Jianlin Li, Xue-Ying Zhang, Han Xu, Min Yang, Yu-Qin Gu, Cheng Ge, Gui Xin Wu
Mangrove-derived actinomycetes are prolific chemical sources of complex and novel natural products, providing an excellent chance for new drug discovery. The chemical investigation of the mangrove-derived Streptomycessundarbansensis 06037, led to the discovery of two previously undescribed enone fatty acids (1-2), one new phenylpropionate derivate (3), along with the isolation of the ten known components (4-13). Those chemical structures of isolates were elucidated on the basis of the analysis of diverse spectroscopic data. Initial anti-inflammatory tests of 1-3 in lipopolysaccharide (LPS)-activated RAW 264.7 murine macrophage cells revealed that compound 1 possess significant inhibitory effect on the production of Nitro oxidase (NO), with the IC50 value around 15.33 ± 1.32 μM, together with the suppression of NF-κB phosphorylation and reducing the release of oxygen species (ROS) in RAW 264.7 macrophages, those results indicated that compound 1 may exert its anti-inflammatory activity through a reduction in ROS level and the suppression of NF-κB activation pathway.
{"title":"Anti-inflammatory Fatty Acid Derivatives From Mangrove-derived Actinomycetes Streptomyces sp.","authors":"Jianlin Li, Xue-Ying Zhang, Han Xu, Min Yang, Yu-Qin Gu, Cheng Ge, Gui Xin Wu","doi":"10.1002/cbdv.202401946","DOIUrl":"https://doi.org/10.1002/cbdv.202401946","url":null,"abstract":"<p><p>Mangrove-derived actinomycetes are prolific chemical sources of complex and novel natural products, providing an excellent chance for new drug discovery. The chemical investigation of the mangrove-derived Streptomycessundarbansensis 06037, led to the discovery of two previously undescribed enone fatty acids (1-2), one new phenylpropionate derivate (3), along with the isolation of the ten known components (4-13). Those chemical structures of isolates were elucidated on the basis of the analysis of diverse spectroscopic data. Initial anti-inflammatory tests of 1-3 in lipopolysaccharide (LPS)-activated RAW 264.7 murine macrophage cells revealed that compound 1 possess significant inhibitory effect on the production of Nitro oxidase (NO), with the IC50 value around 15.33 ± 1.32 μM, together with the suppression of NF-κB phosphorylation and reducing the release of oxygen species (ROS) in RAW 264.7 macrophages, those results indicated that compound 1 may exert its anti-inflammatory activity through a reduction in ROS level and the suppression of NF-κB activation pathway.</p>","PeriodicalId":9878,"journal":{"name":"Chemistry & Biodiversity","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496048","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}
Four new isocoumarin derivatives 12-O-acetyl-isocitreoisocoumarinol (1), (+)-(10R)-O-acetyl-diaportinol (2-a), (-)-(10S)-O-acetyl-diaportinol (2-b), peyroisocoumarin E (3) and new stereoconfigurations of three isocoumarin derivatives desmethyldichlorodiaportinol A (4), threo-monochlorodiaportinol A (5-a), erytheo-monochlorodiaportinol A (5-b), together with nine known ones (6-14), were separated from the rice fermentation of endophytic fungus Diaporthe arengae M2 isolated from Camellia oleifera. The structures of new compounds were determined by extensive spectroscopic analyses including nuclear magnetic resonance (NMR) and high resolution electrospray ionization mass spectroscopy (HR-ESI-MS). Compounds 4, 7, 8, 12, 13 exhibited definite inhibition against five strains of bacteria with the MIC values range from 16 μg/mL to 64 μg/mL.
