The Sceletium-type alkaloids, known for their anxiolytic and antidepressant activities, have been recently found to be biosynthesized in Narcissus cv. Hawera, which is largely used as an ornamental plant. An alkaloid fraction enriched with Sceletium-type alkaloids from the plant has shown promising antidepressant and anxiolytic activities. In the present study, qualitative and quantitative analyses of the alkaloids in the plant organs were performed during one vegetation season by GC-MS. The alkaloid pattern and total alkaloid content was found to depend strongly on the stage of development and plant organ. The alkaloid content of bulbs was found to be highest during the dormancy period and lowest in sprouting bulbs. The leaves showed the highest alkaloid content during the intensive vegetative growth and lowest during flowering. In total, 13 alkaloids were detected in the methanol extracts of Narcissus cv. Hawera, six Sceletium-type and seven typical Amaryllidaceae alkaloids. Major alkaloids in the alkaloid pattern were lycorine, 6-epi-mesembrenol, mesembrenone, sanguinine, and galanthamine. The leaves of flowering plants were found to have the highest amount of 6-epi-mesembrenol. Mesembrenone was found to be dominant alkaloid in the leaves of sprouting bulbs and in the flowers. Considering the biomass of the plant, the dormant bulbs are the best source of alkaloid fractions enriched with 6-epi-mesembrenol. The flowers and the young leaves can be used for preparation of alkaloid fractions enriched with mesembrenone. The results indicates that Narcissus cv. Hawera is an emerging source of valuable bioactive compounds and its utilization can be extended as a medicinal plant.
{"title":"Dynamics of alkaloid accumulation in <i>Narcissus</i> cv. Hawera: a source of <i>Sceletium</i>-type alkaloids.","authors":"Borjana Sidjimova, Rumen Denev, Milena Nikolova, Jaume Bastida, Strahil Berkov","doi":"10.1515/znc-2023-0149","DOIUrl":"10.1515/znc-2023-0149","url":null,"abstract":"<p><p>The <i>Sceletium</i>-type alkaloids, known for their anxiolytic and antidepressant activities, have been recently found to be biosynthesized in <i>Narcissus</i> cv. Hawera, which is largely used as an ornamental plant. An alkaloid fraction enriched with <i>Sceletium</i>-type alkaloids from the plant has shown promising antidepressant and anxiolytic activities. In the present study, qualitative and quantitative analyses of the alkaloids in the plant organs were performed during one vegetation season by GC-MS. The alkaloid pattern and total alkaloid content was found to depend strongly on the stage of development and plant organ. The alkaloid content of bulbs was found to be highest during the dormancy period and lowest in sprouting bulbs. The leaves showed the highest alkaloid content during the intensive vegetative growth and lowest during flowering. In total, 13 alkaloids were detected in the methanol extracts of <i>Narcissus</i> cv. Hawera, six <i>Sceletium</i>-type and seven typical Amaryllidaceae alkaloids. Major alkaloids in the alkaloid pattern were lycorine, 6-<i>epi</i>-mesembrenol, mesembrenone, sanguinine, and galanthamine. The leaves of flowering plants were found to have the highest amount of 6-<i>epi</i>-mesembrenol. Mesembrenone was found to be dominant alkaloid in the leaves of sprouting bulbs and in the flowers. Considering the biomass of the plant, the dormant bulbs are the best source of alkaloid fractions enriched with 6-<i>epi</i>-mesembrenol. The flowers and the young leaves can be used for preparation of alkaloid fractions enriched with mesembrenone. The results indicates that <i>Narcissus</i> cv. Hawera is an emerging source of valuable bioactive compounds and its utilization can be extended as a medicinal plant.</p>","PeriodicalId":49344,"journal":{"name":"Zeitschrift Fur Naturforschung Section C-A Journal of Biosciences","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140186135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-21Print Date: 2024-03-25DOI: 10.1515/znc-2024-0004
Mohamed Shaaban, Mohamed A Ghani
Soft corals, particularly Sarcophyton sp. are rich in metabolites with variety of biological activities. In this study, a pyran-based 9-exo-methylene-10-hydroxy-sarcotrocheliol (1) and 2-dehydro-4-peroxy-sarcophine (2), two new cembranoide diterpenes, were isolated together with 9-hydroxy-10,11-dehydro-sarcotrocheliol, sarcotrocheliol, sarcotrocheliol acetate, sarcophine, (+)-7α,8β-dihydroxydeepoxysarcophine, (±)-sarcophytonine B, and peridinin from the organic extract of Sarcophyton glaucum collected at the coasts of Hurghada, Egypt. The structures of the new diterpenes 1-2 were identified based on cumulative analyses of HRESIMS and NMR (1D/2D NMR) spectra. The relative configurations of both compounds were verified by NOESY spectra and comparison with our recently reported analogues. The compounds showed no antimicrobial activity against a set of diverse tested microorganisms.
