Stefano Dall'Acqua, Sakina Yagi, Stefania Sut, Abdullahi Ibrahim Uba, Sathish Kumar M. Ponniya, Ismail Koyuncu, Kenan Toprak, Mehmet Maruf Balos, Alevcan Kaplan, Uğur Çakılcıoğlu, Gokhan Zengin
Tanacetum nitens (Boiss. & Noë) Grierson is an aromatic perennial herb used in Turkish traditional medicine to treat headache, fever, and skin diseases. This study aimed to investigate the chemical composition, antioxidant, enzyme inhibition, and cytotoxic properties of T. nitens aerial parts. Organic solvent extracts were prepared by sequential maceration in hexane, dichloromethane, ethyl acetate, and methanol while aqueous extracts were obtained by maceration or infusion. Nuclear magnetic resonance (NMR) and LC-DAD-MS analysis allowed the identification and quantification of different phytoconstituents including parthenolide, tanacetol B, tatridin B, quinic acid derivatives, β-sitosterol, and glycoside derivatives of quercetin and luteolin. The type and amount of these phytochemicals recovered by each solvent were variable and significant enough to impact the biological activities of the plant. Methanolic and aqueous extracts displayed the highest scavenging and ions-reducing properties while the dichloromethane and ethyl acetate extracts exerted the best total antioxidant activity and metal chelating power. Results of enzyme inhibition activity showed that the hexane, ethyl acetate, and dichloromethane extracts had comparable anti-acetylcholinesterase activity and the latter extract revealed the highest anti-butyrylcholinesterase activity. The best α-amylase and α-glucosidase inhibition activities were obtained from the hexane extract. The dichloromethane and ethyl acetate extracts exhibited the highest cytotoxic effect against the prostate carcinoma DU-145 cells. In conclusion, these findings indicated that T. nitens can be a promising source of biomolecules with potential therapeutic applications.
{"title":"Combining chemical profiles and biological abilities of different extracts from Tanacetum nitens (Boiss. & Noë) Grierson using network pharmacology","authors":"Stefano Dall'Acqua, Sakina Yagi, Stefania Sut, Abdullahi Ibrahim Uba, Sathish Kumar M. Ponniya, Ismail Koyuncu, Kenan Toprak, Mehmet Maruf Balos, Alevcan Kaplan, Uğur Çakılcıoğlu, Gokhan Zengin","doi":"10.1002/ardp.202400194","DOIUrl":"10.1002/ardp.202400194","url":null,"abstract":"<p><i>Tanacetum nitens</i> (<span>Boiss. & Noë</span>) <span>Grierson</span> is an aromatic perennial herb used in Turkish traditional medicine to treat headache, fever, and skin diseases. This study aimed to investigate the chemical composition, antioxidant, enzyme inhibition, and cytotoxic properties of <i>T. nitens</i> aerial parts. Organic solvent extracts were prepared by sequential maceration in hexane, dichloromethane, ethyl acetate, and methanol while aqueous extracts were obtained by maceration or infusion. Nuclear magnetic resonance (NMR) and LC-DAD-MS analysis allowed the identification and quantification of different phytoconstituents including parthenolide, tanacetol B, tatridin B, quinic acid derivatives, β-sitosterol, and glycoside derivatives of quercetin and luteolin. The type and amount of these phytochemicals recovered by each solvent were variable and significant enough to impact the biological activities of the plant. Methanolic and aqueous extracts displayed the highest scavenging and ions-reducing properties while the dichloromethane and ethyl acetate extracts exerted the best total antioxidant activity and metal chelating power. Results of enzyme inhibition activity showed that the hexane, ethyl acetate, and dichloromethane extracts had comparable anti-acetylcholinesterase activity and the latter extract revealed the highest anti-butyrylcholinesterase activity. The best α-amylase and α-glucosidase inhibition activities were obtained from the hexane extract. The dichloromethane and ethyl acetate extracts exhibited the highest cytotoxic effect against the prostate carcinoma DU-145 cells. In conclusion, these findings indicated that <i>T. nitens</i> can be a promising source of biomolecules with potential therapeutic applications.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141320172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This review article offers an environmentally benign synthesis of 1,3,4-oxadiazole derivatives, with a focus on sustainable methodologies that have minimal impact on the environment. These derivatives, known for their diverse applications, have conventionally been associated with synthesis methods that utilize hazardous reagents and produce significant waste, thereby raising environmental concerns. The green synthesis of 1,3,4-oxadiazole derivatives employs renewable substrates, nontoxic catalysts, and mild reaction conditions, aiming to minimize the environmental impact. Innovative techniques such as catalyst-based, catalyst-free, electrochemical synthesis, green-solvent-mediated synthesis, grinding, microwave-mediated synthesis, and photosynthesis are implemented, providing benefits in terms of scalability, cost-effectiveness, and ease of purification. This review emphasizes the significance of sustainable methodologies in the synthesis of 1,3,4-oxadiazole and boots for continued exploration in this research domain.