四种新的异香豆素衍生物 12-O-acetyl-isocitreoisocoumarinol (1)、(+)-(10R)-O-乙酰基-diaportinol (2-a)、(-)-(10S)-O-乙酰基-diaportinol (2-b)、peyroisocoumarin E (3) 和三种异香豆素衍生物 desmethyldichlorodiaportinol A (4) 的新立体构型、从油茶内生真菌 Diaporthe arengae M2 的水稻发酵产物中分离出了新的立体构型的三种异香豆素衍生物去甲二氯二香豆素醇 A(4)、三单氯二香豆素醇 A(5-a)、二单氯二香豆素醇 A(5-b)以及九种已知的异香豆素衍生物(6-14)。通过广泛的光谱分析,包括核磁共振(NMR)和高分辨电喷雾质谱(HR-ESI-MS),确定了新化合物的结构。化合物 4、7、8、12 和 13 对五种菌株具有明确的抑制作用,其 MIC 值范围为 16 μg/mL 至 64 μg/mL。
{"title":"New Isocoumarins from An Endophytic Fungal Strain Diaporthe arengae M2 and Their Antibacterial Activities.","authors":"Zhao Youxing, De-Sui Liu, Qing-Yun Ma, Li Yang, Qing-Yi Xie, Hao-Fu Dai, Jun-Feng Zhang, You-Gen Wu","doi":"10.1002/cbdv.202402293","DOIUrl":"https://doi.org/10.1002/cbdv.202402293","url":null,"abstract":"<p><p>Four new isocoumarin derivatives 12-O-acetyl-isocitreoisocoumarinol (1), (+)-(10R)-O-acetyl-diaportinol (2-a), (-)-(10S)-O-acetyl-diaportinol (2-b), peyroisocoumarin E (3) and new stereoconfigurations of three isocoumarin derivatives desmethyldichlorodiaportinol A (4), threo-monochlorodiaportinol A (5-a), erytheo-monochlorodiaportinol A (5-b), together with nine known ones (6-14), were separated from the rice fermentation of endophytic fungus Diaporthe arengae M2 isolated from Camellia oleifera. The structures of new compounds were determined by extensive spectroscopic analyses including nuclear magnetic resonance (NMR) and high resolution electrospray ionization mass spectroscopy (HR-ESI-MS). Compounds 4, 7, 8, 12, 13 exhibited definite inhibition against five strains of bacteria with the MIC values range from 16 μg/mL to 64 μg/mL.</p>","PeriodicalId":9878,"journal":{"name":"Chemistry & Biodiversity","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496057","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}
Simonetta Cristina Di Simone, Sakina Yagi, Laura Acquaticci, Nilofar Nilofar, Alessandra Acquaviva, Giustino Orlando, Filippo Maggi, Luigi Menghini, Claudio Ferrante, Gokhan Zengin, Giovanni Caprioli, Rıdvan Polat, Annalisa Chiavaroli
Eremurus spectabilis is widespread and used primarily for medicinal and culinary purposes. This study aimed to evaluate the chemical composition, antiradical and antioxidant activities, enzyme inhibitory activities, and anti-inflammatory properties of various extracts from the aerial parts of E. spectabilis. Various assays were used to investigate the antioxidant and enzyme inhibitory properties. The chemical composition of the tested extracts was analyzed using High-Performance Liquid Chromatography-Electrospray Ionization Tandem Mass Spectrometry (HPLC-ESI-MS/MS). Additionally, the extracts were tested on isolated mouse colon tissue challenged with E. coli lipopolysaccharide (LPS) to replicate the inflammation and oxidative stress burden characteristic of inflammatory bowel diseases. In the chemical composition, vanillic, ferulic, 4-hydroxybenzoic acids were the prominent compounds. The greatest antioxidant activity was observed in the methanol and water extracts from the aerial parts. Enzyme inhibition tests showed that the ethyl acetate extract had the highest anti-acetylcholinesterase activity. The gene expression of pro-inflammatory cyclooxygenase-2 (COX-2) and pro-oxidant inducible nitric oxide synthase (iNOS) biomarkers were assayed. Among the extracts, the methanol extract was the most effective in blunting LPS-induced gene expression of COX-2. E. spectabilis may serve as a valuable source of phytochemicals for combating oxidative stress and inflammation-driven diseases, with a particular emphasis on colon inflammatory condition.