{"title":"Pyrane-based cembranoid and 2-dehydro-4-peroxy-sarcophine: two new diterpenes from <i>Sarcophyton glaucum</i>.","authors":"Mohamed Shaaban, Mohamed A Ghani","doi":"10.1515/znc-2024-0004","DOIUrl":"10.1515/znc-2024-0004","url":null,"abstract":"<p><p>Soft corals, particularly <i>Sarcophyton</i> sp. are rich in metabolites with variety of biological activities. In this study, a pyran-based 9-<i>exo</i>-methylene-10-hydroxy-sarcotrocheliol (<b>1</b>) and 2-dehydro-4-peroxy-sarcophine (<b>2</b>), two new cembranoide diterpenes, were isolated together with 9-hydroxy-10,11-dehydro-sarcotrocheliol, sarcotrocheliol, sarcotrocheliol acetate, sarcophine, (+)-7<i>α</i>,8<i>β</i>-dihydroxydeepoxysarcophine, (±)-sarcophytonine B, and peridinin from the organic extract of <i>Sarcophyton glaucum</i> collected at the coasts of Hurghada, Egypt. The structures of the new diterpenes <b>1-2</b> were identified based on cumulative analyses of HRESIMS and NMR (1D/2D NMR) spectra. The relative configurations of both compounds were verified by NOESY spectra and comparison with our recently reported analogues. The compounds showed no antimicrobial activity against a set of diverse tested microorganisms.</p>","PeriodicalId":49344,"journal":{"name":"Zeitschrift Fur Naturforschung Section C-A Journal of Biosciences","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140177396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Many disorders, including cancer and malaria, could be targeted via the pentose phosphate pathway (PPP), whose products are key in biosynthetic reactions in cells. The goal of this study was to find new PPP inhibitors. The inhibition effects of malononitrile derivatives on Glucose 6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) were analyzed through in vitro experiments. Besides, molecular docking studies were performed to predict the interactions having role in inhibition of compounds. Ki constants of derivatives were found between 4.24 ± 0.46-69.63 ± 7.75 µM for G6PD and 1.91 ± 0.12-95.07 ± 11.08 µM for 6PGD. Derivatives indicated non-competitive inhibition on both enzymes except for compound 4. The findings of the molecular docking studies revealed that free-binding energy estimations agreed with in vitro data. The structure of these malononitrile derivatives may guide for drug discovery in targeting the PPP.
