Powdery mildew is a pervasive fungal disease causing significant economic losses globally. Continuous use of synthetic fungicides has led to environmental concerns and resistant fungal strains. This study explores marine-derived cephalostatins from the South African Natural Compounds Database as novel fungicidal agents for managing powdery mildew. Using molecular docking techniques, we investigated the interaction between selected cephalostatins and critical proteins involved in powdery mildew pathogenesis. Compounds were selected based on drug-likeness and bioactivity, adhering to Lipinski's Rule of Five. Molecular interactions, binding affinities, and stability were analysed using AutoDock Vina, PyMOL, and Discovery Studio. Cephalostatin 17 exhibited the highest binding affinity (-10.4 kcal/mol), indicating strong potential for inhibiting fungal growth through significant hydrogen bonding and hydrophobic interactions. The study's primary limitation is the reliance on computational predictions, necessitating experimental validation. Cephalostatin 17 stands out as a promising candidate for sustainable agricultural practices.
{"title":"Exploring marine compounds as potential biocontrol agents against powdery mildew for agricultural sustainability: a computer-based approach.","authors":"Gokul Sudhakaran, Xinghui Liu, Bader O Almutairi, Moovendhan Meivelu, Kuppusamy Sathishkumar","doi":"10.1080/14786419.2024.2409985","DOIUrl":"https://doi.org/10.1080/14786419.2024.2409985","url":null,"abstract":"<p><p>Powdery mildew is a pervasive fungal disease causing significant economic losses globally. Continuous use of synthetic fungicides has led to environmental concerns and resistant fungal strains. This study explores marine-derived cephalostatins from the South African Natural Compounds Database as novel fungicidal agents for managing powdery mildew. Using molecular docking techniques, we investigated the interaction between selected cephalostatins and critical proteins involved in powdery mildew pathogenesis. Compounds were selected based on drug-likeness and bioactivity, adhering to Lipinski's Rule of Five. Molecular interactions, binding affinities, and stability were analysed using AutoDock Vina, PyMOL, and Discovery Studio. Cephalostatin 17 exhibited the highest binding affinity (-10.4 kcal/mol), indicating strong potential for inhibiting fungal growth through significant hydrogen bonding and hydrophobic interactions. The study's primary limitation is the reliance on computational predictions, necessitating experimental validation. Cephalostatin 17 stands out as a promising candidate for sustainable agricultural practices.</p>","PeriodicalId":18990,"journal":{"name":"Natural Product Research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372355","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}
Pub Date : 2024-10-04DOI: 10.1080/14786419.2024.2412305
Xin Liu, Mingzhu Ma, Yura Ha, Nan Wang, Yufang Zhou, Zhizhen Zhang
Four previously undescribed compounds talaromyester A (1) and purpuresters C-E (2-4), together with known purpurester A (5) and purpuride G (6), were isolated from the metabolites produced by the Mariana Trench sediment-derived fungus Talaromyces sp. SY2250. Compounds 2-5, two pairs of racemates, were separated on a chiral HPLC column. Structures of the isolated compounds were determined based on their HRESIMS data, extensive NMR spectroscopic analyses, and optical rotation calculations. Purpuride G (6) showed antiproliferative activity against glioma cells and may be the main active compound responsible for the activity of the crude extract prepared from the culture of Talaromyces sp. SY2250 in rice medium.