{"title":"Investigation of the chemical composition and biological activities of Eremurus spectabilis M. Bieb through antioxidant, enzyme inhibition, COX-2 and iNOS assessment.","authors":"Simonetta Cristina Di Simone, Sakina Yagi, Laura Acquaticci, Nilofar Nilofar, Alessandra Acquaviva, Giustino Orlando, Filippo Maggi, Luigi Menghini, Claudio Ferrante, Gokhan Zengin, Giovanni Caprioli, Rıdvan Polat, Annalisa Chiavaroli","doi":"10.1002/cbdv.202401881","DOIUrl":"10.1002/cbdv.202401881","url":null,"abstract":"<p><p>Eremurus spectabilis is widespread and used primarily for medicinal and culinary purposes. This study aimed to evaluate the chemical composition, antiradical and antioxidant activities, enzyme inhibitory activities, and anti-inflammatory properties of various extracts from the aerial parts of E. spectabilis. Various assays were used to investigate the antioxidant and enzyme inhibitory properties. The chemical composition of the tested extracts was analyzed using High-Performance Liquid Chromatography-Electrospray Ionization Tandem Mass Spectrometry (HPLC-ESI-MS/MS). Additionally, the extracts were tested on isolated mouse colon tissue challenged with E. coli lipopolysaccharide (LPS) to replicate the inflammation and oxidative stress burden characteristic of inflammatory bowel diseases. In the chemical composition, vanillic, ferulic, 4-hydroxybenzoic acids were the prominent compounds. The greatest antioxidant activity was observed in the methanol and water extracts from the aerial parts. Enzyme inhibition tests showed that the ethyl acetate extract had the highest anti-acetylcholinesterase activity. The gene expression of pro-inflammatory cyclooxygenase-2 (COX-2) and pro-oxidant inducible nitric oxide synthase (iNOS) biomarkers were assayed. Among the extracts, the methanol extract was the most effective in blunting LPS-induced gene expression of COX-2. E. spectabilis may serve as a valuable source of phytochemicals for combating oxidative stress and inflammation-driven diseases, with a particular emphasis on colon inflammatory condition.</p>","PeriodicalId":9878,"journal":{"name":"Chemistry & Biodiversity","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459238","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}
Hemat Kalifa, Mohmed Abd El Aziz, Mohamed Radwan, Ashraf Sediek
This study aimed to synthesize C3-indole derivatives linked to various heterocyclic scaffolds, including thiophenes, thiazolidine-4-ones, and 1,3,4-thiadiazoles, via the reaction of ethylthioacetanilide 2 with different α-haloketones.The structures of the target compounds were established using 1H and 13C nuclear magnetic resonance spectroscopy, mass spectrometry, infrared spectroscopy, and elemental analysis. The synthesized compounds were tested for antimicrobial activity against different microbes: S. aureus ATCC 6538 (Gram-positive bacteria), E. coli ATCC 25933 (Gram-negative bacteria), C. albicans ATCC 10231 (yeast), and fungi (A. niger NRRL-A326). Thiophene 6a, thiazolidine-4-one 8, and compound 10d exhibited the highest antimicrobial activities. The molecular docking study showed that compounds 2, 4, 6a, and 6c had good binding energy and favorable binding modes of interactions with the DNA gyrase B enzymes (PDB: 3U2D) and (PDB: 1S14). The results showed that the NH group of the indole in compounds 2 and 4, together with the nitrile group (CN), played an important role in inhibiting DNA gyrase B of S. aureus, PDB: 3U2D. Furthermore, the NH of the indole ring, together with the ethylamino group of compound 2, was crucial in inhibiting DNA gyrase B of E. coli, PDB: 1S14. These results could inspire further development of indole derivatives as antimicrobial drugs.
{"title":"Synthesis, Biological Evaluation, and Molecular Docking Studies of Indole-Based Heterocyclic Scaffolds as Potential Antibacterial Agents.","authors":"Hemat Kalifa, Mohmed Abd El Aziz, Mohamed Radwan, Ashraf Sediek","doi":"10.1002/cbdv.202402325","DOIUrl":"https://doi.org/10.1002/cbdv.202402325","url":null,"abstract":"<p><p>This study aimed to synthesize C3-indole derivatives linked to various heterocyclic scaffolds, including thiophenes, thiazolidine-4-ones, and 1,3,4-thiadiazoles, via the reaction of ethylthioacetanilide 2 with different α-haloketones.The structures of the target compounds were established using 1H and 13C nuclear magnetic resonance spectroscopy, mass spectrometry, infrared spectroscopy, and elemental analysis. The synthesized compounds were tested for antimicrobial activity against different microbes: S. aureus ATCC 6538 (Gram-positive bacteria), E. coli ATCC 25933 (Gram-negative bacteria), C. albicans ATCC 10231 (yeast), and fungi (A. niger NRRL-A326). Thiophene 6a, thiazolidine-4-one 8, and compound 10d exhibited the highest antimicrobial activities. The molecular docking study showed that compounds 2, 4, 6a, and 6c had good binding energy and favorable binding modes of interactions with the DNA gyrase B enzymes (PDB: 3U2D) and (PDB: 1S14). The results showed that the NH group of the indole in compounds 2 and 4, together with the nitrile group (CN), played an important role in inhibiting DNA gyrase B of S. aureus, PDB: 3U2D. Furthermore, the NH of the indole ring, together with the ethylamino group of compound 2, was crucial in inhibiting DNA gyrase B of E. coli, PDB: 1S14. These results could inspire further development of indole derivatives as antimicrobial drugs.