing infection, with the interaction between the S receptor binding domain (S-RBD) and ACE2 being a key antiviral target. Given that SARS-CoV-2 predominantly affects the respiratory system and approximately 25% of patients suffering from corona virus disease 2019 (COVID-19) with gastrointestinal symptoms, we are committed to identifying more active ingredients in QFPDD that target the respiratory and gastrointestinal tracts of COVID-19 patients. Among medicinal plants, ephedra and liquorice derived from QFPDD, along with two other Chinese herbs, Platycodon grandiflorum and Radix Rhei Et Rhizome (rhubarb), have garnered our interest. These herbs have historically been used in traditional Chinese medicine (TCM) for treating infectious diseases with respiratory and digestive symptoms. Here, we established a library containing all components of the four individual herbs gathered from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and performed structure-based virtual screening to identify potential ACE2/S-RBD inhibitors. Subsequently, we selected 10 ingredients from the top 30 candidates and evaluated their activities using a pseudovirus neutralization assay. Delphinidin and deapio platycodin D (DPD) showed significant antiviral potential with half-maximal inhibitory concentration (IC<sub>50</sub>) values of 45.35 µM and 1.38 µM, respectively. Furthermore, delphinidin also inhibited the 3-chymotrypsin-like protease (3CL<sup>pro</sup>), indicating its dual-viral target inhibitory potential. Notably, DPD effectively suppressed HCoV-229E replication in BEL-7402 cells. This study not only provides a strategy for rapid identifying antiviral agents from TCM in anticipation of future pandemics but also offers theoretical and experimental evidence to support for the clinical use of QFPDD.</p>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"15 1","pages":"39"},"PeriodicalIF":4.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12165925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144281943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Design of 20-deoxyingenol-esters-based PKC agonists and their lysosome biogenesis-enhancing activity.","authors":"Jia-Jia Wan, Qiu-Yuan Yin, Mao Sun, Cui-Shan Zhang, Hao-Jing Zang, Pei-Tong Yao, Ming-Rui Yuan, Ding-Kang Chen, Feng Guo, Qun Chen, Bo-Wen Ouyang, Zi-Fei Xu, Ming-Ming Cao, Chong-Lin Yang, Xiao-Jiang Hao, Ying-Tong Di","doi":"10.1007/s13659-025-00522-x","DOIUrl":"10.1007/s13659-025-00522-x","url":null,"abstract":"<p><p>The activation of conventional (α) and novel (δ) protein kinase C (PKC) isoforms promotes lysosomal biogenesis, a critical process for clearance of pathogenic protein aggregates including β-amyloid (Aβ) and phosphorylated Tau (p-Tau) in neurodegenerative disorders. Notably, PKC activators HEP14/15, characterized by 20-methyl moiety, fail to establish classical C1B domain pharmacophore interactions, suggesting a non-canonical activation mechanism. In this study, structural diversification of 20-deoxyingenol through esterification and acetonide protection yielded 18 new derivatives (2-19). Systematic screening revealed their lysosome-promoting activities, with structure-activity relationship analysis identifying compounds 4 and 18 as superior autophagy inducers. At 20 μM, these derivatives enhanced autophagic flux by 2.45-fold and 2.31-fold versus vehicle control. Moreover, compounds 4 and 18 exhibited a dose-dependent increase in lysosome numbers, promoted TFEB nuclear translocation, and enhanced lysosome-mediated lipid droplet clearance. Western blot analysis further revealed that compounds 4/18 upregulated proteins associated with the autophagy-lysosome system, suggesting their potential as promising autophagy inducers. Mechanistically, molecular docking simulations indicated thier high-affinity binding to PKCδ, which may explain their autophagy-enhancing properties.</p>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"15 1","pages":"38"},"PeriodicalIF":4.8,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chuan-Su Liu, Bing-Chao Yan, Han-Dong Sun, Jin-Cai Lu, Pema-Tenzin Puno
{"title":"Bridging chemical space and biological efficacy: advances and challenges in applying generative models in structural modification of natural products.","authors":"Chuan-Su Liu, Bing-Chao Yan, Han-Dong Sun, Jin-Cai Lu, Pema-Tenzin Puno","doi":"10.1007/s13659-025-00521-y","DOIUrl":"10.1007/s13659-025-00521-y","url":null,"abstract":"<p><p>Natural products (NPs) are invaluable resources for drug discovery, characterized by their intricate scaffolds and diverse bioactivities. AI drug discovery & design (AIDD) has emerged as a transformative approach for the rational structural modification of NPs. This review examines a variety of molecular generation models since 2020, focusing on their potential applications in two primary scenarios of NPs structure modification: modifications when the target is identified and when it remains unidentified. Most of the molecular generative models discussed herein are open-source, and their applicability across different domains and technical feasibility have been evaluated. This evaluation was accomplished by integrating a limited number of research cases and successful practices observed in the molecular optimization of synthetic compounds. Furthermore, the challenges and prospects of employing molecular generation modeling for the structural modification of NPs are discussed.</p>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"15 1","pages":"37"},"PeriodicalIF":4.8,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12144013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144232912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cristina Gan, Elisa Langa, Gang Wang, Françoise Van Bambeke, Diego Ballestero, María Rosa Pino-Otín
{"title":"Mechanisms of action and resistance prevention of synergistic thymol and carvacrol combinations with antibiotics in Staphylococcus aureus and Acinetobacter baumannii.","authors":"Cristina Gan, Elisa Langa, Gang Wang, Françoise Van Bambeke, Diego Ballestero, María Rosa Pino-Otín","doi":"10.1007/s13659-025-00518-7","DOIUrl":"10.1007/s13659-025-00518-7","url":null,"abstract":"<p><p>The use of natural products as antibiotic adjuvants to enhance efficacy and mitigate resistance is increasingly recognized as a promising strategy. This study explored five novel synergistic antimicrobial combinations (SACs) of carvacrol (CARV) and three already identified SACs of thymol (THY) with chloramphenicol, gentamicin, and streptomycin against Staphylococcus aureus and Acinetobacter baumannii, critical WHO-listed pathogens, and investigated their mechanisms of action and resistance-prevention capabilities. Despite being isomers, CARV and THY exhibited distinct synergistic effects and fractional inhibitory concentration index (FICI) values depending on the antibiotic and bacterial species. The SACs significantly reduced the required antibiotic dose by 4- to 16-fold, with FICI values ranging from 0.25 to 0.5. Growth kinetics revealed that SACs completely inhibited planktonic bacterial growth, outperforming antibiotics alone. Additionally, the SACs demonstrated efficacy in both inhibiting and eradicating biofilms of S. aureus and A. baumannii. Resistance development studies highlighted that neither THY nor CARV induced resistance in these pathogens. Moreover, SACs combining aminoglycosides with THY reduced the emergence of resistance in A. baumannii by up to 32-fold. In S. aureus, THY mitigated gentamicin resistance by 16-fold. CARV exhibited similar, albeit slightly less potent, effects.Mechanistic investigations revealed that THY and CARV exert antimicrobial action by multiple mechanisms, including bacterial membrane depolarization and disruption, efflux pump inhibition, disrupting ATP metabolism and mitigating oxidative stress induced by antibiotics. These findings highlight the potential of SACs to enhance antibiotic efficacy while preventing resistance, positioning them as strong candidates for innovative antimicrobial therapies against multidrug-resistant pathogens.</p>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"15 1","pages":"36"},"PeriodicalIF":4.8,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12144027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144232913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}