RESUMO
To explore the reaction universality of bridge nitration, the mononitration of different p-tert-butylcalix[4]arene derivatives was executed with tert-butyl nitrite as a nitration reagent. The effects of calix[4]arene conformations, substituents on the lower rim, and reaction conditions on bridge mononitration are systematically studied. The bridge nitration of p-tert-butylcalix[4]arene derivatives in 1,3-alternate, 1,2-alternate, and partial cone conformations can be smoothly executed while that of p-tert-butylcalix[4]arene derivatives strictly regulated in a cone conformation cannot. The nitration product complexity shows a positive correlation with the bridge-hydrogen types, and the optimal bridge-mononitrated substrate is calix[4]arene with only one bridge-hydrogen type. The electron-withdrawing substituent on the lower rim is apparently beneficial for the bridge mononitration. As a result, a variety of bridging chiral p-tert-butylcalix[4]arenes with a mononitro bridge substituent have been successfully synthesized. The highest bridge-mononitrated yield can reach 27% from 1,3-alternate p-tert-butylcalix[4]arene biscrown-5 under optimal reaction conditions.
RESUMO
BACKGROUND Lacrimal gland pleomorphic adenoma (LGPA) is the most common clinically benign epithelial tumor of the lacrimal gland and is predominantly comprised of epithelial cells and interstitial components. At present, the exact pathogenesis of LGPA remains unclear. Previous research has indicated that the occurrence of LGPA may be related to excessive cell proliferation. MATERIAL AND METHODS This study observed the clinicopathological characteristics of LGPA and investigated the tumorigenesis mechanism of cell over-proliferation caused by the imbalance between apoptosis and proliferation. A total of 27 cases were collected from the Department of Ophthalmology of the Affiliated Hospital of Chengde Medical University and the Third Medical Center of Chinese PLA General Hospital from April 2017 to November 2019. Hematoxylin-eosin (HE) staining and immunohistochemical staining were used to observe the pathological characteristics and analyze the expression of bcl-2 and bax in the lacrimal gland. RESULTS Compared with normal lacrimal gland tissues, LGPA tumor tissues had obvious changes in pathological morphology. The expression of bcl-2 in LGPA lesion tissues was dramatically higher (P<0.001), the expression of bax was not significantly different between groups (P=0.25), but the ratio of bcl-2/bax was significantly higher in tumor tissues (P=0.01). CONCLUSIONS We found that the lacrimal gland tumor tissues had obvious excessive proliferation in pathomorphology, which revealed the necessity of complete surgical removal of the capsule from the perspective of pathological morphology and provided a theoretical basis for the hypothesis that the imbalance between apoptosis and proliferation could lead to cell hyperproliferation.
Assuntos
Adenoma Pleomorfo/metabolismo , Adenoma Pleomorfo/patologia , Aparelho Lacrimal/patologia , Adulto , Apoptose/fisiologia , Carcinogênese/metabolismo , Proliferação de Células/fisiologia , Transformação Celular Neoplásica/patologia , Neoplasias Oculares/patologia , Neoplasias Oculares/cirurgia , Feminino , Humanos , Doenças do Aparelho Lacrimal/patologia , Doenças do Aparelho Lacrimal/cirurgia , Masculino , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/patologia , Proteínas Proto-Oncogênicas c-bcl-2/análise , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Proteína X Associada a bcl-2/análiseRESUMO
In order to prepare bridging chiral p-tert-butylcalix[4]crown-5 with a mononitro bridge substituent in a 1,3-alternate conformation, a mononitration method of calix[4]arene bridging methylene has been first developed with tert-butyl nitrite as a nitration reagent. The effects of solvent, reaction temperature, reaction time, and nitration reagent dosage on bridge mononitration have been deeply explored to obtain an optimal nitration condition. The facile nitration presents a new key for calix[4]arene bridge derivatization. After further modification and diastereoisomeric resolution, a pair of bridging chiral p-tert-butylcalix[4]arenes with a monoamino bridge substituent were produced from the bridge-mono-nitrated calix[4]arene. Their preliminary catalysis results in the Henry reaction show good catalytic activities (up to 95% yield) and still low but obviously enhanced enantioselectivities (up to 22.3% ee from 7a, 6% ee from 1), which confirms that the structural transformation indeed improves asymmetric catalysis performances of bridging chiral calix[4]crown-5 amines in a 1,3-alternate conformation.
