Pub Date : 2017-01-30DOI: 10.3390/molecules22020213
Li Pan, Nan Hang, Chao Zhang, Yu Chen, Shuchun Li, Yang Sun, Zhong-Jun Li, Xiangbao Meng
A series of benzo[d]imidazole analogues of thiabenzole were synthesized and their anti-inflammatory activities toward NLRP3 (nucleotide-binding domain leucine-rich repeat containing protein family, pyrin domain-containing 3, also known as cryopyrin or NALP3) inflammasome were evaluated in vitro. Two lead compounds, TBZ-09 and TBZ-21, were identified by anti-production of IL-1β. In the second round of biological evaluation, based on the lead, 34 more compounds were synthesized and their in vitro anti-inflammatory activities were investigated. Several compounds were identified as anti-inflammatory agents that can reduce IL-1β expression in a dose-dependent manner. A preliminary structure–activity relationship is also summarized here.
{"title":"Synthesis and Biological Evaluation of Novel Benzimidazole Derivatives and Analogs Targeting the NLRP3 Inflammasome","authors":"Li Pan, Nan Hang, Chao Zhang, Yu Chen, Shuchun Li, Yang Sun, Zhong-Jun Li, Xiangbao Meng","doi":"10.3390/molecules22020213","DOIUrl":"https://doi.org/10.3390/molecules22020213","url":null,"abstract":"A series of benzo[d]imidazole analogues of thiabenzole were synthesized and their anti-inflammatory activities toward NLRP3 (nucleotide-binding domain leucine-rich repeat containing protein family, pyrin domain-containing 3, also known as cryopyrin or NALP3) inflammasome were evaluated in vitro. Two lead compounds, TBZ-09 and TBZ-21, were identified by anti-production of IL-1β. In the second round of biological evaluation, based on the lead, 34 more compounds were synthesized and their in vitro anti-inflammatory activities were investigated. Several compounds were identified as anti-inflammatory agents that can reduce IL-1β expression in a dose-dependent manner. A preliminary structure–activity relationship is also summarized here.","PeriodicalId":19033,"journal":{"name":"Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86170350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-29DOI: 10.3390/molecules22020209
Y. Marunaka, Rie Marunaka, Hongxin Sun, Toshiro Yamamoto, N. Kanamura, Toshio Inui, Akiyuki Taruno
Disorder of blood pressure control causes serious diseases in the cardiovascular system. This review focuses on the anti-hypertensive action of quercetin, a flavonoid, which is one of the polyphenols characterized as the compounds containing large multiples of phenol structural units, by varying the values of various blood pressure regulatory factors, such as vascular compliance, peripheral vascular resistance, and total blood volume via anti-inflammatory and anti-oxidant actions. In addition to the anti-inflammatory and anti-oxidant actions of quercetin, we especially describe a novel mechanism of quercetin’s action on the cytosolic Cl− concentration ([Cl−]c) and novel roles of the cytosolic Cl− i.e., (1) quercetin elevates [Cl−]c by activating Na+-K+-2Cl− cotransporter 1 (NKCC1) in renal epithelial cells contributing to Na+ reabsorption via the epithelial Na+ channel (ENaC); (2) the quercetin-induced elevation of [Cl−]c in renal epithelial cells diminishes expression of ENaC leading to a decrease in renal Na+ reabsorption; and (3) this reduction of ENaC-mediated Na+ reabsorption in renal epithelial cells drops volume-dependent elevated blood pressure. In this review, we introduce novel, unique mechanisms of quercetin’s anti-hypertensive action via activation of NKCC1 in detail.