包括癌症和疟疾在内的许多疾病都可以通过磷酸戊糖途径(PPP)来治疗,该途径的产物是细胞内生物合成反应的关键。这项研究的目的是寻找新的磷酸戊糖途径抑制剂。通过体外实验分析了丙二腈衍生物对 6-磷酸葡萄糖脱氢酶(G6PD)和 6-磷酸葡萄糖酸脱氢酶(6PGD)的抑制作用。此外,还进行了分子对接研究,以预测化合物在抑制作用中的相互作用。发现衍生物对 G6PD 的 K i 常数在 4.24 ± 0.46-69.63 ± 7.75 µM 之间,对 6PGD 的 K i 常数在 1.91 ± 0.12-95.07 ± 11.08 µM 之间。除化合物 4 外,其他衍生物对这两种酶都有非竞争性抑制作用。分子对接研究结果表明,自由结合能估计值与体外数据一致。这些丙二腈衍生物的结构可为靶向 PPP 的药物发现提供指导。
{"title":"<i>In vitro</i> inhibition potency of malononitrile derivatives on the activity of two pentose phosphate pathway enzymes: accompanied by molecular docking evaluation.","authors":"Arzu Öztürk Kesebir, Ziya Dağalan, Pınar Güller, Bilal Nişancı, Ömer İrfan Küfrevioğlu","doi":"10.1515/znc-2023-0164","DOIUrl":"https://doi.org/10.1515/znc-2023-0164","url":null,"abstract":"<p><p>Many disorders, including cancer and malaria, could be targeted via the pentose phosphate pathway (PPP), whose products are key in biosynthetic reactions in cells. The goal of this study was to find new PPP inhibitors. The inhibition effects of malononitrile derivatives on Glucose 6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) were analyzed through <i>in vitro</i> experiments. Besides, molecular docking studies were performed to predict the interactions having role in inhibition of compounds. <i>K</i> <sub>i</sub> constants of derivatives were found between 4.24 ± 0.46-69.63 ± 7.75 µM for G6PD and 1.91 ± 0.12-95.07 ± 11.08 µM for 6PGD. Derivatives indicated non-competitive inhibition on both enzymes except for compound <b>4.</b> The findings of the molecular docking studies revealed that free-binding energy estimations agreed with <i>in vitro</i> data. The structure of these malononitrile derivatives may guide for drug discovery in targeting the PPP.</p>","PeriodicalId":49344,"journal":{"name":"Zeitschrift Fur Naturforschung Section C-A Journal of Biosciences","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140144448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-14Print Date: 2024-05-27DOI: 10.1515/znc-2023-0148
Harika Atmaca, Ferdi Oguz, Suleyman Ilhan
Although chemotherapy is still the most preferred treatment for cancer, most chemotherapeutic agents target both cancer cells and healthy cells and cause serious side effects due to high toxicity. Improved drug delivery systems (DDSs), which enhance the efficacy of current chemotherapeutic drugs while reducing their toxicity, offer potential solutions to these challenges. Chitosan (CS) and its derivatives are biopolymers with biodegradable, biocompatible, and low-toxicity properties, and their structure allows for convenient chemical and mechanical modifications. In its role as a therapeutic agent, CS can impede the proliferation of tumor cells through the inhibition of angiogenesis and metastasis, as well as by triggering apoptosis. CS and its derivatives are also frequently preferred as DDSs due to their properties such as high drug-carrying capacity, polycationic structure, long-term circulation, and direct targeting of cancer cells. Various therapeutic agents linked to CS and its derivatives demonstrate potent anticancer effects with advantages such as reduced side effects compared to the original drugs, owing to factors like targeted distribution within cancer tissues and sustained release. This review emphasizes the utilization of CS and its derivatives, both as therapeutic agents and as carriers for established chemotherapeutic drugs.