{"title":"Eco-friendly approaches to 1,3,4-oxadiazole derivatives: A comprehensive review of green synthetic strategies","authors":"Drashti Shah, Ashish Patel","doi":"10.1002/ardp.202400185","DOIUrl":"10.1002/ardp.202400185","url":null,"abstract":"<p>This review article offers an environmentally benign synthesis of 1,3,4-oxadiazole derivatives, with a focus on sustainable methodologies that have minimal impact on the environment. These derivatives, known for their diverse applications, have conventionally been associated with synthesis methods that utilize hazardous reagents and produce significant waste, thereby raising environmental concerns. The green synthesis of 1,3,4-oxadiazole derivatives employs renewable substrates, nontoxic catalysts, and mild reaction conditions, aiming to minimize the environmental impact. Innovative techniques such as catalyst-based, catalyst-free, electrochemical synthesis, green-solvent-mediated synthesis, grinding, microwave-mediated synthesis, and photosynthesis are implemented, providing benefits in terms of scalability, cost-effectiveness, and ease of purification. This review emphasizes the significance of sustainable methodologies in the synthesis of 1,3,4-oxadiazole and boots for continued exploration in this research domain.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141320173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Benzothiazoles are a class of heterocycles with multiple applications as anticancer, antibiotic, antiviral, and anti-inflammatory agents. Benzothiazole is a privileged scaffold in drug discovery programs for modulating a variety of biological functions. This review focuses on the design and synthesis of new benzothiazole derivatives targeting hypoxic tumors. Cancer is a major health problem, being among the leading causes of death. Tumor-hypoxic areas promote proliferation, malignancy, and resistance to drug treatment, leading to the dysregulation of key signaling pathways that involve drug targets such as vascular endothelial growth factor, epidermal growth factor receptor, hepatocyte growth factor receptor, dual-specificity protein kinase, cyclin-dependent protein kinases, casein kinase 2, Rho-related coil formation protein kinase, tunica interna endothelial cell kinase, cyclooxygenase-2, adenosine kinase, lysophosphatidic acid acyltransferases, stearoyl-CoA desaturase, peroxisome proliferator-activated receptors, thioredoxin, heat shock proteins, and carbonic anhydrase IX/XII. In turn, they regulate angiogenesis, proliferation, differentiation, and cell survival, controlling the cell cycle, inflammation, the immune system, and metabolic alterations. A wide diversity of benzothiazoles were reported over the last years to interfere with various proteins involved in tumorigenesis and, more specifically, in hypoxic tumors. Many hypoxic targets are overexpressed as a result of the hypoxia-inducible factor activation cascade and may not be present in normal tissues, providing a potential strategy for selectively targeting hypoxic cancers.
{"title":"Benzothiazole derivatives in the design of antitumor agents","authors":"Niccolò Paoletti, Claudiu T. Supuran","doi":"10.1002/ardp.202400259","DOIUrl":"10.1002/ardp.202400259","url":null,"abstract":"<p>Benzothiazoles are a class of heterocycles with multiple applications as anticancer, antibiotic, antiviral, and anti-inflammatory agents. Benzothiazole is a privileged scaffold in drug discovery programs for modulating a variety of biological functions. This review focuses on the design and synthesis of new benzothiazole derivatives targeting hypoxic tumors. Cancer is a major health problem, being among the leading causes of death. Tumor-hypoxic areas promote proliferation, malignancy, and resistance to drug treatment, leading to the dysregulation of key signaling pathways that involve drug targets such as vascular endothelial growth factor, epidermal growth factor receptor, hepatocyte growth factor receptor, dual-specificity protein kinase, cyclin-dependent protein kinases, casein kinase 2, Rho-related coil formation protein kinase, tunica interna endothelial cell kinase, cyclooxygenase-2, adenosine kinase, lysophosphatidic acid acyltransferases, stearoyl-CoA desaturase, peroxisome proliferator-activated receptors, thioredoxin, heat shock proteins, and carbonic anhydrase IX/XII. In turn, they regulate angiogenesis, proliferation, differentiation, and cell survival, controlling the cell cycle, inflammation, the immune system, and metabolic alterations. A wide diversity of benzothiazoles were reported over the last years to interfere with various proteins involved in tumorigenesis and, more specifically, in hypoxic tumors. Many hypoxic targets are overexpressed as a result of the hypoxia-inducible factor activation cascade and may not be present in normal tissues, providing a potential strategy for selectively targeting hypoxic cancers.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141316180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Silvio Jakopec, Lejla F. Hamzic, Luka Bočkor, Iris Car, Berislav Perić, Srećko I. Kirin, Mirela Sedić, Silvana Raić-Malić