{"title":"Actions of Quercetin, a Polyphenol, on Blood Pressure","authors":"Y. Marunaka, Rie Marunaka, Hongxin Sun, Toshiro Yamamoto, N. Kanamura, Toshio Inui, Akiyuki Taruno","doi":"10.3390/molecules22020209","DOIUrl":"https://doi.org/10.3390/molecules22020209","url":null,"abstract":"Disorder of blood pressure control causes serious diseases in the cardiovascular system. This review focuses on the anti-hypertensive action of quercetin, a flavonoid, which is one of the polyphenols characterized as the compounds containing large multiples of phenol structural units, by varying the values of various blood pressure regulatory factors, such as vascular compliance, peripheral vascular resistance, and total blood volume via anti-inflammatory and anti-oxidant actions. In addition to the anti-inflammatory and anti-oxidant actions of quercetin, we especially describe a novel mechanism of quercetin’s action on the cytosolic Cl− concentration ([Cl−]c) and novel roles of the cytosolic Cl− i.e., (1) quercetin elevates [Cl−]c by activating Na+-K+-2Cl− cotransporter 1 (NKCC1) in renal epithelial cells contributing to Na+ reabsorption via the epithelial Na+ channel (ENaC); (2) the quercetin-induced elevation of [Cl−]c in renal epithelial cells diminishes expression of ENaC leading to a decrease in renal Na+ reabsorption; and (3) this reduction of ENaC-mediated Na+ reabsorption in renal epithelial cells drops volume-dependent elevated blood pressure. In this review, we introduce novel, unique mechanisms of quercetin’s anti-hypertensive action via activation of NKCC1 in detail.","PeriodicalId":19033,"journal":{"name":"Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89630656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-28DOI: 10.3390/molecules22020201
D. Lennon, J. M. Winfield
Aspects of the chemistry of selected metal fluorides, which are pertinent to their real or potential use as Lewis acidic, heterogeneous catalysts, are reviewed. Particular attention is paid to β-aluminum trifluoride, aluminum chlorofluoride and aluminas γ and η, whose surfaces become partially fluorinated or chlorinated, through pre-treatment with halogenating reagents or during a catalytic reaction. In these cases, direct comparisons with nanostructured metal fluorides are possible. In the second part of the review, attention is directed to iron(III) and copper(II) metal chlorides, whose Lewis acidity and potential redox function have had important catalytic implications in large-scale chlorohydrocarbons chemistry. Recent work, which highlights the complexity of reactions that can occur in the presence of supported copper(II) chloride as an oxychlorination catalyst, is featured. Although direct comparisons with nanostructured fluorides are not currently possible, the work could be relevant to possible future catalytic developments in nanostructured materials.
{"title":"Metal Fluorides, Metal Chlorides and Halogenated Metal Oxides as Lewis Acidic Heterogeneous Catalysts. Providing Some Context for Nanostructured Metal Fluorides","authors":"D. Lennon, J. M. Winfield","doi":"10.3390/molecules22020201","DOIUrl":"https://doi.org/10.3390/molecules22020201","url":null,"abstract":"Aspects of the chemistry of selected metal fluorides, which are pertinent to their real or potential use as Lewis acidic, heterogeneous catalysts, are reviewed. Particular attention is paid to β-aluminum trifluoride, aluminum chlorofluoride and aluminas γ and η, whose surfaces become partially fluorinated or chlorinated, through pre-treatment with halogenating reagents or during a catalytic reaction. In these cases, direct comparisons with nanostructured metal fluorides are possible. In the second part of the review, attention is directed to iron(III) and copper(II) metal chlorides, whose Lewis acidity and potential redox function have had important catalytic implications in large-scale chlorohydrocarbons chemistry. Recent work, which highlights the complexity of reactions that can occur in the presence of supported copper(II) chloride as an oxychlorination catalyst, is featured. Although direct comparisons with nanostructured fluorides are not currently possible, the work could be relevant to possible future catalytic developments in nanostructured materials.","PeriodicalId":19033,"journal":{"name":"Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry","volume":"223 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79981934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-27DOI: 10.3390/molecules22020205
M. Zhao, Q. Liu, Qiyong Liu, Z. Liu
