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991.
992.
Oksana V. Salomatina Nadezhda S. Dyrkheeva Irina I. Popadyuk Alexandra L. Zakharenko Ekaterina S. Ilina Nina I. Komarova Jhannes Reynisson Nariman F. Salakhutdinov Olga I. Lavrik Konstantin P. Volcho 《Molecules (Basel, Switzerland)》2022,27(1)
A series of deoxycholic acid (DCA) amides containing benzyl ether groups on the steroid core were tested against the tyrosyl-DNA phosphodiesterase 1 (TDP1) and 2 (TDP2) enzymes. In addition, 1,2,4- and 1,3,4-oxadiazole derivatives were synthesized to study the linker influence between a para-bromophenyl moiety and the steroid scaffold. The DCA derivatives demonstrated promising inhibitory activity against TDP1 with IC50 in the submicromolar range. Furthermore, the amides and the 1,3,4-oxadiazole derivatives inhibited the TDP2 enzyme but at substantially higher concentration. Tryptamide 5 and para-bromoanilide 8 derivatives containing benzyloxy substituent at the C-3 position and non-substituted hydroxy group at C-12 on the DCA scaffold inhibited both TDP1 and TDP2 as well as enhanced the cytotoxicity of topotecan in non-toxic concentration in vitro. According to molecular modeling, ligand 5 is anchored into the catalytic pocket of TDP1 by one hydrogen bond to the backbone of Gly458 as well as by π–π stacking between the indolyl rings of the ligand and Tyr590, resulting in excellent activity. It can therefore be concluded that these derivatives contribute to the development of specific TDP1 and TDP2 inhibitors for adjuvant therapy against cancer in combination with topoisomerase poisons. 相似文献
993.
Dr. Cecilia Lindgren Dr. Nina Forsgren Norman Hoster Christine Akfur Elisabet Artursson Dr. Lotta Edvinsson Dr. Richard Svensson Dr. Franz Worek Dr. Fredrik Ekström Prof. Anna Linusson 《Chemistry (Weinheim an der Bergstrasse, Germany)》2022,28(40):e202200678
Reactivators are vital for the treatment of organophosphorus nerve agent (OPNA) intoxication but new alternatives are needed due to their limited clinical applicability. The toxicity of OPNAs stems from covalent inhibition of the essential enzyme acetylcholinesterase (AChE), which reactivators relieve via a chemical reaction with the inactivated enzyme. Here, we present new strategies and tools for developing reactivators. We discover suitable inhibitor scaffolds by using an activity-independent competition assay to study non-covalent interactions with OPNA-AChEs and transform these inhibitors into broad-spectrum reactivators. Moreover, we identify determinants of reactivation efficiency by analysing reactivation and pre-reactivation kinetics together with structural data. Our results show that new OPNA reactivators can be discovered rationally by exploiting detailed knowledge of the reactivation mechanism of OPNA-inhibited AChE. 相似文献
994.
Digna Vázquez-García Margarita López-Torres Nina Gómez-Blanco José M. Vila Jesús J. Fernández 《Journal of organometallic chemistry》2011,696(3):764-771
Treatment of the halogen-bridged complexes [Pd{2,5-Me2C6H2C(H)N(2,4,6-Me3C6H2)-C6,N}(μ-X)]2 (1a, X = Cl; 2a, X = Br) with the tertiary diphosphine Ph2PCH2PPh2 (dppm), regardless of the molar ratio used, gave a mixture of two complexes: [Pd{2,5-Me2C6H2C(H)N(2,4,6-Me3C6H2)-C6}(μ-Ph2PCH2PPh2)2(μ-X)]2[PF6] (5a, X = Cl; 6a, X = Br), which presents an A-frame structure, and [Pd{2,5-Me2C6H2C(H)N(2,4,6-Me3C6H2)-C6,N}(Ph2PCH2PPh2-P,P)][PF6], 3a, with the diphosphine as chelating. The mixture could be separated and the corresponding complexes isolated. However, reaction of 1a and 2a with the diphosphine Ph2PC(CH2)PPh2 (vdpp) exclusively gave the mononuclear complex [Pd{2,5-Me2C6H2C(H)N(2,4,6-Me3C6H2)-C6,N}{Ph2PC(CH2)PPh2-P,P}][PF6], 4a, analogous to 3a. Treatment of the halogen-bridged complexes [Pd{1-CH2-2-[HCN(2,4,6-Me3C6H2)]-4-MeC6H3-C,N}(μ-X)]2 (1a′, X = Cl; 2a′, X = Br) with dppm or vdpp in a cyclometallated complex/diphosphine 1:2 M ratio, gave mononuclear complexes with the chelating diphospines [Pd{1-CH2-2-[HCN(2,4,6-Me3C6H2)]-4-MeC6H3-C,N}(Ph2PCH2PPh2-P,P)][PF6], 3a′, and [Pd{1-CH2-2-[HCN(2,4,6-Me3C6H2)]-4-MeC6H3-C,N}{Ph2PC(CH2)PPh2-P,P}][PF6], 4a′. When the reaction was carried out using a cyclometallated complex/diphosphine 1:1 M ratio the dinuclear complexes [{Pd[1-CH2-2-{HCN(2,4,6-Me3C6H2)}-4-MeC6H3-C,N]}2(μ-X)(μ-Ph2PCH2PPh2)][Cl], (5a′, X = Cl; 7a′, X = Br) and [{Pd[1-CH2-2-{HCN(2,4,6-Me3C6H2)}-4-MeC6H3-C,N]}2(μ-Cl){μ-Ph2PC(CH2)PPh2}][Cl], 6a′, were obtained. The molecular structures of complexes 3a, 4a, 5a and 6a′ were determined by X-ray single crystal diffraction. 相似文献
995.