</p>","PeriodicalId":9878,"journal":{"name":"Chemistry & Biodiversity","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459250","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}
Forty-nine compounds, including six previously unknown together with forty-three known ones, were isolated from the fruits of Foeniculum vulgare Mill. Their structures were elucidated using high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), infrared spectroscopy (IR), ultraviolet-visible spectroscopy (UV), nuclear magnetic resonance (NMR), and electronic circular dichroism (ECD) methods. All isolates were evaluated their anti-inflammatory activity. The results indicated that compounds 1, 6, 35 and 45 inhibit lipopolysaccharide(LPS)-induced nitric oxide production in RAW 264.7 macrophages with IC50 values of 17.13 ± 0.74, 14.40 ± 0.54, 112.13 ± 2.08 and 77.02 ± 3.62 μg/mL, respectively. Moreover, the potential targets of the four active ingredients were explored through network pharmacology, revealing that SRC, TP53, AKT1, and PIK3CA may serve as key anti-inflammatory targets. To confirm the potential binding mode, molecular docking was employed, which demonstrated that all active targets except SRC exhibited favorable binding energy with compound 35. Additionally, the anti-inflammatory activities of compounds 1-6 were first observed in this experiment.
{"title":"Anti-inflammatory Activities and Mechanisms of New Compounds Isolated from the Fruits of Foeniculum vulgare Mill.","authors":"Dong Weimao, Yun-Tao Zhang, Hai-Ming Wang, Mao-Xin Deng, Zhang-Xian Chen, Hong-Ping He, Fa-Wu Dong","doi":"10.1002/cbdv.202401788","DOIUrl":"https://doi.org/10.1002/cbdv.202401788","url":null,"abstract":"<p><p>Forty-nine compounds, including six previously unknown together with forty-three known ones, were isolated from the fruits of Foeniculum vulgare Mill. Their structures were elucidated using high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), infrared spectroscopy (IR), ultraviolet-visible spectroscopy (UV), nuclear magnetic resonance (NMR), and electronic circular dichroism (ECD) methods. All isolates were evaluated their anti-inflammatory activity. The results indicated that compounds 1, 6, 35 and 45 inhibit lipopolysaccharide(LPS)-induced nitric oxide production in RAW 264.7 macrophages with IC50 values of 17.13 ± 0.74, 14.40 ± 0.54, 112.13 ± 2.08 and 77.02 ± 3.62 μg/mL, respectively. Moreover, the potential targets of the four active ingredients were explored through network pharmacology, revealing that SRC, TP53, AKT1, and PIK3CA may serve as key anti-inflammatory targets. To confirm the potential binding mode, molecular docking was employed, which demonstrated that all active targets except SRC exhibited favorable binding energy with compound 35. Additionally, the anti-inflammatory activities of compounds 1-6 were first observed in this experiment.</p>","PeriodicalId":9878,"journal":{"name":"Chemistry & Biodiversity","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459222","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}
Yaqing Wu, Jamal A H Kowah, Tianqi Zhu, Yufang Li, Lisheng Wang, Haixia Yu
To further explore more active compounds, Matrine and Isatin derivatives have exhibited diverse biological activities. In this study, twenty-one 15-site matrine based isatohydrazone derivatives were designed, synthesized, and evaluated in their biological activities. In vitro, antiproliferative activity assays were carried out using the MTT assay against three human cell lines: human cervical cancer cells (HeLa), human colon cancer cells (HCT116), and non-small cell lung cancer cells (A549). Most of the target compounds displayed strong antiproliferative activities against the tested cells, surpassing matrine. Compound 5a exhibited the strongest antiproliferative activity, with IC50 values of 9.02±0.33 μM, 10.49±1.09 μM, and 15.23±0.12 μM against the respective cell lines. Experiments on cell cycle and apoptosis indicated that compound 5a induces cell cycle arrest in the G0/G1 phase and promotes cell apoptosis. Compound 5a also significantly inhibited cell colony formation and migration. Molecular docking experiments showed that compound 5a can form hydrogen bonds and hydrophobic interactions with the EGFR-related protein 7AEI.