The screening of Chinese medicinal herbs for insecticidal principles showed that the essential oil of Echinops grijsii Hance roots possessed significant larvicidal activity against mosquitoes. The essential oil was extracted via hydrodistillation and its constituents were determined by gas chromatography-mass spectrometry (GC-MS) analysis. GC-MS analyses revealed the presence of 31 components, with 5-(3-buten-1-yn-1-yl)-2,2′-bithiophene (5-BBT, 27.63%), α-terthienyl (α-T, 14.95%), 1,8-cineole (5.56%) and cis-β-ocimene (5.01%) being the four major constituents. Based bioactivity-directed chromatographic separation of the essential oil led to the isolation of 5-BBT, 5-(4-isovaleroyloxybut-1-ynyl)-2,2′-bithiophene (5-IBT) and α-T as active compounds. The essential oil of E. grijsii exhibited larvicidal activity against the fourth instar larvae of Aedes albopictus, Anopheles sinensis and Culex pipiens pallens with LC50 values of 2.65 μg/mL, 3.43 μg/mL and 1.47 μg/mL, respectively. The isolated thiophenes, 5-BBT and 5-IBT, possessed strong larvicidal activity against the fourth instar larvae of Ae. albopictus (LC50 = 0.34 μg/mL and 0.45 μg/mL, respectively) and An. sinensis (LC50 = 1.36 μg/mL and 5.36 μg/mL, respectively). The two isolated thiophenes also had LC50 values against the fourth instar larvae of C. pipiens pallens of 0.12 μg/mL and 0.33 μg/mL, respectively. The findings indicated that the essential oil of E. grijsii roots and the isolated thiophenes have an excellent potential for use in the control of Ae. albopictus, An. sinensis and C. pipiens pallens larvae and could be used in the search for new, safer and more effective natural compounds as larvicides.
{"title":"Identification of Larvicidal Constituents of the Essential Oil of Echinops grijsii Roots against the Three Species of Mosquitoes","authors":"M. Zhao, Q. Liu, Qiyong Liu, Z. Liu","doi":"10.3390/molecules22020205","DOIUrl":"https://doi.org/10.3390/molecules22020205","url":null,"abstract":"The screening of Chinese medicinal herbs for insecticidal principles showed that the essential oil of Echinops grijsii Hance roots possessed significant larvicidal activity against mosquitoes. The essential oil was extracted via hydrodistillation and its constituents were determined by gas chromatography-mass spectrometry (GC-MS) analysis. GC-MS analyses revealed the presence of 31 components, with 5-(3-buten-1-yn-1-yl)-2,2′-bithiophene (5-BBT, 27.63%), α-terthienyl (α-T, 14.95%), 1,8-cineole (5.56%) and cis-β-ocimene (5.01%) being the four major constituents. Based bioactivity-directed chromatographic separation of the essential oil led to the isolation of 5-BBT, 5-(4-isovaleroyloxybut-1-ynyl)-2,2′-bithiophene (5-IBT) and α-T as active compounds. The essential oil of E. grijsii exhibited larvicidal activity against the fourth instar larvae of Aedes albopictus, Anopheles sinensis and Culex pipiens pallens with LC50 values of 2.65 μg/mL, 3.43 μg/mL and 1.47 μg/mL, respectively. The isolated thiophenes, 5-BBT and 5-IBT, possessed strong larvicidal activity against the fourth instar larvae of Ae. albopictus (LC50 = 0.34 μg/mL and 0.45 μg/mL, respectively) and An. sinensis (LC50 = 1.36 μg/mL and 5.36 μg/mL, respectively). The two isolated thiophenes also had LC50 values against the fourth instar larvae of C. pipiens pallens of 0.12 μg/mL and 0.33 μg/mL, respectively. The findings indicated that the essential oil of E. grijsii roots and the isolated thiophenes have an excellent potential for use in the control of Ae. albopictus, An. sinensis and C. pipiens pallens larvae and could be used in the search for new, safer and more effective natural compounds as larvicides.","PeriodicalId":19033,"journal":{"name":"Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry","volume":"165 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77933321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-27DOI: 10.3390/molecules22020206
A. Bolognesi, M. Bortolotti, M. Battelli, L. Polito
The enzymes called ribosome-inactivating proteins (RIPs) that are able to depurinate nucleic acids and arrest vital cellular functions, including protein synthesis, are still a frontline research field, mostly because of their promising medical applications. The contributions of Stirpe to the development of these studies has been one of the most relevant. After a short biographical introduction, an overview is offered of the main results obtained by his investigations during last 55 years on his main research lines: hyperuricaemia, xanthine oxidoreductase and RIPs.