Among ruthenium complexes studied as anticancer metallodrugs, NKP-1339, NAMI-A, RM175, and RAPTA-C have already entered clinical trials due to their potent antitumor activity demonstrated in preclinical studies and reduced toxicity in comparison with platinum drugs. Considering the advantages of ruthenium-based anticancer drugs and the cytostatic activity of organometallic complexes with triazole- and coumarin-derived ligands, we set out to synthesize Ru(II) complexes of coumarin-1,2,3,-triazole hybrids (L) with the general formula [Ru(L)(p-cymene)(Cl)]ClO4. The molecular structure of the complex [Ru(2a)(p-cymene)(Cl)]ClO4 (2aRu) was determined by single-crystal X-ray diffraction, which confirmed the coordination of the ligand to the central ruthenium(II) cation by bidentate mode of coordination. Coordination with Ru(II) resulted in the enhancement of cytostatic activity in HepG2 hepatocellular carcinoma cells and PANC-1 pancreatic cancer cells. Coumarin derivative 2a positively regulated the expression and activity of c-Myc and NPM1 in RKO colon carcinoma cells, while the Ru(II) half-sandwich complex 2cRu induced downregulation of AKT and ERK signaling in PANC-1 cells concomitant with reduced intracellular levels of reactive oxygen species. Altogether, our findings indicated that coumarin-modified half-sandwich Ru(II) complexes held potential as anticancer agents against gastrointestinal malignancies.
{"title":"Coumarin-modified ruthenium complexes: Synthesis, characterization, and antiproliferative activity against human cancer cells","authors":"Silvio Jakopec, Lejla F. Hamzic, Luka Bočkor, Iris Car, Berislav Perić, Srećko I. Kirin, Mirela Sedić, Silvana Raić-Malić","doi":"10.1002/ardp.202400271","DOIUrl":"10.1002/ardp.202400271","url":null,"abstract":"<p>Among ruthenium complexes studied as anticancer metallodrugs, NKP-1339, NAMI-A, RM175, and RAPTA-C have already entered clinical trials due to their potent antitumor activity demonstrated in preclinical studies and reduced toxicity in comparison with platinum drugs. Considering the advantages of ruthenium-based anticancer drugs and the cytostatic activity of organometallic complexes with triazole- and coumarin-derived ligands, we set out to synthesize Ru(II) complexes of coumarin-1,2,3,-triazole hybrids (<b>L</b>) with the general formula [Ru(<b>L</b>)(<i>p</i>-cymene)(Cl)]ClO<sub>4</sub>. The molecular structure of the complex [Ru(<b>2a</b>)(<i>p</i>-cymene)(Cl)]ClO<sub>4</sub> (<b>2a</b><sub><b>Ru</b></sub>) was determined by single-crystal X-ray diffraction, which confirmed the coordination of the ligand to the central ruthenium(II) cation by bidentate mode of coordination. Coordination with Ru(II) resulted in the enhancement of cytostatic activity in HepG2 hepatocellular carcinoma cells and PANC-1 pancreatic cancer cells. Coumarin derivative <b>2a</b> positively regulated the expression and activity of c-Myc and NPM1 in RKO colon carcinoma cells, while the Ru(II) half-sandwich complex <b>2c</b><sub><b>Ru</b></sub> induced downregulation of AKT and ERK signaling in PANC-1 cells concomitant with reduced intracellular levels of reactive oxygen species. Altogether, our findings indicated that coumarin-modified half-sandwich Ru(II) complexes held potential as anticancer agents against gastrointestinal malignancies.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141304981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hager R. Nofal, Ahmed A. Al-Karmalawy, Ayman Abo Elmaaty, Mahmoud F. Ismail, Ali Khalil Ali, Eslam M. Abbass
A series of tetrahydrobenzo[b]thiophene derivatives was designed and synthesized as dual topoisomerase (Topo) I/II inhibitors implicating potential DNA intercalation. Ethyl-2-amino-3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophene-4-carboxylate (1) was prepared by modification of the Gewald reaction procedure using a Fe2O3 nanocatalyst and then it was used as a building block for the synthesis of tetrahydrobenzo[b]thiophene candidates (2–14). Interestingly, compound 14 showed the best cytotoxic potential against hepatocellular, colorectal, and breast cancer cell lines (IC50 = 7.79, 8.10, and 3.53 µM), respectively, surpassing doxorubicin at breast cancer (IC50 = 4.17 µM). Meanwhile, the Topo I and II inhibition assay displayed that compound 3 could exhibit the best inhibitory potential among the investigated candidates (IC50 = 25.26 and 10.01 nM), respectively, in comparison to camptothecin (IC50 = 28.34 nM) and doxorubicin (IC50 = 11.01 nM), as reference standards. In addition, the DNA intercalation assay showed that compound 14 could display the best binding affinity with an IC50 value of 77.82 µM in comparison to doxorubicin (IC50 = 58.03 µM). Furthermore, cell cycle and apoptosis analyses described that compound 3 prompts the G1 phase arrest in michigan cancer foundation-7 cancer cells and increases the apoptosis ratio by 29.31% with respect to untreated cells (2.25%). Additionally, the conducted molecular docking assured the promising binding of the investigated members toward Topo I and II with potential DNA intercalation. Accordingly, the synthesized compounds could be treated as promising anticancer candidates for future optimization.