{"title":"Synthesis, Biological activities, and Molecular docking Studies of 15-site Matrine Based Isatohydrazone Derivatives as Potential Anticancer Agents.","authors":"Yaqing Wu, Jamal A H Kowah, Tianqi Zhu, Yufang Li, Lisheng Wang, Haixia Yu","doi":"10.1002/cbdv.202402065","DOIUrl":"https://doi.org/10.1002/cbdv.202402065","url":null,"abstract":"<p><p>To further explore more active compounds, Matrine and Isatin derivatives have exhibited diverse biological activities. In this study, twenty-one 15-site matrine based isatohydrazone derivatives were designed, synthesized, and evaluated in their biological activities. In vitro, antiproliferative activity assays were carried out using the MTT assay against three human cell lines: human cervical cancer cells (HeLa), human colon cancer cells (HCT116), and non-small cell lung cancer cells (A549). Most of the target compounds displayed strong antiproliferative activities against the tested cells, surpassing matrine. Compound 5a exhibited the strongest antiproliferative activity, with IC50 values of 9.02±0.33 μM, 10.49±1.09 μM, and 15.23±0.12 μM against the respective cell lines. Experiments on cell cycle and apoptosis indicated that compound 5a induces cell cycle arrest in the G0/G1 phase and promotes cell apoptosis. Compound 5a also significantly inhibited cell colony formation and migration. Molecular docking experiments showed that compound 5a can form hydrogen bonds and hydrophobic interactions with the EGFR-related protein 7AEI.</p>","PeriodicalId":9878,"journal":{"name":"Chemistry & Biodiversity","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459249","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}
Globally, cancer is one of the leading causes of death. Resistance to conventional medications, such as chemotherapy and radiation, continues to be a significant challenge in the treatment of cancer despite the availability of numerous medicines. Therefore, the highest priority is to hunt for new therapeutic agents. Transforming growth factor-beta is a pivotal regulatory cytokine that exerts significant influence over cellular processes, particularly emphasizing its role in facilitating and modulating cell proliferation. TGFβ1, identified as most promising active site of the TGF-β signaling, is a potent drug target site that has garnered wide attention for developing new anticancer agents. The present investigation investigates the potential phytochemicals as TGFβR1 inhibitors. The SB431542 complexed TGFβR1 protein model was used to screen the natural product database to obtain a compound with high binding potential. NPC247629 has emerged as the best-scored compound among all the screened compounds, demonstrating the highest affinity towards the TGFβR1 regarding docking score -17.54 kcal/mol. The MD simulation study indicated that all proposed hits are retained inside the receptor in dynamic states. The best-screened hits, NPC247629 and NPC60735, have excellent binding affinity and hold a massive potential for TGFβR1 inhibition, paving the way for promising future investigations in cancer treatment.
{"title":"Identification of Potential Inhibitors of TGFβR1 for the treatment of Cancer through Structure-based virtual screening and Molecular dynamics simulations.","authors":"Saumya Rastogi, Shashank Shekhar Mishra, Lakhveer Singh, Neeraj Kumar","doi":"10.1002/cbdv.202401981","DOIUrl":"https://doi.org/10.1002/cbdv.202401981","url":null,"abstract":"<p><p>Globally, cancer is one of the leading causes of death. Resistance to conventional medications, such as chemotherapy and radiation, continues to be a significant challenge in the treatment of cancer despite the availability of numerous medicines. Therefore, the highest priority is to hunt for new therapeutic agents. Transforming growth factor-beta is a pivotal regulatory cytokine that exerts significant influence over cellular processes, particularly emphasizing its role in facilitating and modulating cell proliferation. TGFβ1, identified as most promising active site of the TGF-β signaling, is a potent drug target site that has garnered wide attention for developing new anticancer agents. The present investigation investigates the potential phytochemicals as TGFβR1 inhibitors. The SB431542 complexed TGFβR1 protein model was used to screen the natural product database to obtain a compound with high binding potential. NPC247629 has emerged as the best-scored compound among all the screened compounds, demonstrating the highest affinity towards the TGFβR1 regarding docking score -17.54 kcal/mol. The MD simulation study indicated that all proposed hits are retained inside the receptor in dynamic states. The best-screened hits, NPC247629 and NPC60735, have excellent binding affinity and hold a massive potential for TGFβR1 inhibition, paving the way for promising future investigations in cancer treatment.</p>","PeriodicalId":9878,"journal":{"name":"Chemistry & Biodiversity","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459234","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}