{"title":"Hyperuricaemia, Xanthine Oxidoreductase and Ribosome-Inactivating Proteins from Plants: The Contributions of Fiorenzo Stirpe to Frontline Research","authors":"A. Bolognesi, M. Bortolotti, M. Battelli, L. Polito","doi":"10.3390/molecules22020206","DOIUrl":"https://doi.org/10.3390/molecules22020206","url":null,"abstract":"The enzymes called ribosome-inactivating proteins (RIPs) that are able to depurinate nucleic acids and arrest vital cellular functions, including protein synthesis, are still a frontline research field, mostly because of their promising medical applications. The contributions of Stirpe to the development of these studies has been one of the most relevant. After a short biographical introduction, an overview is offered of the main results obtained by his investigations during last 55 years on his main research lines: hyperuricaemia, xanthine oxidoreductase and RIPs.","PeriodicalId":19033,"journal":{"name":"Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry","volume":"63 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90353070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-27DOI: 10.3390/molecules22020190
Gulraiz Ahmad, N. Rasool, H. Ikram, Samreen Gul Khan, T. Mahmood, K. Ayub, M. Zubair, Eman J. Al-Zahrani, Usman Ali Rana, M. Akhtar, N. Alitheen
The present study describes palladium-catalyzed one pot Suzuki cross-coupling reaction to synthesize a series of novel pyridine derivatives 2a–2i, 4a–4i. In brief, Suzuki cross-coupling reaction of 5-bromo-2-methylpyridin-3-amine (1) directly or via N-[5-bromo-2-methylpyridine-3-yl]acetamide (3) with several arylboronic acids produced these novel pyridine derivatives in moderate to good yield. Density functional theory (DFT) studies were carried out for the pyridine derivatives 2a–2i and 4a–4i by using B3LYP/6-31G(d,p) basis with the help of GAUSSIAN 09 suite programme. The frontier molecular orbitals analysis, reactivity indices, molecular electrostatic potential and dipole measurements with the help of DFT methods, described the possible reaction pathways and potential candidates as chiral dopants for liquid crystals. The anti-thrombolytic, biofilm inhibition and haemolytic activities of pyridine derivatives were also investigated. In particular, the compound 4b exhibited the highest percentage lysis value (41.32%) against clot formation in human blood among all newly synthesized compounds. In addition, the compound 4f was found to be the most potent against Escherichia coli with an inhibition value of 91.95%. The rest of the pyridine derivatives displayed moderate biological activities.
