RESUMO
OBJECTIVES: This study aimed to localise the eloquent cortex and measure evoked field (EF) parameters using magnetoencephalography in patients with epilepsy and tumours near the eloquent cortex. METHODS: A total of 41 patients (26 with drug-refractory epilepsy and 15 with tumours), with a mean age of 33 years, were recruited. Visual evoked field (VEF), auditory evoked field (AEF), sensory evoked field (SSEF), and motor-evoked field (MEF) latencies, amplitudes, and localisation were compared with those of a control population. Subgroup analyses were performed based on lobar involvement. Evoked Field parameters on the affected side were compared with those on the opposite side. The effect of distance from the lesion on nearby and distant evoked fields was evaluated. RESULTS: AEF and VEF amplitudes and latencies were reduced bilaterally (p < 0.05). Amplitude in the ipsilateral SSEF was reduced by 29.27% and 2.16% in the AEF group compared to the contralateral side (p = 0.02). In patients with temporal lobe lesions, the SSEF amplitude was reduced bilaterally (p < 0.02), and latency was prolonged compared with controls. The MEF amplitude was reduced and latency was prolonged in patients with frontal lobe lesions (p = 0.01). EF displacement was 32%, 57%, 21%, and 16% for AEF, MEF, VEF, and SSEF respectively. Patients in the epilepsy group had distant EF abnormalities. CONCLUSIONS: EF amplitude was reduced and latency was prolonged in the involved hemisphere. Distant EF amplitudes were more affected than latencies in epilepsy. Amplitude and distance from the lesion had negative correlation for all EF. EF changes indicated eloquent cortical displacement which may not be apparent on MRI.
RESUMO
A novel cationic porphyrin-quinoxaline conjugate 8 was prepared in good yield by the coupling of activated quinoxaline carboxylic acid 5 with an appropriate aminoporphyrin. The UV-vis spectra of conjugate 8 with the addition of ctDNA shows substantial hypochromicity (39%) and a red shift (12 nm) in the Soret band indicating intercalation and self stacking along the surface. The binding constant of conjugate 8 with ctDNA was determined to be 1.26×10(6) M(-1). The porphyrin-quinoxaline conjugate 8 displayed enhanced photocytotoxicity (IC50=0.06 µM) when compared to TMPyP against A549 cancer cells.
Assuntos
Antineoplásicos/química , Porfirinas/química , Quinoxalinas/química , Animais , Antineoplásicos/síntese química , Antineoplásicos/toxicidade , Cátions/química , Bovinos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , DNA/química , DNA/metabolismo , Clivagem do DNA/efeitos dos fármacos , Humanos , Porfirinas/síntese química , Porfirinas/toxicidade , Quinoxalinas/síntese química , Quinoxalinas/toxicidade , Espectrometria de Fluorescência , Raios UltravioletaRESUMO
A Cu(i)-catalyzed azide-alkyne cycloaddition reaction (CuAAC) has been utilized to prepare novel triazole-linked cationic porphyrin-psoralen conjugates that exhibited significant photocytotoxicity against A549 cancer cells (IC50 = 84 nM).
Assuntos
DNA/química , Ficusina/síntese química , Porfirinas/síntese química , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Catálise , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cobre/química , Ficusina/química , Ficusina/farmacologia , Fluorescência , Humanos , Concentração Inibidora 50 , Estrutura Molecular , Porfirinas/química , Porfirinas/farmacologiaRESUMO
INTRODUCTION: Obesity adversely affects the outcome in trauma patients. However, the impact of obesity on the severity of traumatic brain injury (TBI) and outcomes is not well known. This study aimed to explore the impact of obesity/body mass index on the severity and outcomes following TBI. METHODS: A systematic review of the literature was conducted using PRISMA guidelines to answer three questions: Q1: Is obesity/increased BMI associated with less risk of head injury? Q2: Whether obesity is associated with less severity of head injury? Q3: What is the impact of obesity/BMI on outcomes following head injury? A comprehensive search using keywords and MeSH terms was conducted in PUBMED, Cochrane database, Google Scholar, SCOPUS, WEB of Science Core Collection, and ScIELO index (Last day of search 06.06.2021). We used the Newcastle-Ottawa assessment scale (NOS) to evaluate the quality of studies and the Cochrane ROBANS tool to evaluate the risk of bias. Data extraction was done using piloted forms, and meta-analysis was done using the Mantel-Haenszel method. RESULTS: A total of 1088 citations were obtained with the search strategy. Eighteen studies matched inclusion and exclusion criteria and were included in the systematic review. The median quality of studies was 7/9 in NOS. There were fewer occurrences of head injury in obese individuals with an odd's ratio of 0.80% and 95% CI (0.69-0.93) with p = 0.004. More patients with BMI ≥ 30 had GCS ≤ 8 than patients with BMI < 30 with OR 1.08 (95%CI: 1.02-1.14). Obese patients had a more severe head injury (as per AIS) (58.9% vs 44.2%) and OR 1.83 (95%CI: 1.72-1.94), I2 = 87% and p < 0.00001. Length of ICU stay was more in obese individuals with a standard mean difference of 0.29 (95% CI: 0.03-0.55), I2 = 87%, p = 0.03. Similarly, obese individuals had a more extended hospital stay. There was no difference in mortality or ventilator days between obese and non-obese TBI patients. CONCLUSIONS: Obesity was associated with lower incidence and higher severity of head injury. However, there was no conclusive evidence that obesity confers protection from sustaining a head injury. Though the length of hospital and ICU stay were longer in obese individuals, the impact of obesity on mortality was not significant. There was no conclusive evidence for association of obesity with long term functional outcome or mortality following TBI.