RESUMO
AIM: To study the imaging characteristics of lacrimal punctum lesion with optical coherence tomography (OCT), and provide imaging basis for the diagnosis and treatment of lacrimal punctum diseases. METHODS: A total of 25 patients (28 eyes) with epiphora and lacrimal puncta lesions were enrolled. Lacrimal puncta lesions included: punctum membrane obstruction in 7 cases (9 eyes), punctum agenesis in 1 case (1 eye), a mass protruded from the punctum in 1 case (1 eye), slit puncta in 1 case (1 eye), peri-puncta mass in 2 cases (2 eyes), chronic dacryocystitis in 4 cases (4 eyes), and primary puncta stenosis in 9 cases (10 eyes; 3 eyes mild, 4 eyes moderate and 3 eyes severe). All patients were examined by slit lamp microscopy and OCT to observe the morphological characteristics of abnormal punctum. RESULTS: Two types of complete membrane obstruction and incomplete membrane obstruction of puncta were observed in OCT images of 7 patients. No lacrimal punctum and lacrimal canalicular cavity were found in 1 case with punctum agenesis. OCT images showed that a narrow lumen remained in the lacrimal puncta in 1 patient with a mass protruded from the punctum. OCT of punctum in a patient with slit punctum after stent placement showed stent and abnormal lacrimal structure. No abnormal intraluminal structure was found in 2 cases of peri-puncta mass after OCT scan, and the lacunar space was narrower than that of the contralateral eye. OCT of puncta in 4 patients with chronic dacryocystitis showed that pus floated in tear with lump-like medium-low reflex. In 9 patients with primary lacrimal puncta stenosis, OCT image could clearly show the changes of puncta lumen in different degrees and shapes. CONCLUSION: OCT is feasible for the examination of pathological punctum, and can provide imaging basis for the diagnosis and treatment of punctum disease.
RESUMO
Thirty-six novel threoninamide carbamate derivatives were designed and synthesised using active fragment-based pharmacophore model. Antifungal activities of these compounds were tested against Oomycete fungi Phytophthora capsici in vitro and in vivo. Interestingly, compound I-1, I-2, I-3, I-6 and I-7 exhibited moderate control effect (>50%) against Pseudoperonospora cubensis in greenhouse at 6.25 µg/mL, which is better than that of control. Meanwhile most of these compounds exhibited significant inhibitory against P. capsici. The other nine fungi were also tested. More importantly, some compounds exhibited remarkably high activities against Sclerotinia sclerotiorum, P. piricola and R. solan in vitro with EC50 values of 3.74-9.76 µg/mL. It is possible that the model is reliabile and this method can be used to discover lead compounds for the development of fungicides.
Assuntos
Amidas/farmacologia , Antifúngicos/farmacologia , Desenho de Fármacos , Fungos/efeitos dos fármacos , Treonina/farmacologia , Amidas/síntese química , Amidas/química , Antifúngicos/síntese química , Antifúngicos/química , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade , Treonina/síntese química , Treonina/químicaRESUMO
Protein tyrosine phosphatase 1B (PTP1B) is a key negative regulator of insulin signaling pathway, and more and more studies have shown that it is a potential target for the treatment of type 2 diabetes mellitus (T2DM). In this study, 17 new 4-thiazolinone derivatives were designed and synthesized as novel PTP1B inhibitors, and ADMET prediction confirmed that these compounds were to be drug-like. In vitro enzyme activity experiments were performed on these compounds, and it was found that a plurality of compounds had good inhibitory activity and high selectivity against PTP1B protein. Among them, compound 7p exhibited the best inhibitory activity with an IC50 of 0.92 µM. The binding mode of compound 7p and PTP1B protein was explored, revealing the reason for its high efficiency. In addition, molecular dynamics simulations for the PTP1BWT and PTP1Bcomp#7p systems revealed the effects of compound 7p on PTP1B protein at the molecular level. In summary, the study reported for the first time that 4-thiazolinone derivatives as a novel PTP1B inhibitor had good inhibitory activity and selectivity for the treatment of T2DM, providing more options for the development of PTP1B inhibitors. AbbreviationsBBBblood-brain barrierCDC25Bcell division cycle 25 homolog BCYP2D6Cytochrome P450 2D6 bindingDCCMdynamic cross-correlation mapDSDiscovery StudioH bondhydrogen bondHIAhuman intestinal absorptionLARleukocyte antigen-related phosphataseMDmolecular dynamicsMEG-2maternal-effect germ-cell defective 2MM-PBSAmolecular mechanics Poisson Boltzmann surface area)PCAprincipal component analysisPDBProtein Data BankpNPPp-nitrophenyl phosphatePPBplasma protein bindingPTP1Bprotein tyrosine phosphotase 1BRMSDroot mean square deviationRMSFroot mean square fluctuationSHP-1src homologous phosphatase-1SHP-2src homologous phosphatase-2SPCsingle-point chargeTCPTPT cell protein tyrosine phosphataseT2DMType 2 diabetes mellitusVDWvan der WaalsCommunicated by Ramaswamy H. Sarma.