研究人员设计并合成了一系列四氢苯并[b]噻吩衍生物,作为拓扑异构酶(Topo)I/II 的双重抑制剂,具有潜在的 DNA 插层作用。2- 氨基-3-氰基-4,5,6,7-四氢苯并[b]噻吩-4-羧酸乙酯(1)是通过使用 Fe2O3 纳米催化剂修改 Gewald 反应程序制备的,然后将其作为合成四氢苯并[b]噻吩候选化合物(2-14)的构件。有趣的是,化合物 14 对肝癌、结直肠癌和乳腺癌细胞株显示出最佳的细胞毒性潜力(IC50 = 7.79、8.10 和 3.53 µM),超过了多柔比星对乳腺癌的作用(IC50 = 4.17 µM)。同时,Topo I 和 II 抑制试验显示,与作为参考标准的喜树碱(IC50 = 28.34 nM)和多柔比星(IC50 = 11.01 nM)相比,化合物 3 在候选化合物中表现出最佳的抑制潜力(IC50 = 25.26 和 10.01 nM)。此外,DNA 插层试验表明,与多柔比星(IC50 = 58.03 µM)相比,化合物 14 的结合亲和力最佳,IC50 值为 77.82 µM。此外,细胞周期和细胞凋亡分析表明,与未处理的细胞(2.25%)相比,化合物 3 能促使密歇根癌症基金会-7 癌细胞的 G1 期停滞,并使细胞凋亡率增加 29.31%。此外,进行的分子对接证明,所研究的成员有望与 Topo I 和 Topo II 结合,并具有潜在的 DNA 插层作用。因此,合成的化合物可作为有希望的抗癌候选化合物,供未来优化之用。
{"title":"Pharmacophore-based, rationale design, and efficient synthesis of novel tetrahydrobenzo[b]thiophene candidates as potential dual Topo I/II inhibitors and DNA intercalators","authors":"Hager R. Nofal, Ahmed A. Al-Karmalawy, Ayman Abo Elmaaty, Mahmoud F. Ismail, Ali Khalil Ali, Eslam M. Abbass","doi":"10.1002/ardp.202400217","DOIUrl":"10.1002/ardp.202400217","url":null,"abstract":"<p>A series of tetrahydrobenzo[<i>b</i>]thiophene derivatives was designed and synthesized as dual topoisomerase (Topo) I/II inhibitors implicating potential DNA intercalation. Ethyl-2-amino-3-cyano-4,5,6,7-tetrahydrobenzo[<i>b</i>]thiophene-4-carboxylate (<b>1</b>) was prepared by modification of the Gewald reaction procedure using a Fe<sub>2</sub>O<sub>3</sub> nanocatalyst and then it was used as a building block for the synthesis of tetrahydrobenzo[<i>b</i>]thiophene candidates (<b>2–14</b>). Interestingly, compound <b>14</b> showed the best cytotoxic potential against hepatocellular, colorectal, and breast cancer cell lines (IC<sub>50</sub> = 7.79, 8.10, and 3.53 µM), respectively, surpassing doxorubicin at breast cancer (IC<sub>50</sub> = 4.17 µM). Meanwhile, the Topo I and II inhibition assay displayed that compound <b>3</b> could exhibit the best inhibitory potential among the investigated candidates (IC<sub>50</sub> = 25.26 and 10.01 nM), respectively, in comparison to camptothecin (IC<sub>50</sub> = 28.34 nM) and doxorubicin (IC<sub>50</sub> = 11.01 nM), as reference standards. In addition, the DNA intercalation assay showed that compound <b>14</b> could display the best binding affinity with an IC<sub>50</sub> value of 77.82 µM in comparison to doxorubicin (IC<sub>50</sub> = 58.03 µM). Furthermore, cell cycle and apoptosis analyses described that compound <b>3</b> prompts the G1 phase arrest in michigan cancer foundation-7 cancer cells and increases the apoptosis ratio by 29.31% with respect to untreated cells (2.25%). Additionally, the conducted molecular docking assured the promising binding of the investigated members toward Topo I and II with potential DNA intercalation. Accordingly, the synthesized compounds could be treated as promising anticancer candidates for future optimization.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141304945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Irina Lazarova, Nilofar, Giovanni Caprioli, Diletta Piatti, Massimo Ricciutelli, Musa Denizhan Ulusan, Ismail Koyuncu, Ozgur Yuksekdag, Adriano Mollica, Azzurra Stefanucci, Gokhan Zengin
The n-hexane, ethyl acetate, ethanol, ethanol/water (70% ethanol), and water extracts of Astragalus aduncus aerial parts were investigated for their antioxidant potential, enzyme inhibition activity (anti-acetylcholinesterase [AChE], anti-butyrylcholinesterase [BChE], antityrosinase, antiamylase, and antiglucosidase) and antiproliferative effect (against colon adenocarcinoma cell line [HT-29], gastric cancer cell line [HGC-27], prostate carcinoma cell line [DU-145], breast adenocarcinoma cell line [MDA-MB-231], and cervix adenocarcinoma cell line [HeLa]). In addition, the phytochemical profile of the extracts was evaluated using validated spectrophotometric and high-pressure liquid chromatography-electrospray ionization/tandem mass spectroscopy methods. Generally, the 70% ethanol extract demonstrated the strongest antioxidant properties, and it was the richest source of total phenolic constituents. Our findings indicated that the ethyl acetate extract was the most potent BChE inhibitor (11.44 mg galantamine equivalents [GALAE]/g) followed by the ethanol extract (8.51 mg GALAE/g), while the ethanol extract was the most promising AChE inhibitor (3.42 mg GALAE/g) followed by the ethanol/water extract (3.17 