David Morales-Morales, Antonino Arenaza-Corona, Paola Sánchez-Portillo, Lucero González-Sebastián, Arturo Sánchez-Mora, Brian Monroy-Torres, Teresa Ramírez-Apan, Nicolás Puentes-Díaz, Jorge Alí-Torres, Victor Barba, Viviana Reyes-Marquez
The synthesis of three novel curcumin derivative compounds, featuring aza-crown ether macrocycles of various sizes (aza-12-crown-4, aza-15-crown-5, and aza-18-crown-6), is described. The incorporation of these aza-crown macrocycles significantly enhances their water solubility, positioning them as groundbreaking instances of curcumin derivatives that are fully soluble in aqueous environments. These curcumin ligands (L1, L2, and L3) were then reacted with zinc acetate to afford the coordination metal complexes (L1-Zn, L2-Zn, and L3-Zn). Comprehensive characterization of all compounds was achieved using various analytical techniques, including 1D and 2D NMR spectroscopy, ATR-FTIR spectroscopy, mass spectrometry (ESI+), elemental analysis and UV-Vis spectroscopy. The in vitro cytotoxic activity of both, ligands and complexes were evaluated on three human cancer cell lines (U-251, MCF-7, and SK-LU-1). Compared to conventional curcumin, these compounds demonstrated improved antiproliferative potential. Additionally, a wound healing assay was conducted to assess their antimigration properties. The obtained results suggest that these modifications to the curcumin structure represent a promising approach for developing therapeutic agents with enhanced cytotoxic properties.
{"title":"Water-Soluble Curcumin Derivatives Including Aza-Crown Ether Macrocycles as Enhancers of their Cytotoxic Activity.","authors":"David Morales-Morales, Antonino Arenaza-Corona, Paola Sánchez-Portillo, Lucero González-Sebastián, Arturo Sánchez-Mora, Brian Monroy-Torres, Teresa Ramírez-Apan, Nicolás Puentes-Díaz, Jorge Alí-Torres, Victor Barba, Viviana Reyes-Marquez","doi":"10.1002/cbdv.202402083","DOIUrl":"https://doi.org/10.1002/cbdv.202402083","url":null,"abstract":"<p><p>The synthesis of three novel curcumin derivative compounds, featuring aza-crown ether macrocycles of various sizes (aza-12-crown-4, aza-15-crown-5, and aza-18-crown-6), is described. The incorporation of these aza-crown macrocycles significantly enhances their water solubility, positioning them as groundbreaking instances of curcumin derivatives that are fully soluble in aqueous environments. These curcumin ligands (L1, L2, and L3) were then reacted with zinc acetate to afford the coordination metal complexes (L1-Zn, L2-Zn, and L3-Zn). Comprehensive characterization of all compounds was achieved using various analytical techniques, including 1D and 2D NMR spectroscopy, ATR-FTIR spectroscopy, mass spectrometry (ESI+), elemental analysis and UV-Vis spectroscopy. The in vitro cytotoxic activity of both, ligands and complexes were evaluated on three human cancer cell lines (U-251, MCF-7, and SK-LU-1). Compared to conventional curcumin, these compounds demonstrated improved antiproliferative potential. Additionally, a wound healing assay was conducted to assess their antimigration properties. The obtained results suggest that these modifications to the curcumin structure represent a promising approach for developing therapeutic agents with enhanced cytotoxic properties.</p>","PeriodicalId":9878,"journal":{"name":"Chemistry & Biodiversity","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459256","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}
Ivana Romão, Sônia Maria Costa Siqueira, Flávia Oliveira Monteiro da Silva Abreu, Hélcio Silva Dos Santos
The investigation of new drugs is slow and costly. Drug repositioning, like with Hydralazine (HDZ), an old antihypertensive, can accelerate the process. HDZ and its hydrazonic derivatives exhibit diverse biological activities, promising for new drugs. This review explores HDZ's repositioning potential and its derivatives' applications in various biological activities. It identified 70 relevant articles through database searches. HDZ shows potential in neurology, oncology, nephrology, and gynecology, with clinical trials up to Phase III. Hydralazine-valproate, marketed in Mexico, proves effective in combination with chemotherapy. Hydrazonic derivatives offer broad applications in medicine. Studying their structure-activity relationship can enhance efficacy. This review summarizes their properties and pharmacological activities succinctly.