{"title":"Chitosan in cancer therapy: a dual role as a therapeutic agent and drug delivery system.","authors":"Harika Atmaca, Ferdi Oguz, Suleyman Ilhan","doi":"10.1515/znc-2023-0148","DOIUrl":"10.1515/znc-2023-0148","url":null,"abstract":"<p><p>Although chemotherapy is still the most preferred treatment for cancer, most chemotherapeutic agents target both cancer cells and healthy cells and cause serious side effects due to high toxicity. Improved drug delivery systems (DDSs), which enhance the efficacy of current chemotherapeutic drugs while reducing their toxicity, offer potential solutions to these challenges. Chitosan (CS) and its derivatives are biopolymers with biodegradable, biocompatible, and low-toxicity properties, and their structure allows for convenient chemical and mechanical modifications. In its role as a therapeutic agent, CS can impede the proliferation of tumor cells through the inhibition of angiogenesis and metastasis, as well as by triggering apoptosis. CS and its derivatives are also frequently preferred as DDSs due to their properties such as high drug-carrying capacity, polycationic structure, long-term circulation, and direct targeting of cancer cells. Various therapeutic agents linked to CS and its derivatives demonstrate potent anticancer effects with advantages such as reduced side effects compared to the original drugs, owing to factors like targeted distribution within cancer tissues and sustained release. This review emphasizes the utilization of CS and its derivatives, both as therapeutic agents and as carriers for established chemotherapeutic drugs.</p>","PeriodicalId":49344,"journal":{"name":"Zeitschrift Fur Naturforschung Section C-A Journal of Biosciences","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140121199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A novel isocoumarin was isolated from the mycelia of the dark septate endophytic fungus Phialocephala fortinii. The chemical structure was determined to be 8-hydroxy-6-methoxy-3,7-dimethyl-1H-2-benzopyran-1-one based on mass spectrometry, 1H-nuclear magnetic resonance (NMR), and 13C-NMR spectroscopic analyses, including 2D-NMR experiments. The isolated compound inhibited root growth of Arabidopsis thaliana, suggesting its potential as a plant growth regulator.
{"title":"Isolation, structural elucidation, and biological activity of a novel isocoumarin from the dark septate endophytic fungus <i>Phialocephala fortinii</i>.","authors":"Kei Bando, Ryoga Kushibe, Naoki Kitaoka, Yutaka Tamai, Kazuhiko Narisawa, Hideyuki Matsuura","doi":"10.1515/znc-2023-0139","DOIUrl":"10.1515/znc-2023-0139","url":null,"abstract":"<p><p>A novel isocoumarin was isolated from the mycelia of the dark septate endophytic fungus <i>Phialocephala fortinii</i>. The chemical structure was determined to be 8-hydroxy-6-methoxy-3,7-dimethyl-1<i>H</i>-2-benzopyran-1-one based on mass spectrometry, <sup>1</sup>H-nuclear magnetic resonance (NMR), and <sup>13</sup>C-NMR spectroscopic analyses, including 2D-NMR experiments. The isolated compound inhibited root growth of <i>Arabidopsis thaliana</i>, suggesting its potential as a plant growth regulator.</p>","PeriodicalId":49344,"journal":{"name":"Zeitschrift Fur Naturforschung Section C-A Journal of Biosciences","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139991640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-29Print Date: 2024-01-29DOI: 10.1515/znc-2023-0157