{"title":"Efficient Synthesis of Novel Pyridine-Based Derivatives via Suzuki Cross-Coupling Reaction of Commercially Available 5-Bromo-2-methylpyridin-3-amine: Quantum Mechanical Investigations and Biological Activities","authors":"Gulraiz Ahmad, N. Rasool, H. Ikram, Samreen Gul Khan, T. Mahmood, K. Ayub, M. Zubair, Eman J. Al-Zahrani, Usman Ali Rana, M. Akhtar, N. Alitheen","doi":"10.3390/molecules22020190","DOIUrl":"https://doi.org/10.3390/molecules22020190","url":null,"abstract":"The present study describes palladium-catalyzed one pot Suzuki cross-coupling reaction to synthesize a series of novel pyridine derivatives 2a–2i, 4a–4i. In brief, Suzuki cross-coupling reaction of 5-bromo-2-methylpyridin-3-amine (1) directly or via N-[5-bromo-2-methylpyridine-3-yl]acetamide (3) with several arylboronic acids produced these novel pyridine derivatives in moderate to good yield. Density functional theory (DFT) studies were carried out for the pyridine derivatives 2a–2i and 4a–4i by using B3LYP/6-31G(d,p) basis with the help of GAUSSIAN 09 suite programme. The frontier molecular orbitals analysis, reactivity indices, molecular electrostatic potential and dipole measurements with the help of DFT methods, described the possible reaction pathways and potential candidates as chiral dopants for liquid crystals. The anti-thrombolytic, biofilm inhibition and haemolytic activities of pyridine derivatives were also investigated. In particular, the compound 4b exhibited the highest percentage lysis value (41.32%) against clot formation in human blood among all newly synthesized compounds. In addition, the compound 4f was found to be the most potent against Escherichia coli with an inhibition value of 91.95%. The rest of the pyridine derivatives displayed moderate biological activities.","PeriodicalId":19033,"journal":{"name":"Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83873910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-26DOI: 10.3390/molecules22020203
Mijat Božović, S. Garzoli, M. Sabatino, F. Pepi, A. Baldisserotto, E. Andreotti, C. Romagnoli, A. Mai, S. Manfredini, R. Ragno
A comprehensive study on essential oils extracted from different Calamintha nepeta (L.) Savi subsp. glandulosa (Req.) Ball samples from Tarquinia (Italy) is reported. In this study, the 24-h steam distillation procedure for essential oil preparation, in terms of different harvesting and extraction times, was applied. The Gas chromatography–mass spectrometry (GC/MS) analysis showed that C. nepeta (L.) Savi subsp. glandulosa (Req.) Ball essential oils from Tarquinia belong to the pulegone-rich chemotype. The analysis of 44 samples revealed that along with pulegone, some other chemicals may participate in exerting the related antifungal activity. The results indicated that for higher activity, the essential oils should be produced with at least a 6-h steam distillation process. Even though it is not so dependent on the period of harvesting, it could be recommended not to harvest the plant in the fruiting stage, since no significant antifungal effect was shown. The maximum essential oil yield was obtained in August, with the highest pulegone percentage. To obtain the oil with a higher content of menthone, September and October should be considered as the optimal periods. Regarding the extraction duration, vegetative stage material gives the oil in the first 3 h, while material from the reproductive phase should be extracted at least at 6 or even 12 h.
{"title":"Essential Oil Extraction, Chemical Analysis and Anti-Candida Activity of Calamintha nepeta (L.) Savi subsp. glandulosa (Req.) Ball—New Approaches","authors":"Mijat Božović, S. Garzoli, M. Sabatino, F. Pepi, A. Baldisserotto, E. Andreotti, C. Romagnoli, A. Mai, S. Manfredini, R. Ragno","doi":"10.3390/molecules22020203","DOIUrl":"https://doi.org/10.3390/molecules22020203","url":null,"abstract":"A comprehensive study on essential oils extracted from different Calamintha nepeta (L.) Savi subsp. glandulosa (Req.) Ball samples from Tarquinia (Italy) is reported. In this study, the 24-h steam distillation procedure for essential oil preparation, in terms of different harvesting and extraction times, was applied. The Gas chromatography–mass spectrometry (GC/MS) analysis showed that C. nepeta (L.) Savi subsp. glandulosa (Req.) Ball essential oils from Tarquinia belong to the pulegone-rich chemotype. The analysis of 44 samples revealed that along with pulegone, some other chemicals may participate in exerting the related antifungal activity. The results indicated that for higher activity, the essential oils should be produced with at least a 6-h steam distillation process. Even though it is not so dependent on the period of harvesting, it could be recommended not to harvest the plant in the fruiting stage, since no significant antifungal effect was shown. The maximum essential oil yield was obtained in August, with the highest pulegone percentage. To obtain the oil with a higher content of menthone, September and October should be considered as the optimal periods. Regarding the extraction duration, vegetative stage material gives the oil in the first 3 h, while material from the reproductive phase should be extracted at least at 6 or even 12 h.","PeriodicalId":19033,"journal":{"name":"Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84586679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-26DOI: 10.3390/molecules22020202
G. Molteni, A. Ponti
Conventional frontier molecular orbital theory is not able to satisfactorily explain the regioselectivity outcome of the nitrilimine–alkene cycloaddition. We considered that conceptual density functional theory (DFT) could be an effective theoretical framework to rationalize the regioselectivity of the title reaction. Several nitrilimine–alkene cycloadditions were analyzed, for which we could find regioselectivity data in the literature. We computed DFT reactivity indices at the B3LYP/6-311G(2d,p)//B3LYP/6-31G(d,p) and employed the grand potential stabilization criterion to calculate the preferred regioisomer. Experimental and calculated regioselectivity agree in the vast majority of cases. It was concluded that predominance of a single regioisomer can be obtained by maximizing (i) the chemical potential difference between nitrilimine and alkene and (ii) the local softness difference between the reactive atomic sites within each reactant. Such maximization can be achieved by carefully selecting the substituents on both reactants.