{"title":"Novel metabolites from the Mariana Trench-derived fungus <i>Talaromyces</i> sp. SY2250.","authors":"Xin Liu, Mingzhu Ma, Yura Ha, Nan Wang, Yufang Zhou, Zhizhen Zhang","doi":"10.1080/14786419.2024.2412305","DOIUrl":"https://doi.org/10.1080/14786419.2024.2412305","url":null,"abstract":"<p><p>Four previously undescribed compounds talaromyester A (<b>1</b>) and purpuresters C-E (<b>2</b><i>-</i><b>4</b>), together with known purpurester A (<b>5</b>) and purpuride G (<b>6</b>), were isolated from the metabolites produced by the Mariana Trench sediment-derived fungus <i>Talaromyces</i> sp. SY2250. Compounds <b>2</b><i>-</i><b>5</b>, two pairs of racemates, were separated on a chiral HPLC column. Structures of the isolated compounds were determined based on their HRESIMS data, extensive NMR spectroscopic analyses, and optical rotation calculations. Purpuride G (<b>6</b>) showed antiproliferative activity against glioma cells and may be the main active compound responsible for the activity of the crude extract prepared from the culture of <i>Talaromyces</i> sp. SY2250 in rice medium.</p>","PeriodicalId":18990,"journal":{"name":"Natural Product Research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375657","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}
This study examined five plants (Xylopia aethiopica, Agave sisalana, Hardwickia binata, Hedysarum alpinum, and Toxicodendron vernicifluum) for their potential to address insulin resistance in type 2 diabetes. In-vitro assays showed that H. binata leaves and H. alpinum flowers inhibited α-glucosidase and α-amylase while enhancing glucose uptake in normal and insulin-resistant HepG2 cells. Phytochemical screening and SPE purification identified the key constituents responsible for the effects. The chromatographic and spectral analysis confirmed flavonoids in H. binata (myricetin, isorhamnetin, quercetin, kaempferol, and catechin) and H. alpinum (luteolin, quercetin, kaempferol, and apigenin). Myricetin, isorhamnetin, and luteolin significantly increased glucose uptake, enhanced hexokinase and pyruvate kinase activities, and promoted IRec and IRS-1 phosphorylation, modulating insulin signalling. They activated AMPK and Akt, with molecular docking confirming strong AMPK binding. These findings suggest that H. binata, H. alpinum, and their flavonoids are promising candidates for managing insulin resistance and type 2 diabetes, warranting further research.
{"title":"Targeting insulin resistance: myricetin and isorhamnetin from <i>Hardwickia binata</i>, and luteolin from <i>Hedysarum alpinum</i> enhance glucose uptake and AMPK signaling in HepG2 cells.","authors":"Shiva Shankar Reddy Nimmala, Sreenu Thupakula, Raju Padiya","doi":"10.1080/14786419.2024.2411361","DOIUrl":"https://doi.org/10.1080/14786419.2024.2411361","url":null,"abstract":"<p><p>This study examined five plants (<i>Xylopia aethiopica, Agave sisalana, Hardwickia binata, Hedysarum alpinum, and Toxicodendron vernicifluum</i>) for their potential to address insulin resistance in type 2 diabetes. <i>In-vitro</i> assays showed that <i>H. binata</i> leaves and <i>H. alpinum</i> flowers inhibited α-glucosidase and α-amylase while enhancing glucose uptake in normal and insulin-resistant HepG2 cells. Phytochemical screening and SPE purification identified the key constituents responsible for the effects. The chromatographic and spectral analysis confirmed flavonoids in <i>H. binata</i> (myricetin, isorhamnetin, quercetin, kaempferol, and catechin) and <i>H. alpinum</i> (luteolin, quercetin, kaempferol, and apigenin). Myricetin, isorhamnetin, and luteolin significantly increased glucose uptake, enhanced hexokinase and pyruvate kinase activities, and promoted IRec and IRS-1 phosphorylation, modulating insulin signalling. They activated AMPK and Akt, with molecular docking confirming strong AMPK binding. These findings suggest that <i>H. binata</i>, <i>H. alpinum</i>, and their flavonoids are promising candidates for managing insulin resistance and type 2 diabetes, warranting further research.</p>","PeriodicalId":18990,"journal":{"name":"Natural Product Research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372357","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}
Pub Date : 2024-10-04DOI: 10.1080/14786419.2024.2410415
Jinyu Yu, Wen Yu, Xingan Wu, Jing Han
Schsphenines A (1) and B (2), two new lignans were isolated from the fruit of Schisandra sphenanthera, together with six known ones respectively identified as schisanhenol (3), methylgomisin O (4), wuweilignan E (5), neglschisandrin E (6), schisandrin A (7) and schisandrin B (8). The structures of isolated compounds were determined by UV, IR, HR-ESI-MS, NMR, ORD analysis and quantum chemical calculation. The in vitro cardioprotective activities of all compounds were studied on H2O2-injury H9C2 cells using the MTT method. Compound 1 exhibited a considerable protective effect with cell viability in 79.94 ± 2.36%. This research provided useful information for the utilisation of S. sphenanthera as the TCM.