Getachew Tegegn, Yadessa Melaku, Muhdin Aliye, Abiy Abebe, Negera Abdissa, Asfaw Meresa, Sileshi Degu, Mo Hunsen, Ahmed A Hussein, Milkyas Endale
Verbascum sinaiticum is locally used to treat wound, stomachache, viral infection, cancer, sunstroke fever, abdominal colic, diarrhea, hemorrhage, anthrax, and hepatitis. The objective of this study was to identify the compounds and to evaluate the antimicrobial and antioxidant activity of the extracts and isolated compounds from V. sinaiticum. The 1H-NMR, 13C-NMR, and DEPT-135 were used to elucidate the structures of isolated compounds. Essential oils were extracted by hydrodistillation method and their chemical analyses were performed by GC-MS. The broth microdilution method was used to evaluate the antimicrobial activity. The radical scavenging activity of the extracts and isolated compounds were evaluated using DPPH method. Silica gel column chromatographic separation of root extracts afforded seven known compounds: 3'-(4''-methoxy phenyl)-3'-oxo-propionyl hexadecanoate (1), harpagoside (2), pulverulentoside I (3), scrophuloside B4 (4), scropolioside A (5), scropolioside-D2 (6), and harpagide 6-O-β-glucoside (7), which are all reported from this species for the first time. The EO extracts from leaves and roots were the most susceptible to Streptococcus agalactiae, with a 2 mg/mL MIC. The EO from roots was effective against Candida albicans and Trichophyton mentagrophytes, with a MIC of 8 mg/mL. The MeOH and CH2Cl2/CH3OH (1:1) root extracts showed the maximum activity against S. epidermidis with MIC values of 0.25 mg/mL. The strongest antibacterial effects were demonstrated against Staphylococcus epidermidis, which exhibited a 0.0625 mg/mL MIC for compound 1. The strongest radical scavenging activity was exhibited by the methanol extract (IC50 = 3.4 μg/mL), and compounds 4, 6, 5, 3, 7, and 2 with IC50 values of 3.2, 3.38, 3.6, 3.8, 4.2, and 4.7 μg/mL, respectively, in comparison with ascorbic acid (IC50 = 1.3 μg/mL). The results of the molecular docking analysis of compounds revealed minimal binding energies range from -38.5 to -43.1 kJ/mol, -33.1 to -42.7 kJ/mol, -34.7 to -39.3.7 kJ/mol, -25.5 to -37.6 kJ/mol against human myeloperoxidase (PDB ID: 1DNU), murA enzyme (PDB ID: 1UAE), human topoisomerase IIβ (PDB ID: 4fm9), S. epidermidis FtsZ (PDB number: 4M8I) proteins, respectively. The docking results and the in vitro antibacterial activity are in good agreement. These findings show that the isolated compounds 2-7 can act as potential antioxidants and strong antibacterials against Staphylococcus aureus and S. epidermidis. As a result, V. sinaiticum root extracts have the potential to be effective in treating diseases caused by bacteria and free radicals, as long as further investigation has been suggested for the ultimate decision of this plan
{"title":"<i>In vitro</i> antimicrobial and antioxidant activities, essential oil composition, and <i>in silico</i> molecular modeling analysis of secondary metabolites from roots of <i>Verbascum sinaiticum</i>.","authors":"Getachew Tegegn, Yadessa Melaku, Muhdin Aliye, Abiy Abebe, Negera Abdissa, Asfaw Meresa, Sileshi Degu, Mo Hunsen, Ahmed A Hussein, Milkyas Endale","doi":"10.1515/znc-2023-0157","DOIUrl":"10.1515/znc-2023-0157","url":null,"abstract":"<p><p><i>Verbascum sinaiticum</i> is locally used to treat wound, stomachache, viral infection, cancer, sunstroke fever, abdominal colic, diarrhea, hemorrhage, anthrax, and hepatitis. The objective of this study was to identify the compounds and to evaluate the