Assuntos
Inibidores Enzimáticos , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Diabetes Mellitus Tipo 2 , Inibidores Enzimáticos/farmacologia , Humanos , Insulina , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Relação Estrutura-AtividadeRESUMO
Cell division cycle 25B is a key cell cycle regulator and widely considered as potent clinical drug target for cancers. This research focused on identifying potential compounds in theory which are able to disrupt transient interactions between CDC25B and its CDK2/Cyclin A substrate.By using the method of ZDOCK and RDOCK, the most optimized 3D structure of CDK2/Cyclin A in complex with CDC25B was constructed and validated using two methods: 1) the superimposition of proteins; 2) analysis of the hydrogen bond distances of Arg 488(N1)-Asp 206(OD1), Arg 492(NE)-Asp 206(OD1), Arg 492(N1)-Asp 206(OD2) and Tyr 497(NE)-Asp 210(OD1). A series of new compounds was gained through searching the fragment database derived from ZINC based on the known inhibitor-compound 7 by the means of "replace fragment" technique. The compounds acquired via meeting the requirements of the absorption, distribution, metabolism, and excretion (ADME) predictions. Finally, 12 compounds with better binding affinity were identified. The comp#1, as a representative, was selected to be synthesized and assayed for their CDC25B inhibitory activities. The comp#1 exhibited mild inhibitory activities against human CDC25B with IC50 values at about 39.02 µM. Molecular Dynamic (MD) simulation revealed that the new inhibitor-comp#1 had favorable conformations for binding to CDC25B and disturbing the interactions between CDC25B and CDK2/Cyclin A.
Assuntos
Antineoplásicos/química , Ciclina A/química , Quinase 2 Dependente de Ciclina/química , Desenho de Fármacos , Inibidores Enzimáticos/química , Modelos Moleculares , Fosfatases cdc25/química , Antineoplásicos/farmacologia , Sítios de Ligação , Ciclina A/metabolismo , Quinase 2 Dependente de Ciclina/metabolismo , Inibidores Enzimáticos/farmacologia , Humanos , Ligação de Hidrogênio , Conformação Molecular , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Complexos Multiproteicos/química , Complexos Multiproteicos/metabolismo , Ligação Proteica/efeitos dos fármacos , Relação Estrutura-Atividade , Fosfatases cdc25/antagonistas & inibidores , Fosfatases cdc25/metabolismoRESUMO
Protein tyrosine phosphatase 1B (PTP1B) plays a vital role in the regulation of insulin sensitivity and dephosphorylation of the insulin receptor, so PTP1B inhibitors may be potential agents to treat type 2 diabetes. In this work, a series of novel imidazolidine-2,4-dione derivatives were designed, synthesized and assayed for their PTP1B inhibitory activities. These compounds exhibited potent activities with IC50 values at 0.57-172 µM. A 3D-QSAR study using CoMFA and CoMSIA techniques was carried out to explore structure activity relationship of these molecules. The CoMSIA model was more predictive with q(2) = 0.777, r(2) = 0.999, SEE = 0.013 and r(2)pred = 0.836, while the CoMFA model gave q(2) = 0.543, r(2) = 0.998, SEE = 0.029 and r(2)pred = 0.754. The contour maps derived from the best CoMFA and CoMSIA models combined with docking analysis provided good insights into the structural features relevant to the bioactivity, and could be used in the molecular design of novel imidazolidine-2,4-dione derivatives.