mg GALAE/g). Excellent tyrosinase inhibitory activity (66.25 mg kojic acid equivalent/g) was observed in ethanol/water extracts of the aerial part of A. aduncus. Тhese results showed that the most cytotoxic effects were exhibited by the ethyl acetate extract against HGC-27 cells (IC50: 36.76 µg/mL), the ethanol extract against HT-29 cells (IC50: 30.79 µg/mL), and the water extract against DU-145 cells (IC50: 37.01 µg/mL). A strong correlation was observed between the highest total flavonoid content and the highest content of individual compounds in the ethanol extract, including rutin, hyperoside, isoquercitrin, delphinidin-3,5-diglucoside (delphinidin-3,5-O-diglucoside), and kaempferol-3-glucoside (kaempferol-3-O-glucoside). In the present study, the A. aduncus plant was considered a new source of antioxidants, enzyme inhibitors, and anticancer agents and could be used as a future health-benefit natural product.
{"title":"Influence of extraction solvents on the chemical constituents and biological activities of Astragalus aduncus from Turkey flora: In vitro and in silico insights","authors":"Irina Lazarova, Nilofar, Giovanni Caprioli, Diletta Piatti, Massimo Ricciutelli, Musa Denizhan Ulusan, Ismail Koyuncu, Ozgur Yuksekdag, Adriano Mollica, Azzurra Stefanucci, Gokhan Zengin","doi":"10.1002/ardp.202400257","DOIUrl":"10.1002/ardp.202400257","url":null,"abstract":"<p>The <i>n</i>-hexane, ethyl acetate, ethanol, ethanol/water (70% ethanol), and water extracts of <i>Astragalus aduncus</i> aerial parts were investigated for their antioxidant potential, enzyme inhibition activity (anti-acetylcholinesterase [AChE], anti-butyrylcholinesterase [BChE], antityrosinase, antiamylase, and antiglucosidase) and antiproliferative effect (against colon adenocarcinoma cell line [HT-29], gastric cancer cell line [HGC-27], prostate carcinoma cell line [DU-145], breast adenocarcinoma cell line [MDA-MB-231], and cervix adenocarcinoma cell line [HeLa]). In addition, the phytochemical profile of the extracts was evaluated using validated spectrophotometric and high-pressure liquid chromatography-electrospray ionization/tandem mass spectroscopy methods. Generally, the 70% ethanol extract demonstrated the strongest antioxidant properties, and it was the richest source of total phenolic constituents. Our findings indicated that the ethyl acetate extract was the most potent BChE inhibitor (11.44 mg galantamine equivalents [GALAE]/g) followed by the ethanol extract (8.51 mg GALAE/g), while the ethanol extract was the most promising AChE inhibitor (3.42 mg GALAE/g) followed by the ethanol/water extract (3.17 mg GALAE/g). Excellent tyrosinase inhibitory activity (66.25 mg kojic acid equivalent/g) was observed in ethanol/water extracts of the aerial part of <i>A</i>. <i>aduncus</i>. Тhese results showed that the most cytotoxic effects were exhibited by the ethyl acetate extract against HGC-27 cells (IC<sub>50</sub>: 36.76 µg/mL), the ethanol extract against HT-29 cells (IC<sub>50</sub>: 30.79 µg/mL), and the water extract against DU-145 cells (IC<sub>50</sub>: 37.01 µg/mL). A strong correlation was observed between the highest total flavonoid content and the highest content of individual compounds in the ethanol extract, including rutin, hyperoside, isoquercitrin, delphinidin-3,5-diglucoside (delphinidin-3,5-<i>O</i>-diglucoside), and kaempferol-3-glucoside (kaempferol-3-<i>O</i>-glucoside). In the present study, the <i>A. aduncus</i> plant was considered a new source of antioxidants, enzyme inhibitors, and anticancer agents and could be used as a future health-benefit natural product.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141287455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Scutellarein is a flavonoid from Scutellaria baicalensis Georgi that has been shown to have a variety of pharmacological activities. This review aims to summarize the pharmacological and pharmacokinetic studies on scutellarein and provide useful information for relevant scholars. Pharmacological studies indicate that scutellarein possesses a diverse range of pharmacological properties, including but not limited to anti-inflammatory, antioxidant, antiviral, neuroprotective, hypoglycemic, hypolipidemic, anticancer, and cardiovascular protective effects. Further investigation reveals that the pharmacological effects of scutellarein are driven by