antimicrobial and antioxidant activity of the extracts and isolated compounds from <i>V. sinaiticum</i>. The <sup>1</sup>H-NMR, <sup>13</sup>C-NMR, and DEPT-135 were used to elucidate the structures of isolated compounds. Essential oils were extracted by hydrodistillation method and their chemical analyses were performed by GC-MS. The broth microdilution method was used to evaluate the antimicrobial activity. The radical scavenging activity of the extracts and isolated compounds were evaluated using DPPH method. Silica gel column chromatographic separation of root extracts afforded seven known compounds: 3'-(4''-methoxy phenyl)-3'-oxo-propionyl hexadecanoate (<b>1</b>), harpagoside (<b>2</b>), pulverulentoside I (<b>3</b>), scrophuloside B4 (<b>4</b>), scropolioside A (<b>5</b>), scropolioside-D2 (<b>6</b>), and harpagide 6-<i>O</i>-β-glucoside (<b>7</b>), which are all reported from this species for the first time. The EO extracts from leaves and roots were the most susceptible to <i>Streptococcus agalactiae</i>, with a 2 mg/mL MIC. The EO from roots was effective against <i>Candida albicans</i> and <i>Trichophyton mentagrophytes</i>, with a MIC of 8 mg/mL. The MeOH and CH<sub>2</sub>Cl<sub>2</sub>/CH<sub>3</sub>OH (1:1) root extracts showed the maximum activity against <i>S. epidermidis</i> with MIC values of 0.25 mg/mL. The strongest antibacterial effects were demonstrated against <i>Staphylococcus epidermidis</i>, which exhibited a 0.0625 mg/mL MIC for compound <b>1</b>. The strongest radical scavenging activity was exhibited by the methanol extract (IC<sub>50</sub> = 3.4 μg/mL), and compounds <b>4</b>, <b>6</b>, <b>5</b>, <b>3</b>, <b>7</b>, and <b>2</b> with IC<sub>50</sub> values of 3.2, 3.38, 3.6, 3.8, 4.2, and 4.7 μg/mL, respectively, in comparison with ascorbic acid (IC<sub>50</sub> = 1.3 μg/mL). The results of the molecular docking analysis of compounds revealed minimal binding energies range from -38.5 to -43.1 kJ/mol, -33.1 to -42.7 kJ/mol, -34.7 to -39.3.7 kJ/mol, -25.5 to -37.6 kJ/mol against human myeloperoxidase (PDB ID: 1DNU), murA enzyme (PDB ID: 1UAE), human topoisomerase II<i>β</i> (PDB ID: 4fm9), <i>S. epidermidis</i> FtsZ (PDB number: 4M8I) proteins, respectively. The docking results and the <i>in vitro</i> antibacterial activity are in good agreement. These findings show that the isolated compounds <b>2</b>-<b>7</b> can act as potential antioxidants and strong antibacterials against <i>Staphylococcus aureus</i> and <i>S. epidermidis</i>. As a result, <i>V. sinaiticum</i> root extracts have the potential to be effective in treating diseases caused by bacteria and free radicals, as long as further investigation has been suggested for the ultimate decision of this plan","PeriodicalId":49344,"journal":{"name":"Zeitschrift Fur Naturforschung Section C-A Journal of Biosciences","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139984306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-29Print Date: 2024-01-29DOI: 10.1515/znc-2023-0119
Mustafa M El-Abadelah, Ahmad H Abdullah, Jalal A Zahra, Salim S Sabri, Sanaa K Bardaweel, Mutasem O Taha
A set of cyclopenten-[g]annelated isoindigos (5a-g) has been prepared and tested for their in vitro antiproliferative activities against MCF-7 and HL60 cells. Among, the N-1-methyl-5'-nitro derivative (5g) displayed the highest activity against HL60 cells (IC50 = 67 nM) and acted as the most potent Flt3 inhibitor. Compounds 5d-g exhibited moderate activity against MCF-7 (IC50 = 50-80 μM).