Assuntos
Lesões Encefálicas Traumáticas , Obesidade , Índice de Massa Corporal , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/epidemiologia , Humanos , Tempo de Internação , Obesidade/complicações , Obesidade/epidemiologiaRESUMO
A few thienyl substituted pyrazole derivatives were synthesized to aid in the characterization of the cannabinoid receptor antagonist and also to serve as potentially useful antiobesity agent. Structural requirements for selective CB1 receptor antagonistic activity of 5-thienyl pyrazole derivatives included the structural similarity with potent, specific antagonist rimonabant 1. Compound 3 has been identified as a hair growth stimulator and an antiobesity agent in animal models.
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Química Farmacêutica/métodos , Cabelo/efeitos dos fármacos , Obesidade/tratamento farmacológico , Piperidinas/síntese química , Pirazóis/síntese química , Receptor CB1 de Canabinoide/antagonistas & inibidores , Animais , Benzoxazinas/farmacologia , Células CHO , Cricetinae , Cricetulus , AMP Cíclico/metabolismo , Desenho de Fármacos , Concentração Inibidora 50 , Modelos Químicos , Morfolinas/farmacologia , Naftalenos/farmacologia , Piperidinas/farmacologia , Pirazóis/farmacologia , RimonabantoRESUMO
Design, synthesis and conformational analysis of few imidazole and oxazole as bioisosters of 4S-(-)-3-(4-chlorophenyl)-N-methyl-N'-[(4-chlorophenyl)-sulfonyl]-4-phenyl-4,5-dihydro-1H-pyrazole-1-caboxamidine (SLV-319) 2 is reported. Computer assisted conformational analysis gave a direct clue for the loss of CB1 antagonistic activity of the ligands without a fine docking simulation for the homology model.
Assuntos
Imidazóis/química , Imidazóis/farmacologia , Modelos Moleculares , Oxazóis/química , Oxazóis/farmacologia , Pirazóis/química , Pirazóis/farmacologia , Receptor CB1 de Canabinoide/antagonistas & inibidores , Sulfonamidas/química , Sulfonamidas/farmacologia , Animais , Técnicas de Química Combinatória , Cricetinae , Cricetulus , Desenho de Fármacos , Humanos , Imidazóis/síntese química , Estrutura Molecular , Oxazóis/síntese química , Pirazóis/síntese química , Relação Estrutura-Atividade , Sulfonamidas/síntese químicaRESUMO
Design and synthesis of novel piperazinylaryloxazolidinones possessing heteroaryl groups are described and their in vitro antibacterial activities have been evaluated by MIC assay. Compounds (S)-N-[3-{3-fluoro-4-[4-[3-(5-nitrofuran-2-yl)-acryloyl]-piperazin-1-yl]-phenyl}-2-oxo-oxazolidin-5-yl-methyl] acetamide (6o), (S)-N-[3-{3-fluoro-4-[4-[3-(5-nitrothien-2-yl)-acryloyl]-piperazin-1-yl]-phenyl}-2-oxo-oxazolidin-5-yl-methyl] acetamide (6p) and N-oxide of (S)-N-[3-{3-fluoro-4-[4-[3-(5-nitrofuran-2-yl)-acryloyl]-piperazin-1-yl]-phenyl}-2-oxo-oxazolidin-5-yl-methyl] acetamide (9) showed superior antibacterial activities than linezolid and also active against the linezolid resistant Staphylococcus aureus strains.
Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Oxazolidinonas/síntese química , Oxazolidinonas/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Acetamidas/farmacologia , Antibacterianos/química , Desenho de Fármacos , Linezolida , Testes de Sensibilidade Microbiana , Estrutura Molecular , Oxazolidinonas/química , Relação Estrutura-AtividadeRESUMO
α-Aminomethyl tetrazoles, recently made accessible by an Ugi multicomponent reaction (MCR), were shown to be excellent starting materials for a further Ugi MCR, yielding substituted N-methyl-2-(((1-methyl-1H-tetrazol-5-yl)methyl)amino)acetamides having four points of diversity in a library-to-library approach. The scope and limitations of the two-step sequence was explored by conducting more than 50 reactions. Irrespective of electron-rich and electron-deficient oxo-components and the nature of the isocyanide component, the reactions give excellent yields. Sterically less hindered α-aminomethyl tetrazoles give better yields of in further Ugi MCR. The target scaffold has four points of diversity and is finding applications to fill screening decks for high-throughput screening (HTS) in the European Lead Factory and in structure-based drug design.