multiple mechanisms. These mechanisms encompass the scavenging of free radicals, inhibition of the activation of inflammatory signaling pathways and expression of inflammatory mediators, inhibition of the activity of crucial viral proteins, suppression of gluconeogenesis, amelioration of insulin resistance, improvement of cerebral ischemia-reperfusion injury, induction of apoptosis in cancer cells, and prevention of myocardial hypertrophy, among others. In summary, these pharmacological studies suggest that scutellarein holds promise for the treatment of various diseases. It is imperative to conduct clinical studies to further elucidate the therapeutic effects of scutellarein. However, it is worth noting that studies on the pharmacokinetics reveal an inhibitory effect of scutellarein on uridine 5′-diphosphate glucuronide transferases and cytochrome P450 enzymes, potentially posing safety risks.
{"title":"Review on the pharmacological effects and pharmacokinetics of scutellarein","authors":"Jiang Lai, Chunxiao Li","doi":"10.1002/ardp.202400053","DOIUrl":"10.1002/ardp.202400053","url":null,"abstract":"<p>Scutellarein is a flavonoid from <i>Scutellaria baicalensis </i><span>Georgi</span> that has been shown to have a variety of pharmacological activities. This review aims to summarize the pharmacological and pharmacokinetic studies on scutellarein and provide useful information for relevant scholars. Pharmacological studies indicate that scutellarein possesses a diverse range of pharmacological properties, including but not limited to anti-inflammatory, antioxidant, antiviral, neuroprotective, hypoglycemic, hypolipidemic, anticancer, and cardiovascular protective effects. Further investigation reveals that the pharmacological effects of scutellarein are driven by multiple mechanisms. These mechanisms encompass the scavenging of free radicals, inhibition of the activation of inflammatory signaling pathways and expression of inflammatory mediators, inhibition of the activity of crucial viral proteins, suppression of gluconeogenesis, amelioration of insulin resistance, improvement of cerebral ischemia-reperfusion injury, induction of apoptosis in cancer cells, and prevention of myocardial hypertrophy, among others. In summary, these pharmacological studies suggest that scutellarein holds promise for the treatment of various diseases. It is imperative to conduct clinical studies to further elucidate the therapeutic effects of scutellarein. However, it is worth noting that studies on the pharmacokinetics reveal an inhibitory effect of scutellarein on uridine 5′-diphosphate glucuronide transferases and cytochrome P450 enzymes, potentially posing safety risks.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141287456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
It is generally believed that the main influencing factors of plant metabolism are genetic and environmental factors. However, the transformation and catalysis of metabolic intermediates by endophytic fungi have become a new factor and resource attracting attention in recent years. There are over 2000 precious plant species in the Astragalus genus. In the past decade, at least 303 high-value metabolites have been isolated from the Astragalus medicinal plants, including 124 saponins, 150 flavonoids, two alkaloids, six sterols, and over 20 other types of compounds. These medicinal plants contain abundant endophytic fungi with unique functions, and nearly 600 endophytic fungi with known identity have been detected, but only about 35 strains belonging to 13 genera have been isolated. Among them, at least four strains affiliated to Penicillium roseopurpureum, Alternaria eureka, Neosartorya hiratsukae, and Camarosporium laburnicola have demonstrated the ability to biotransform four saponin compounds from the Astragalus genus, resulting in the production of 66 new compounds, which have significantly enhanced our understanding of the formation of metabolites in plants of the Astragalus genus. They provide a scientific basis for improving the cultivation quality of Astragalus plants through the modification of dominant fungal endophytes or reshaping the endophytic fungal community. Additionally, they open up new avenues for the discovery of specialized, green, efficient, and sustainable biotransformation pathways for complex pharmaceutical intermediates.