Assuntos
Inibidores Enzimáticos/farmacologia , Imidazolidinas/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Relação Quantitativa Estrutura-Atividade , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Humanos , Imidazolidinas/síntese química , Imidazolidinas/química , Modelos Moleculares , Estrutura Molecular , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Relação Estrutura-AtividadeRESUMO
The cell division cycle 25 (Cdc25) family of proteins is a group of highly conserved dual specificity phosphatases that regulate cyclin-dependent kinases and represent a group of attractive drug targets for anticancer therapies. To develop novel Cdc25B inhibitors, the ZINC database was screened for finding optimal fragments with de novo design approaches. As a result, top 11 compounds with higher binding affinities in flexible docking were obtained, which were derived from five novel scaffolds (scaffold C) consisting of the linker-part and two isolated scaffolds (scaffold A and B)located in the two binding domains (catalytic pocket and swimming pool), respectively. The subsequent molecular docking and molecular dynamics studies showed that these compounds not only adopt more favorable conformations but also have stronger binding interaction with receptor than the inhibitors identified previously. The additional absorption, distribution, metabolism, excretion and toxicity (ADMET) predictions also indicted that the 11 compounds (especially Comp#1) hold a high potential to be novel lead compounds for anticarcinogen. Consequently, the findings reported here may at least provide a new strategy or useful insights for designing effective Cdc25B inhibitors.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Domínio Catalítico/efeitos dos fármacos , Desenho de Fármacos , Neoplasias/tratamento farmacológico , Fosfatases cdc25/antagonistas & inibidores , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Neoplasias/metabolismo , Fosfatases cdc25/química , Fosfatases cdc25/metabolismoRESUMO
Due to the vital role in many cell regulatory processes, such as cell cycle control, survival and apoptosis, as well as growth and neurotransmitter signaling, Src homology 2 (SH2) domain-containing phosphatase 2(Shp2) has attracted considerable attention for developing drugs to treat cancers. In this study, by means of the powerful "core hopping" technique, a novel class of inhibitors was discovered based on the compound II-B08. It was observed by molecular dynamics simulations that these novel inhibitors not only possessed the same function as II-B08 did in inhibiting Shp2, but also had stronger binding to the receptor. It was further validated by the outcomes of their ADME (absorption, distribution, metabolism, and excretion) predictions that the new inhibitors hold high potential to become promising drug candidates for developing novel and powerful drugs for anticancer. Subsequently, in vitro evaluation of promising hits revealed a novel and selective inhibitor of Shp2.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Desenho de Fármacos , Proteína Tirosina Fosfatase não Receptora Tipo 11/antagonistas & inibidores , Humanos , Simulação de Dinâmica Molecular , Neoplasias/tratamento farmacológico , Proteína Tirosina Fosfatase não Receptora Tipo 11/química , Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismoRESUMO
Owing to its special role as a negative regulator in both insulin and leptin signaling, protein tyrosine phosphatase-1B (PTP1B) has drawn considerable attention as a target for treating type 2 diabetes and obesity. It, however, is a great challenge to discover inhibitors specific to each PTP due to the highly homologous. In this study, a series of compounds were discovered to inhibit PTP1B based on imidazolidine-2,4-dione by means of 'core hopping'. A selective PTP1B inhibitor (comp#h) was identified, and molecular dynamics simulation and binding free energy calculation were carried out to propose the most likely binding mode of comp#h with PTP1B. The findings reported here may provide a new strategy in discovering selective and effective inhibitors for treating diabetes.
Assuntos
Desenho de Fármacos , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Imidazolidinas/química , Imidazolidinas/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Proteína Tirosina Fosfatase não Receptora Tipo 2/antagonistas & inibidores , Sítios de Ligação , Diabetes Mellitus Tipo 2/tratamento farmacológico , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/metabolismo , Inibidores Enzimáticos/uso terapêutico , Humanos , Imidazolidinas/metabolismo , Imidazolidinas/uso terapêutico , Simulação de Acoplamento Molecular , Ligação Proteica , Estrutura Terciária de Proteína , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 2/metabolismo , TermodinâmicaRESUMO
The crystal complex propofol/GLIC (the bacterial homologue from Gloeobacter violaceus) recently determined also showed sensitivity to general anesthetics, belonging to the pLGIC (pentameric ligand-gated ion channels) family as a homopentameric member, which are potentiated and inhibited by general anesthetics and mimic changes elicited by anesthetics in physiologic targets as ion channels, providing the useful information for general anesthetics and allosteric modulators design. Thirteen active compounds selected from the previous data sets are used as reference and seed structures for developing novel general anesthetics via the scoring function of lead optimization using pharmacophoric & shape similarity integrated in Muse™ molecular design workflow. Autodock4.0 is validated its accuracy by two computational procedures and used for docking calculations in this study. Finally, the top ten invented propofol analogs reported here exhibit more favorable binding energies geometric matching than propofol. Especially, the comp#1 fits the binding site well in geometric shape with the lowest binding energy than any other compounds, and makes the hydrophobic interaction with the binding site formed by M4 helixes and lipids of receptor as well. More importantly, the interactions between ligand and lipids caused by general-anesthetic binding would be specially considered in novel general anesthetic design. accordingly, the findings reported here may provide useful insights for discovering more effective general anesthetics.