Nina Warner Ilja Gasan Osojnik rnivec Vijay Kumar Rana Menandro Cruz Oren A. Scherman 《Molecules (Basel, Switzerland)》2022,27(7)
The encapsulation of proteins into core-shell structures is a widely utilised strategy for controlling protein stability, delivery and release. Despite the recognised utility of these microstructures, however, core-shell fabrication routes are often too costly or poorly scalable to allow for industrial translation. Furthermore, many scalable routes rely upon emulsion-techniques implicating denaturing or environmentally harmful organic solvents. Herein, we investigate core-shell protein encapsulation through single-feed, aqueous spray drying: a cheap, industrially ubiquitous particle-formation technology in the absence of organic solvents. We show that an excipient’s preference for the surface of the spray dried particle is well-predicted by its hydrodynamic diameter (D) under relevant feed buffer conditions (pH and ionic strength) and that the predictive power of D is improved when measured at the spray dryer outlet temperature compared to room temperature ( = 0.64 vs. 0.59). Lastly, we leverage these findings to propose an adaptable design framework for fabricating core-shell protein encapsulates by single-feed aqueous spray drying. 相似文献
996.
Numerous benzothiazole derivatives are used in organic synthesis, in various industrial and consumer products, and in drugs, with a wide spectrum of biological activity. As the properties of the benzothiazole moiety are strongly affected by the nature and position of substitutions, in this review, covering the literature from 2016, we focus on C-2-substituted benzothiazoles, including the methods of their synthesis, structural modification, reaction mechanisms, and possible pharmacological activity. The synthetic approaches to these heterocycles include both traditional multistep reactions and one-pot atom economy processes using green chemistry principles and easily available reagents. Special attention is paid to the methods of the thiazole ring closure and chemical modification by the introduction of pharmacophore groups. 相似文献
997.
Itumeleng Seotsanyana-Mokhosi Nina Kuznetsova Tebello Nyokong 《Journal of photochemistry and photobiology. A, Chemistry》2001,140(3):215-222
Tetra-2,3-pyridinoporphyrazines and the corresponding water-soluble N,N′,N′′,N′′′-tetramethyl-tetra-2,3-pyridinoporphyrazine complexes, containing central metal atoms; M=Ge, Sn, Si and Zn, were synthesized and their photochemical properties were investigated. The reductive quenching of pyridinoporphyrazines excited states, enhanced relative to phthalocyanines, was considered as the first photochemical step of dyes phototransformation in dimethylformamide (DMF) and dimethylsulfoxide (DMSO) solutions under irradiation with visible light. Efficiency of singlet oxygen photosensitization decreases significantly in the row phthalocyanines, unquaternized, quaternized tetra-2,3-pyridinoporphyrazine metallocomplexes. 相似文献
998.
999.
Maa Kenda Nina Ko
evar Glava
Milan Nagy Marija Sollner Dolenc 《Molecules (Basel, Switzerland)》2021,26(24)
Herbal products are often used as an alternative to pharmacological therapy. Menopausal symptoms and gynecological disorders (such as premenstrual syndrome and dysmenorrhea) are the indications where pharmacological therapy may have serious adverse events, hence many women prefer to use herbal products to help with these symptoms. Here, we reviewed plants and derived products, which are commonly used for the abovementioned indications, focusing on clinical data, safely profile and whether or not their use is justified. We noted that limited data are available on the use of some plants for alleviating the symptoms of menopause and gynecological disorders. While black cohosh (Cimicifuga racemose) and red clover (Trifolium pretense) were consistently shown to help reduce menopausal symptoms in clinical studies, currently available data do not fully support the use of fenugreek (Trigonella foenum-graecum), hops (Humulus lupulus), valerian (Valeriana officinalis), and soybean (Glycine max and Glycine soja) for this indication. For premenstrual syndrome and premenstrual dysphoric disorder, chaste tree (Vitex agnus-castus) shows effectiveness, but more clinical studies are needed to confirm such effect upon the use of evening primrose (Oenothera biennis). 相似文献
1000.
Nina E. Wezynfeld Arkadiusz M. Bonna Dawid Ponka Wojciech Bal Tomasz Frczyk 《Molecules (Basel, Switzerland)》2022,27(17)
Nickel is toxic to humans. Its compounds are carcinogenic. Furthermore, nickel allergy is a severe health problem that affects approximately 10–20% of humans. The mechanism by which these conditions develop remains unclear, but it may involve the cleavage of specific proteins by nickel ions. Ni(II) ions cleave the peptide bond preceding the Ser/Thr-Xaa-His sequence. Such sequences are present in all four enzymes of the melatonin biosynthesis pathway, i.e., tryptophan 5-hydroxylase 1, aromatic-l-amino-acid decarboxylase, serotonin N-acetyltransferase, and acetylserotonin O-methyltransferase. Moreover, fragments prone to Ni(II) are exposed on surfaces of these proteins. Our results indicate that all four studied fragments undergo cleavage within tens of hours at pH 8.2 and 37 °C, corresponding with the conditions in the mitochondrial matrix. Since melatonin, a potent antioxidant and anti-inflammatory agent, is synthesized within the mitochondria of virtually all human cells, depleting its supply may be detrimental, e.g., by raising the oxidative stress level. Intriguingly, Ni(II) ions have been shown to mimic hypoxia through the stabilization of HIF-1α protein, but melatonin prevents the action of HIF-1α. Considering all this, the enzymes of the melatonin biosynthesis pathway seem to be a toxicological target for Ni(II) ions. 相似文献