{"title":"Progress on metabolites of Astragalus medicinal plants and a new factor affecting their formation: Biotransformation of endophytic fungi","authors":"Ding-Hui Feng, Jin-Long Cui","doi":"10.1002/ardp.202400249","DOIUrl":"10.1002/ardp.202400249","url":null,"abstract":"<p>It is generally believed that the main influencing factors of plant metabolism are genetic and environmental factors. However, the transformation and catalysis of metabolic intermediates by endophytic fungi have become a new factor and resource attracting attention in recent years. There are over 2000 precious plant species in the <i>Astragalus</i> genus. In the past decade, at least 303 high-value metabolites have been isolated from the <i>Astragalus</i> medicinal plants, including 124 saponins, 150 flavonoids, two alkaloids, six sterols, and over 20 other types of compounds. These medicinal plants contain abundant endophytic fungi with unique functions, and nearly 600 endophytic fungi with known identity have been detected, but only about 35 strains belonging to 13 genera have been isolated. Among them, at least four strains affiliated to <i>Penicillium roseopurpureum</i>, <i>Alternaria eureka</i>, <i>Neosartorya hiratsukae</i>, and <i>Camarosporium laburnicola</i> have demonstrated the ability to biotransform four saponin compounds from the <i>Astragalus</i> genus, resulting in the production of 66 new compounds, which have significantly enhanced our understanding of the formation of metabolites in plants of the <i>Astragalus</i> genus. They provide a scientific basis for improving the cultivation quality of <i>Astragalus</i> plants through the modification of dominant fungal endophytes or reshaping the endophytic fungal community. Additionally, they open up new avenues for the discovery of specialized, green, efficient, and sustainable biotransformation pathways for complex pharmaceutical intermediates.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141260148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Özcan Güleç, Ahmet T. Bilgiçli, Burak Tüzün, Parham Taslimi, Armağan Günsel, İlhami Gülçin, Mustafa Arslan, M. Nilüfer Yarasir
In this study, (E)-4-{4-[(1-oxo-3,4-dihydronaphthalen-2(1H)-ylidene)methyl]phenoxy}phthalonitrile (4) and its phthalocyanine derivatives (5–8) were synthesized for the first time. Aggregation behaviors of the novel soluble phthalocyanines in organic solvents were investigated. In addition, the efficiency of 1O2 production of (5) and ZnPc (6) was investigated. The singlet oxygen quantum yields (ΦΔ) for 2HPc (5) and ZnPc (6) were found to be 0.58 and 0.83, respectively. Additionally, novel phthalocyanines (5–8) were investigated for their ability to inhibit enzymes. They exhibited a highly potent inhibition effect on human carbonic anhydrase I and II (hCA I and II) and α-glycosidase (α-Gly) enzymes. Ki values are in the range of 2.60 ± 9.87 to 11.53 ± 6.92 µM, 3.35 ± 0.53 to 15.47 ± 1.20 µM, and 28.60 ± 4.82 to 40.58 ± 7.37 nM, respectively. The calculations of the studied molecule at the B3LYP, HF, and M062X levels in the 6–31G basis sets were made using the Gaussian package program. Afterward, the interactions occurring in the docking calculation against a protein that is the crystal structure of hCA I (PDB ID: 2CAB), the crystal structure of hCA II (PDB ID: 5AML), and the crystal structure of α-Gly (PDB ID: 1R47), were examined. Following that, Protein–Ligand Interaction Profiler (PLIP) analysis was used to look at the interactions that occurred during the docking calculation in further detail.