Assuntos
Acetamidas/síntese química , Técnicas de Química Combinatória/métodos , Bibliotecas de Moléculas Pequenas/síntese química , Tetrazóis/síntese química , Cianetos/química , Ensaios de Triagem em Larga Escala/métodos , Modelos Moleculares , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
A number of analogues of diaryl dihydropyrazole-3-carboxamides have been synthesized. Their activities were evaluated for appetite suppression and body weight reduction in animal models. Depending on the chemical modification of the selected dihydropyrazole scaffold, the lead compounds--the bisulfate salt of (+/-)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid morpholin-4-ylamide 26 and the bisulfate salt of (-)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid morpholin-4-ylamide 30--showed significant body weight reduction in vivo, which is attributed to their CB1 antagonistic activity and exhibited a favorable pharmacokinetic profile. The molecular modeling studies also showed interactions of two isomers of (+/-)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid morpholin-4-ylamide 9 with CB1 receptor in the homology model similar to those of N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole-carboxamide (rimonabant) 1 and 4S-(-)-3-(4-chlorophenyl)-N-methyl-N'-[(4-chlorophenyl)-sulfonyl]-4-phenyl-4,5-dihydro-1H-pyrazole-1-carboxamidine (SLV-319) 2.
Assuntos
Amidas/síntese química , Fármacos Antiobesidade/síntese química , Pirazóis/síntese química , Amidas/farmacocinética , Amidas/farmacologia , Animais , Fármacos Antiobesidade/farmacocinética , Fármacos Antiobesidade/farmacologia , Depressores do Apetite/síntese química , Depressores do Apetite/farmacocinética , Depressores do Apetite/farmacologia , Peso Corporal/efeitos dos fármacos , Feminino , Modelos Moleculares , Morfolinas/síntese química , Morfolinas/farmacocinética , Morfolinas/farmacologia , Piperidinas/química , Pirazóis/química , Pirazóis/farmacocinética , Pirazóis/farmacologia , Ratos , Ratos Zucker , Receptor CB1 de Canabinoide/antagonistas & inibidores , Rimonabanto , Estereoisomerismo , Relação Estrutura-Atividade , Sulfonamidas/químicaRESUMO
Isocyanides are the "Jekyll and Hyde" of organic chemistry allowing for extremely interesting transformations that are not only extremely odorous but also noxious. Therefore, an isocyanide-less isocyanide-based multicomponent reaction (IMCR) has been developed, and this protocol is expected to replace many of the old procedures in the future not only in IMCR but in other areas of organic chemistry as well.
Assuntos
Cianetos/química , Estrutura MolecularRESUMO
Employing a click chemistry approach we have synthesized a novel triazole-linked cationic porphyrin-ß-carboline conjugate which exhibited remarkable photocytotoxicity against the A549 cancer cell line (IC(50) = 60 nM).
Assuntos
Antineoplásicos/farmacologia , Carbolinas/farmacologia , Metaloporfirinas/farmacologia , Porfirinas/farmacologia , Zinco/química , Linhagem Celular Tumoral , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Metaloporfirinas/síntese química , Fotoquimioterapia , Triazóis/farmacologiaRESUMO
Synthesis and antibacterial activity of a number of substituted 4,5,6,7-tetrahydro-thieno[3,2-c]pyridine quinolones is reported. The antibacterial activities were evaluated in standard in vitro MIC assay method. Some of the compounds showed in vitro (MIC) antibacterial activity comparable to those of Gatifloxacin, Ciprofloxacin, and Sparfloxacin.
Assuntos
Antibacterianos/síntese química , Química Farmacêutica/métodos , Piridinas/química , Quinolonas/química , Quinolonas/síntese química , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Ciprofloxacina/farmacologia , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos , Resistência Microbiana a Medicamentos , Fluoroquinolonas/farmacologia , Gatifloxacina , Testes de Sensibilidade Microbiana , Modelos Químicos , Conformação MolecularRESUMO
Design and synthesis of a few novel methylamino piperidinyl substituted oxazolidinones are reported. Their antibacterial activities have been evaluated in a MIC assay against broader panel of both susceptible and resistant Gram-positive strains. (S)-N-{3-[3-Fluoro-4-(methyl-{1-[3-(5-nitrofuran-2-yl)-acryloyl]-piperidin-4-yl}-amino)-phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide 4i has shown comparable antibacterial activity to linezolid and eperezolid in the MIC assay, additionally compound 4i showed good antibacterial activity with an in vitro MIC value of 2-4 microg/mL against linezolid resistant Staphylococcus aureus (linezolid 16 microg/mL).