{"title":"The Nitrilimine–Alkene Cycloaddition Regioselectivity Rationalized by Density Functional Theory Reactivity Indices","authors":"G. Molteni, A. Ponti","doi":"10.3390/molecules22020202","DOIUrl":"https://doi.org/10.3390/molecules22020202","url":null,"abstract":"Conventional frontier molecular orbital theory is not able to satisfactorily explain the regioselectivity outcome of the nitrilimine–alkene cycloaddition. We considered that conceptual density functional theory (DFT) could be an effective theoretical framework to rationalize the regioselectivity of the title reaction. Several nitrilimine–alkene cycloadditions were analyzed, for which we could find regioselectivity data in the literature. We computed DFT reactivity indices at the B3LYP/6-311G(2d,p)//B3LYP/6-31G(d,p) and employed the grand potential stabilization criterion to calculate the preferred regioisomer. Experimental and calculated regioselectivity agree in the vast majority of cases. It was concluded that predominance of a single regioisomer can be obtained by maximizing (i) the chemical potential difference between nitrilimine and alkene and (ii) the local softness difference between the reactive atomic sites within each reactant. Such maximization can be achieved by carefully selecting the substituents on both reactants.","PeriodicalId":19033,"journal":{"name":"Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84634060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-25DOI: 10.3390/molecules22020152
Jiachen Ma, Luqing Zhang, B. Geng, U. Azhar, A. Xu, Shuxiang Zhang
In this work, a thermo-responsive and cross-linked fluoropolymer poly(2,2,2-Trifluoroethyl) methacrylate (PTFEMA) was successfully prepared by reversible addition-fragmentation chain transfer (RAFT) mediated aqueous polymerization with a thermo-responsive diblock poly(dimethylacrylamide-b-N-isopropylacrylamide) (PDMA-b-PNIPAM) that performed a dual function as both a nanoreactor and macro-RAFT agent. The cross-linked polymer particles proved to be in a spherical-like structure of about 50 nm in diameter and with a relatively narrow particle size distribution. 1H-NMR and 19F-NMR spectra showed that thermo-responsive diblock P(DMA-b-NIPAM) and cross-linked PTFEMA particles were successfully synthesized. Influence of the amount of ammonium persulfate (APS), the molar ratio of monomers to RAFT agent, influence of the amount of cross-linker on aqueous polymerization and thermo-responsive characterization of the particles are investigated. Monomer conversion increased from 44% to 94% with increasing the molar ratio of APS and P(DMA-b-NIPAM) from 1:9 to1:3. As the reaction proceeded, the particle size increased from 29 to 49 nm due to the consumption of TFEMA monomer. The size of cross-linked nanoparticles sharply decreased from 50.3 to 40.5 nm over the temperature range 14–44 °C, suggesting good temperature sensitivity for these nanoparticles.