{"title":"Peripheral (E)-2-[(4-hydroxybenzylidene)-3,4-dihydronaphthalen-1(2H)-one)]-coordinated phthalocyanines with improved enzyme inhibition properties and photophysicochemical behaviors","authors":"Özcan Güleç, Ahmet T. Bilgiçli, Burak Tüzün, Parham Taslimi, Armağan Günsel, İlhami Gülçin, Mustafa Arslan, M. Nilüfer Yarasir","doi":"10.1002/ardp.202400209","DOIUrl":"10.1002/ardp.202400209","url":null,"abstract":"<p>In this study, (<i>E</i>)-4-{4-[(1-oxo-3,4-dihydronaphthalen-2(1<i>H</i>)-ylidene)methyl]phenoxy}phthalonitrile (<b>4</b>) and its phthalocyanine derivatives (<b>5–8</b>) were synthesized for the first time. Aggregation behaviors of the novel soluble phthalocyanines in organic solvents were investigated. In addition, the efficiency of <sup>1</sup>O<sub>2</sub> production of (<b>5</b>) and ZnPc (<b>6</b>) was investigated. The singlet oxygen quantum yields (Φ<sub>Δ</sub>) for 2HPc (<b>5</b>) and ZnPc (<b>6</b>) were found to be 0.58 and 0.83, respectively. Additionally, novel phthalocyanines (<b>5–8</b>) were investigated for their ability to inhibit enzymes. They exhibited a highly potent inhibition effect on human carbonic anhydrase I and II (hCA I and II) and α-glycosidase (α-Gly) enzymes. <i>K</i><sub>i</sub> values are in the range of 2.60 ± 9.87 to 11.53 ± 6.92 µM, 3.35 ± 0.53 to 15.47 ± 1.20 µM, and 28.60 ± 4.82 to 40.58 ± 7.37 nM, respectively. The calculations of the studied molecule at the B3LYP, HF, and M062X levels in the 6–31G basis sets were made using the Gaussian package program. Afterward, the interactions occurring in the docking calculation against a protein that is the crystal structure of hCA I (PDB ID: 2CAB), the crystal structure of hCA II (PDB ID: 5AML), and the crystal structure of α-Gly (PDB ID: 1R47), were examined. Following that, Protein–Ligand Interaction Profiler (PLIP) analysis was used to look at the interactions that occurred during the docking calculation in further detail.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.202400209","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141260145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pranali Vijaykumar Kuthe, Mohammad Muzaffar-Ur-Rehman, Ala Chandu, Kirad Shivani Prashant, Murugesan Sankarnarayanan
Plasmodium parasites are the primary cause of malaria, leading to high mortality rates, which require clinical attention. Many of the medications used in the treatment have resulted in resistance over time. Artemisinin combination therapy (ACT) has shown significant results for the treatment. However, mutations in the parasite have resulted in resistance, leading to decreased efficiency of the medications that are currently being used. Therefore, there is a critical need to find novel scaffolds that are safe, effective, and of economic advantage. Literature has reported several potent molecules with diverse scaffolds designed, synthesized, and evaluated against different strains of Plasmodium. With this growing list of compounds, it is essential to collect the data in one place to gain a concise overview of the emerging scaffolds in recent years. For this purpose, nitrogen-containing heterocycles such as β-carboline, imidazole, quinazoline, quinoline, thiazole, and thiophene have been highly explored due to their wide biological applications. Besides these, another scaffold, benzodiazepine, which is majorly used as a central nervous system depressant, is emerging as an anti-malarial agent. Hence, this review centers on the latest medication advancements designed to combat malaria, emphasizing special attention to 1,4-benzodiazepines as a novel scaffold for antimalarial drug discovery.
{"title":"Unlocking nitrogen compounds’ promise against malaria: A comprehensive review","authors":"Pranali Vijaykumar Kuthe, Mohammad Muzaffar-Ur-Rehman, Ala Chandu, Kirad Shivani Prashant, Murugesan Sankarnarayanan","doi":"10.1002/ardp.202400222","DOIUrl":"10.1002/ardp.202400222","url":null,"abstract":"<p><i>Plasmodium</i> parasites are the primary cause of malaria, leading to high mortality rates, which require clinical attention. Many of the medications used in the treatment have resulted in resistance over time. Artemisinin combination therapy (ACT) has shown significant results for the treatment. However, mutations in the parasite have resulted in resistance, leading to decreased efficiency of the medications that are currently being used. Therefore, there is a critical need to find novel scaffolds that are safe, effective, and of economic advantage. Literature has reported several potent molecules with diverse scaffolds designed, synthesized, and evaluated against different strains of <i>Plasmodium</i>. With this growing list of compounds, it is essential to collect the data in one place to gain a concise overview of the emerging scaffolds in recent years. For this purpose, nitrogen-containing heterocycles such as β-carboline, imidazole, quinazoline, quinoline, thiazole, and thiophene have been highly explored due to their wide biological applications. Besides these, another scaffold, benzodiazepine, which is majorly used as a central nervous system depressant, is emerging as an anti-malarial agent. Hence, this review centers on the latest medication advancements designed to combat malaria, emphasizing special attention to 1,4-benzodiazepines as a novel scaffold for antimalarial drug discovery.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141260151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}