{"title":"Schsphenines A and B, two new lignans from the fruit of <i>Schisandra sphenanthera</i> with cardioprotective Activities.","authors":"Jinyu Yu, Wen Yu, Xingan Wu, Jing Han","doi":"10.1080/14786419.2024.2410415","DOIUrl":"https://doi.org/10.1080/14786419.2024.2410415","url":null,"abstract":"<p><p>Schsphenines A (<b>1</b>) and B (<b>2</b>), two new lignans were isolated from the fruit of <i>Schisandra sphenanthera</i>, together with six known ones respectively identified as schisanhenol (<b>3</b>), methylgomisin O (<b>4</b>), wuweilignan E (<b>5</b>), neglschisandrin E (<b>6</b>), schisandrin A (<b>7</b>) and schisandrin B (<b>8</b>). The structures of isolated compounds were determined by UV, IR, HR-ESI-MS, NMR, ORD analysis and quantum chemical calculation. The <i>in vitro</i> cardioprotective activities of all compounds were studied on H<sub>2</sub>O<sub>2</sub>-injury H9C2 cells using the MTT method. Compound <b>1</b> exhibited a considerable protective effect with cell viability in 79.94 ± 2.36%. This research provided useful information for the utilisation of <i>S. sphenanthera</i> as the TCM.</p>","PeriodicalId":18990,"journal":{"name":"Natural Product Research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375658","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}
A new isocoumarin, 8-hydroxy-3-methyliscoumarin-6-yl acetate (1), was isolated together with five known compounds from sponge endophytic fungus Aspergillus ochraceopetaliformis. The structure of the new compound was established based on 1D and 2D NMR spectral analysis. Compounds 1-6 were evaluated for their cytotoxic activities and antimicrobial activities. Compounds 1 and 6 display cytotoxic activities against mouse melanoma cells B16 with IC50 values 72.5 ± 2.6 and 1.0 ± 0.5 µM, respectively. Compounds 4 and 5 displayed faint antimicrobial activities of Bacillus subtilis, Micrococcus luteus and Staphylococcus aureus.
{"title":"A new isocoumarin from sponge endophytic fungus <i>Aspergillus ochraceopetaliformis</i> with cytotoxic activity.","authors":"Ruitong Zhong, Chuanling Shi, Xiaoyun Wu, Yiting Zou, Jun Li, Yongqian Liang","doi":"10.1080/14786419.2024.2411373","DOIUrl":"https://doi.org/10.1080/14786419.2024.2411373","url":null,"abstract":"<p><p>A new isocoumarin, 8-hydroxy-3-methyliscoumarin-6-yl acetate (<b>1</b>), was isolated together with five known compounds from sponge endophytic fungus <i>Aspergillus ochraceopetaliformis.</i> The structure of the new compound was established based on 1D and 2D NMR spectral analysis. Compounds <b>1-6</b> were evaluated for their cytotoxic activities and antimicrobial activities. Compounds <b>1</b> and <b>6</b> display cytotoxic activities against mouse melanoma cells B16 with IC<sub>50</sub> values 72.5 ± 2.6 and 1.0 ± 0.5 <i>µ</i>M, respectively. Compounds <b>4</b> and <b>5</b> displayed faint antimicrobial activities of <i>Bacillus subtilis</i>, <i>Micrococcus luteus</i> and <i>Staphylococcus aureus</i>.</p>","PeriodicalId":18990,"journal":{"name":"Natural Product Research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365862","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}
The diversity of lignan small molecules derived from podophyllotoxin, a non-covalent tubulin inhibitor isolated from the Podophyllum family, has led to the clinical development of FDA-approved anticancer agents etoposide and teniposide. While these two compounds share the same tetracyclic core as podophyllotoxin, two subtle structural changes-4' demethylation on the aromatic ring and stereospecific glycosylation at the C-4 hydroxyl-result in an alternate biological mechanism. Given the immense pharmacological importance of altering the C-4 position, we synthesised and evaluated a systematic library of diversified esters to establish a structure-activity relationship regarding modification at C-4 on the properties of podophyllotoxin. We determined the biological activity of these esters through cell viability assays, computer docking models, tubulin polymerisation assays, and cell cycle analysis. Altogether, we demonstrate that increasing steric hindrance at C-4 leads to a loss in potency against human cancer cells but has a significantly lesser impact on cell-free tubulin inhibition.