{"title":"Hydralazine and Hydrazine Derivatives: Properties, Applications, and Repositioning Potential.","authors":"Ivana Romão, Sônia Maria Costa Siqueira, Flávia Oliveira Monteiro da Silva Abreu, Hélcio Silva Dos Santos","doi":"10.1002/cbdv.202401561","DOIUrl":"https://doi.org/10.1002/cbdv.202401561","url":null,"abstract":"<p><p>The investigation of new drugs is slow and costly. Drug repositioning, like with Hydralazine (HDZ), an old antihypertensive, can accelerate the process. HDZ and its hydrazonic derivatives exhibit diverse biological activities, promising for new drugs. This review explores HDZ's repositioning potential and its derivatives' applications in various biological activities. It identified 70 relevant articles through database searches. HDZ shows potential in neurology, oncology, nephrology, and gynecology, with clinical trials up to Phase III. Hydralazine-valproate, marketed in Mexico, proves effective in combination with chemotherapy. Hydrazonic derivatives offer broad applications in medicine. Studying their structure-activity relationship can enhance efficacy. This review summarizes their properties and pharmacological activities succinctly.</p>","PeriodicalId":9878,"journal":{"name":"Chemistry & Biodiversity","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459232","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 aim of study is to investigate the various mechanism-based antioxidant and anti-fungal properties of a hydroalcoholic extract of Ocimum basilicum L leaves. Additionally, conduct molecular docking to simultaneously validate in vitro activities. Also, perform ADMET analysis to know pharmacokinetic properties and its toxicity for its safety. Prior extract's qualitative analysis has been performed to identify the bioactive compounds by phytochemical tests and GC-MS analysis. Different mechanism-based in vitro antioxidant methods are studied; in different methods, different IC50 values have come, which revealed the extract's antioxidant potentials. The antifungal potential of the extract has been observed by performing a modified poison food assay and a time-killing curve assay. In silico analysis with the human peroxiredoxin 5 enzyme (PDB ID: 1HD2) and secreted aspartic proteinase (PDB ID: 2QZX), which predict extract biological activity, has shown promising results of Ocimum basilicum L extract. In silico findings confirm the in vitro experimental outcome of the extract. The different IC50 values of extracts in different mechanisms indicate their therapeutic potential, and that encourages further research in formulation development. The time-killing assay method gives information about a dynamic interaction between extract and microbial strain. Concentration-dependent antifungal studies have significance in formulation development for dose determination.
{"title":"In Vitro Antioxidant and Antifungal Activities of Extracts from Ocimum basilicum Leaves Validated by Molecular Docking and ADMET Analysis.","authors":"Neha Vijay, Mohamad Taleuzzaman, Sharwan Hudda, Nisha Choudhary","doi":"10.1002/cbdv.202401969","DOIUrl":"https://doi.org/10.1002/cbdv.202401969","url":null,"abstract":"<p><p>The aim of study is to investigate the various mechanism-based antioxidant and anti-fungal properties of a hydroalcoholic extract of Ocimum basilicum L leaves. Additionally, conduct molecular docking to simultaneously validate in vitro activities. Also, perform ADMET analysis to know pharmacokinetic properties and its toxicity for its safety. Prior extract's qualitative analysis has been performed to identify the bioactive compounds by phytochemical tests and GC-MS analysis. Different mechanism-based in vitro antioxidant methods are studied; in different methods, different IC50 values have come, which revealed the extract's antioxidant potentials. The antifungal potential of the extract has been observed by performing a modified poison food assay and a time-killing curve assay. In silico analysis with the human peroxiredoxin 5 enzyme (PDB ID: 1HD2) and secreted aspartic proteinase (PDB ID: 2QZX), which predict extract biological activity, has shown promising results of Ocimum basilicum L extract. In silico findings confirm the in vitro experimental outcome of the extract. The different IC50 values of extracts in different mechanisms indicate their therapeutic potential, and that encourages further research in formulation development. The time-killing assay method gives information about a dynamic interaction between extract and microbial strain. Concentration-dependent antifungal studies have significance in formulation development for dose determination.</p>","PeriodicalId":9878,"journal":{"name":"Chemistry & Biodiversity","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459235","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}