Assuntos
Anestésicos Gerais/química , Ativação do Canal Iônico , Ligantes , Propofol/química , Sítios de Ligação , Simulação por Computador , Cianobactérias/química , Humanos , Canais Iônicos de Abertura Ativada por Ligante/química , Lipídeos/química , Modelos Moleculares , Propofol/análogos & derivados , Ligação ProteicaRESUMO
In our search for environmentally benign insecticides with high activity, low toxicity and low residue, a novel series of amides containing N- pyridylpyrazole moieties were designed and synthesized. The structures of the title compounds were characterized and confirmed by 1H-NMR and elemental analysis. Furthermore, the structure of compound 7l was determined by single crystal X-ray diffraction. The preliminary bioassay tests showed that some of them exhibited good insecticidal activities against Mythimna separata Walker, Plutella xylostella (Linnaeus, 1758) and Laphygma exigua Hübner.
Assuntos
Amidas/química , Amidas/síntese química , Inseticidas/química , Inseticidas/síntese química , Mariposas , Pirazóis/análise , Animais , Desenho de Fármacos , Estrutura Molecular , Pirazóis/química , Relação Estrutura-AtividadeRESUMO
The title compound, C(19)H(15)ClN(2)O(5)S, contains two mol-ecules (A and B) in the asymmetric unit. In mol-ecule A, the dihedral angles between the thia-zole ring and the pendant chloro-benzene and nitro-benzene rings are 72.14â (15) and 3.03â (15)°, respectively. The corresponding angles for mol-ecule B are 45.56â (16) and 1.51â (14)°, respectively. In the crystal, both mol-ecules form inversion dimers linked by pairs of weak C-Hâ¯O inter-actions.
RESUMO
A series of isosteric analogs of mandipropamid were designed and synthesized via 'click chemistry'. The amide bond of mandipropamid was substituted by a 1,2,3-triazole functional group. The bioassay results have indicated that some of the title compounds exhibited moderate fungicidal activity against Pseudoperonospora cubensis, and the activity has been systematically studied as a function of molecular structure. The low activity of the mandipropamid analog that contains a lipid chain is likely due to the presence of a weak hydrogen bond donor in the 1,2,3-triazole. Furthermore, we have performed the molecular modeling and found that N-methylamide could be more effective than amide as the surrogates to 1,2,3-triazole, which ultimately leads to a longer distance (1.1 Å longer) between the two substitutes in the 1,4-disubstituted 1,2,3-triazole compound.
Assuntos
Amidas/síntese química , Amidas/farmacologia , Antifúngicos/síntese química , Antifúngicos/farmacologia , Ácidos Carboxílicos/síntese química , Ácidos Carboxílicos/farmacologia , Oomicetos/efeitos dos fármacos , Amidas/química , Ácidos Carboxílicos/química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas por Ionização por Electrospray , Relação Estrutura-AtividadeRESUMO
Owing to its unique function in assisting the release of newly formed virus particles from the surface of an infected cell, neuraminidase, an antigenic glycoprotein enzyme, is a main target for drug design against influenza viruses. The group-1 neuraminidase of influenza virus possesses a 150-cavity, which is adjacent to the active pocket, and which renders conformational change from the 'open' form to the 'closed' form when the enzyme is binding with a ligand. Using AutoGrow evolutionary algorithm, one very unique fragment is screened out from the fragment databases by exploiting additional interactions with the 150-cavity. Subsequently, three derivatives were constructed by linking the unique fragment to oseltamivir at its three different sites. The three derivatives thus formed show much stronger inhibition power than oseltamivir, and hence may become excellent candidates for developing new and more powerful drugs for treating influenza. Or at the very least, the findings may stimulate new strategy or provide useful insights for working on the target vitally important to the health of human beings.