{"title":"Synthesis and antitumor activity of model cyclopentene-[<i>g</i>]annelated isoindigos.","authors":"Mustafa M El-Abadelah, Ahmad H Abdullah, Jalal A Zahra, Salim S Sabri, Sanaa K Bardaweel, Mutasem O Taha","doi":"10.1515/znc-2023-0119","DOIUrl":"10.1515/znc-2023-0119","url":null,"abstract":"<p><p>A set of cyclopenten-[<i>g</i>]annelated isoindigos (<b>5a-g</b>) has been prepared and tested for their <i>in vitro</i> antiproliferative activities against MCF-7 and HL60 cells. Among, the <i>N</i>-1-methyl-5'-nitro derivative (<b>5g</b>) displayed the highest activity against HL60 cells (IC<sub>50</sub> = 67 nM) and acted as the most potent Flt3 inhibitor. Compounds <b>5d-g</b> exhibited moderate activity against MCF-7 (IC<sub>50</sub> = 50-80 μM).</p>","PeriodicalId":49344,"journal":{"name":"Zeitschrift Fur Naturforschung Section C-A Journal of Biosciences","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139984307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-24Print Date: 2024-01-29DOI: 10.1515/znc-2023-0132
Dina N Abd-Elshafy, Rola Nadeem, Mohamed H Nasraa, Mahmoud M Bahgat
SARS-CoV-2 nsp12, the RNA-dependent RNA-polymerase plays a crucial role in virus replication. Monitoring the effect of its emerging mutants on viral replication and response to antiviral drugs is important. Nsp12 of two Egyptian isolates circulating in 2020 and 2021 were sequenced. Both isolates included P323L, one included the A529V. Tracking A529V mutant frequency, it relates to the transience peaked C.36.3 variant and its parent C.36, both peaked worldwide on February-August 2021, enlisted as high transmissible variants under investigation (VUI) on May 2021. Both Mutants were reported to originate from Egypt and showed an abrupt low frequency upon screening, we analyzed all 1104 nsp12 Egyptian sequences. A529V mutation was in 36 records with an abrupt low frequency on June 2021. As its possible reappearance might obligate actions for a candidate VUI, we analyzed the predicted co-effect of P323L and A529V mutations on protein stability and dynamics through protein structure simulations. Three available structures for drug-nsp12 interaction were used representing remdesivir, suramin and favipiravir drugs. Remdesivir and suramin showed an increase in structure stability and considerable change in flexibility while favipiravir showed an extreme interaction. Results predict a favored efficiency of the drugs except for favipiravir in case of the reported mutations.
{"title":"Analysis of the SARS-CoV-2 nsp12 P323L/A529V mutations: coeffect in the transiently peaking lineage C.36.3 on protein structure and response to treatment in Egyptian records.","authors":"Dina N Abd-Elshafy, Rola Nadeem, Mohamed H Nasraa, Mahmoud M Bahgat","doi":"10.1515/znc-2023-0132","DOIUrl":"10.1515/znc-2023-0132","url":null,"abstract":"<p><p>SARS-CoV-2 nsp12, the RNA-dependent RNA-polymerase plays a crucial role in virus replication. Monitoring the effect of its emerging mutants on viral replication and response to antiviral drugs is important. Nsp12 of two Egyptian isolates circulating in 2020 and 2021 were sequenced. Both isolates included P323L, one included the A529V. Tracking A529V mutant frequency, it relates to the transience peaked C.36.3 variant and its parent C.36, both peaked worldwide on February-August 2021, enlisted as high transmissible variants under investigation (VUI) on May 2021. Both Mutants were reported to originate from Egypt and showed an abrupt low frequency upon screening, we analyzed all 1104 nsp12 Egyptian sequences. A529V mutation was in 36 records with an abrupt low frequency on June 2021. As its possible reappearance might obligate actions for a candidate VUI, we analyzed the predicted co-effect of P323L and A529V mutations on protein stability and dynamics through protein structure simulations. Three available structures for drug-nsp12 interaction were used representing remdesivir, suramin and favipiravir drugs. Remdesivir and suramin showed an increase in structure stability and considerable change in flexibility while favipiravir showed an extreme interaction. Results predict a favored efficiency of the drugs except for favipiravir in case of the reported mutations.</p>","PeriodicalId":49344,"journal":{"name":"Zeitschrift Fur Naturforschung Section C-A Journal of Biosciences","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139542676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Boceprevir drug is a ketoamide serine protease inhibitor with a linear peptidomimetic structure that exhibits inhibition activity against 2019-nCoV main protease. This paper reports electronic properties of boceprevir and its molecular docking as well as molecular dynamics simulation analysis with protein receptor. For this, the equilibrium structure of boceprevir has been obtained by DFT at B3LYP and ωB97XD levels with 6-311+G(d,p) basis set in gas and water mediums. HOMO-LUMO and absorption spectrum analysis have been used to evaluate the boceprevir's toxicity and photosensitivity, respectively. Molecular docking simulation has been performed to test the binding affinity of boceprevir with 2019-nCoV MPRO; which rendered a variety of desirable binding locations between the ligand and target protein's residue positions. The optimum binding location has been considered for molecular dynamics simulation. The findings have been addressed to clarify the boceprevir drug efficacy against the 2019-nCoV MPRO.