{"title":"Preparation of Thermo-Responsive and Cross-Linked Fluorinated Nanoparticles via RAFT-Mediated Aqueous Polymerization in Nanoreactors","authors":"Jiachen Ma, Luqing Zhang, B. Geng, U. Azhar, A. Xu, Shuxiang Zhang","doi":"10.3390/molecules22020152","DOIUrl":"https://doi.org/10.3390/molecules22020152","url":null,"abstract":"In this work, a thermo-responsive and cross-linked fluoropolymer poly(2,2,2-Trifluoroethyl) methacrylate (PTFEMA) was successfully prepared by reversible addition-fragmentation chain transfer (RAFT) mediated aqueous polymerization with a thermo-responsive diblock poly(dimethylacrylamide-b-N-isopropylacrylamide) (PDMA-b-PNIPAM) that performed a dual function as both a nanoreactor and macro-RAFT agent. The cross-linked polymer particles proved to be in a spherical-like structure of about 50 nm in diameter and with a relatively narrow particle size distribution. 1H-NMR and 19F-NMR spectra showed that thermo-responsive diblock P(DMA-b-NIPAM) and cross-linked PTFEMA particles were successfully synthesized. Influence of the amount of ammonium persulfate (APS), the molar ratio of monomers to RAFT agent, influence of the amount of cross-linker on aqueous polymerization and thermo-responsive characterization of the particles are investigated. Monomer conversion increased from 44% to 94% with increasing the molar ratio of APS and P(DMA-b-NIPAM) from 1:9 to1:3. As the reaction proceeded, the particle size increased from 29 to 49 nm due to the consumption of TFEMA monomer. The size of cross-linked nanoparticles sharply decreased from 50.3 to 40.5 nm over the temperature range 14–44 °C, suggesting good temperature sensitivity for these nanoparticles.","PeriodicalId":19033,"journal":{"name":"Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry","volume":"90 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87696504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-25DOI: 10.3390/molecules22020199
A. Hunyadi, J. Csábi, A. Martins, J. Molnár, Attila Balázs, G. Tóth
P-glycoprotein (P-gp, ABCB1) over-expression, causing a multi-drug resistant (MDR) phenotype, is a major problem in cancer chemotherapy that urgently requires novel approaches. Our previous studies showed certain ecdysteroid derivatives as promising chemo-sensitizers against MDR and non-MDR cancer cell lines while also exerting mild to moderate inhibition of P-gp function. Here we report the preparation of a set of substituted 2,3-dioxolane derivatives of poststerone, a known in vivo metabolite of 20-hydroxyecdysone (20E). In contrast with previously studied ecdysteroid dioxolanes, the majority of the new compounds did not inhibit the efflux function of P-gp. Nevertheless, a strong, dose dependent sensitization to doxorubicin was observed on a P-gp transfected cancer cell line and on its susceptible counterpart. We also observed that the MDR cell line was more sensitive to the compounds’ effect than the non-MDR. Our results showed for the first time that the chemo-sensitizing activity of ecdysteroids can be fully independent of functional efflux pump inhibition, and suggest these compounds as favorable leads against MDR cancer.
p -糖蛋白(P-gp, ABCB1)过表达导致多药耐药(MDR)表型是癌症化疗中的一个主要问题，迫切需要新的治疗方法。我们之前的研究表明，某些表皮甾体衍生物作为耐多药和非耐多药癌细胞系的有希望的化学增敏剂，同时也对P-gp功能有轻度至中度的抑制作用。在这里，我们报道了一组取代的2,3-二恶烷后酮衍生物的制备，后酮是一种已知的20-羟基蜕皮酮(20E)的体内代谢物。与先前研究的外甾类二氧唑烷相比，大多数新化合物不抑制P-gp的外排功能。然而，在P-gp转染的癌细胞系及其易感细胞系上观察到对阿霉素的强剂量依赖性敏化。我们还观察到耐多药细胞系对化合物的作用比非耐多药细胞系更敏感。我们的研究结果首次表明，体外类固醇的化学增敏活性可以完全独立于功能性外排泵抑制，并表明这些化合物是抗耐多药癌症的有利先导。
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