Assuntos
Antivirais/farmacologia , Inibidores Enzimáticos/farmacologia , Proteína HN/efeitos dos fármacos , Orthomyxoviridae/enzimologia , Oseltamivir/análogos & derivados , Proteína HN/química , Humanos , Orthomyxoviridae/efeitos dos fármacos , Conformação ProteicaRESUMO
PURPOSE: Human dental plaque is implicated in a number of oral diseases. Collection of its undisturbed intact structure facilitates observing the formation and the effect of treatment. This study established a model in vivo to collect intact natural dental plaque biofilm, and observed the features and evaluated the immediate penetration and bactericidal effect of an essential oil (EO) mouthrinse on it at different periods. METHODS: Three 500 microm wide grooves were cut into hydroxyapatite (HA) discs. The discs were worn by six volunteers for 6, 24 and 48 hours, then broken into halves, one served as control, while the other received a one-minute extra-oral EO mouthrinse treatment. 5, 15 and 30 minutes later, the plaque was visualized with a vitality staining technique to observe the sustained changes of biofilm structure in situ and the effect of EO on intact biofilm. The biofilm thickness and fluorescent density of vital and total bacteria were obtained through diagram analysis, assessing the percentage of thickness and fluorescent density of vital to total bacteria. All data analysis was performed using SPSS 13.0 software package. One-way ANOVA and Student-Neuman-Keuls tests were used. RESULTS: The thickness of 6h, 24h and 48 h biofilm was (11.92 + or - 4.63) microm, (18.63 + or - 4.66)microm, (27.55 + or - 6.35) microm, respectively, which increased significantly within 48 hours (P<0.05), especially those within 6 hours. The percentages of thickness and fluorescent density of vital to total bacteria at different periods showed no significant changes (P>0.05). For 6-hour samples, plaque vitality for thickness and fluorescent density decreased significantly within 5 minutes after exposure to the EO (P<0.05). Meanwhile, for 24, 48-hour samples, plaque vitality decreased significantly within 15 minutes (P<0.05). CONCLUSIONS: This study successfully establishes a model for collecting natural undisturbed plaque biofilm in situ, showing the changes constantly within 48 hours. EO mouthrinse has an immediate penetration and antimicrobial effect on the sustained dental plaque biofilm, especially 15 minutes later.
Assuntos
Biofilmes , Placa Dentária , Análise de Variância , Anti-Infecciosos Locais , Estudos Cross-Over , Humanos , Antissépticos BucaisRESUMO
A series of new acrylamide derivatives containing 1,2,3-thiadiazole were synthesized, characterized, and evaluated for their anti-hepatitis B virus (HBV) activities in vitro. The IC50 of compounds 9b (10.4 microg/mL), 9c (3.59 microg/mL) and 17a (9.00 microg/mL) of the inhibition on the replication of HBV DNA were higher than that of the positive control lamivudine (14.8 microg/mL). Compound 9d exhibited significant activity against secretion of HBeAg (IC50=12.26 microg/mL).
Assuntos
Acrilamida/farmacologia , Antivirais/síntese química , Antivirais/farmacologia , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/fisiologia , Tiadiazóis/química , Replicação Viral/efeitos dos fármacos , Acrilamida/síntese química , Acrilamida/química , Antivirais/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cristalografia por Raios X , Humanos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , EstereoisomerismoRESUMO
Ketol-acid reductoisomerase (KARI; EC 1.1.1.86) catalyzes the second common step in branched-chain amino acid biosynthesis. This enzyme is an important target for drug design. Based on the crystal structure of ketol-acid reductoisomerase/N-hydroxy-N-isopropyloxamate (IpOHA) complex, we have carried out high throughput receptor-based virtual screening of the ZINC/drug like database (2 000 000 compounds) to look for novel inhibitors of KARI for the first time. Some novel compounds were found to inhibit rice KARI in vitro among 15 procured compounds. This method can provide useful information for further design and discovery of KARI inhibitors.
Assuntos
Inibidores Enzimáticos/síntese química , Ensaios de Triagem em Larga Escala , Cetol-Ácido Redutoisomerase/antagonistas & inibidores , Domínio Catalítico , Bases de Dados Factuais , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Cetol-Ácido Redutoisomerase/metabolismo , Ligação ProteicaRESUMO
In the title compound, C(10)H(10)N(2)O(3), the dihedral angle between the benzene and imidazolidine rings is 6.0â (4)°, consistent with an essentially planar mol-ecule. In the crystal, inter-molecular N-Hâ¯O hydrogen bonding between centrosymmetrically related mol-ecules leads to loosely associated dimeric aggregates. These are connected into a three-dimensional network by C-Hâ¯O inter-actions, as well as π-π inter-actions [centroid-centroid distances = 3.705â (3) and 3.622â (3)â Å] between the imidazolidine and benzene rings.