{"title":"<i>In silico</i> study of inhibition activity of boceprevir drug against 2019-nCoV main protease.","authors":"Gargi Tiwari, Madan Singh Chauhan, Dipendra Sharma","doi":"10.1515/znc-2023-0117","DOIUrl":"10.1515/znc-2023-0117","url":null,"abstract":"<p><p>Boceprevir drug is a ketoamide serine protease inhibitor with a linear peptidomimetic structure that exhibits inhibition activity against 2019-nCoV main protease. This paper reports electronic properties of boceprevir and its molecular docking as well as molecular dynamics simulation analysis with protein receptor. For this, the equilibrium structure of boceprevir has been obtained by DFT at B3LYP and ωB97XD levels with 6-311+G(d,p) basis set in gas and water mediums. HOMO-LUMO and absorption spectrum analysis have been used to evaluate the boceprevir's toxicity and photosensitivity, respectively. Molecular docking simulation has been performed to test the binding affinity of boceprevir with 2019-nCoV M<sup>PRO</sup>; which rendered a variety of desirable binding locations between the ligand and target protein's residue positions. The optimum binding location has been considered for molecular dynamics simulation. The findings have been addressed to clarify the boceprevir drug efficacy against the 2019-nCoV M<sup>PRO</sup>.</p>","PeriodicalId":49344,"journal":{"name":"Zeitschrift Fur Naturforschung Section C-A Journal of Biosciences","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139058909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-01Print Date: 2023-11-27DOI: 10.1515/znc-2023-0099
Betül Kaya, Leyla Yurttaş, Gülşen Akalın-Çiftçi, Mehmet Onur Aksoy
Abstract A series of new benzoxazole-hydrazone and benzoxazole-1,3,4-oxadiazole derivatives have been designed, synthesized and evaluated as cytotoxic agents toward human A549 lung cancer cells. Compounds 3d, 3e, 5b, 5c, 5d and 5e were the most potent compounds with IC50 values of <3.9, 10.33, 11.6, 5.00, <3.9 and 4.5 μg/mL, respectively, which are higher than reference drug cisplatin (IC50 = 19.00 μg/mL). The flow cytometry-based apoptosis detection assay was performed to determine their effects on apoptosis in A549 cells. All tested compounds induced apoptosis in A549 cell line.
{"title":"Design, synthesis and apoptotic effects of novel benzoxazole compounds.","authors":"Betül Kaya, Leyla Yurttaş, Gülşen Akalın-Çiftçi, Mehmet Onur Aksoy","doi":"10.1515/znc-2023-0099","DOIUrl":"10.1515/znc-2023-0099","url":null,"abstract":"Abstract A series of new benzoxazole-hydrazone and benzoxazole-1,3,4-oxadiazole derivatives have been designed, synthesized and evaluated as cytotoxic agents toward human A549 lung cancer cells. Compounds 3d, 3e, 5b, 5c, 5d and 5e were the most potent compounds with IC50 values of <3.9, 10.33, 11.6, 5.00, <3.9 and 4.5 μg/mL, respectively, which are higher than reference drug cisplatin (IC50 = 19.00 μg/mL). The flow cytometry-based apoptosis detection assay was performed to determine their effects on apoptosis in A549 cells. All tested compounds induced apoptosis in A549 cell line.","PeriodicalId":49344,"journal":{"name":"Zeitschrift Fur Naturforschung Section C-A Journal of Biosciences","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71414978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}