{"title":"C-4 analogues of podophyllotoxin as tubulin inhibitors: synthesis, biological evaluation, and structure-activity relationship.","authors":"Breanna Lu, Lexi Xu, Harriet Chen, Grace Yu, Kimberly Khow, Stella Yang, Arushi Dinker, Edward Njoo","doi":"10.1080/14786419.2024.2410410","DOIUrl":"https://doi.org/10.1080/14786419.2024.2410410","url":null,"abstract":"<p><p>The diversity of lignan small molecules derived from podophyllotoxin, a non-covalent tubulin inhibitor isolated from the Podophyllum family, has led to the clinical development of FDA-approved anticancer agents etoposide and teniposide. While these two compounds share the same tetracyclic core as podophyllotoxin, two subtle structural changes-4' demethylation on the aromatic ring and stereospecific glycosylation at the C-4 hydroxyl-result in an alternate biological mechanism. Given the immense pharmacological importance of altering the C-4 position, we synthesised and evaluated a systematic library of diversified esters to establish a structure-activity relationship regarding modification at C-4 on the properties of podophyllotoxin. We determined the biological activity of these esters through cell viability assays, computer docking models, tubulin polymerisation assays, and cell cycle analysis. Altogether, we demonstrate that increasing steric hindrance at C-4 leads to a loss in potency against human cancer cells but has a significantly lesser impact on cell-free tubulin inhibition.</p>","PeriodicalId":18990,"journal":{"name":"Natural Product Research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365867","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}
Pub Date : 2024-10-03DOI: 10.1080/14786419.2024.2410420
Hongmin Xia, Xiao-Lei Du, Hong-Xiang Lou, Ping Wang
Two new carbazole alkaloids clauemarazole H (1) and clauemarazole I (2) were isolated from the stems of Clausena emarginata C. C. Huang. Their structures were confirmed by comprehensive spectroscopic analyses, and the absolute configurations were determined based on ECD experiments. The two compounds were evaluated for their neuroprotective effects against rotenone-induced damage in PC12 cells but did not exhibit any significant activity.
从Clausena emarginata C. C. Huang的茎中分离出两种新的咔唑生物碱clauemarazole H (1)和clauemarazole I (2)。通过综合光谱分析确认了它们的结构,并根据 ECD 实验确定了绝对构型。评估了这两种化合物对 PC12 细胞中由鱼藤酮诱导的神经损伤的保护作用,但未显示出任何显著的活性。
{"title":"A pair of enantiotropic carbazole alkaloids from the stems of <i>Clausena emarginata</i> C. C. Huang.","authors":"Hongmin Xia, Xiao-Lei Du, Hong-Xiang Lou, Ping Wang","doi":"10.1080/14786419.2024.2410420","DOIUrl":"https://doi.org/10.1080/14786419.2024.2410420","url":null,"abstract":"<p><p>Two new carbazole alkaloids clauemarazole H (<b>1</b>) and clauemarazole I (<b>2</b>) were isolated from the stems of <i>Clausena emarginata</i> C. C. Huang. Their structures were confirmed by comprehensive spectroscopic analyses, and the absolute configurations were determined based on ECD experiments. The two compounds were evaluated for their neuroprotective effects against rotenone-induced damage in PC12 cells but did not exhibit any significant activity.</p>","PeriodicalId":18990,"journal":{"name":"Natural Product Research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365863","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}
Pub Date : 2024-10-03DOI: 10.1080/14786419.2024.2410416
Prithviraj T
{"title":"Enhancing cancer therapy with curcumin: a versatile natural compound with multiple benefits.","authors":"Prithviraj T","doi":"10.1080/14786419.2024.2410416","DOIUrl":"https://doi.org/10.1080/14786419.2024.2410416","url":null,"abstract":"","PeriodicalId":18990,"journal":{"name":"Natural Product Research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365869","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}