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1.
Future Med Chem ; 16(12): 1185-1203, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38989989

RESUMO

Aim: Synthesis of novel bis-Schiff bases having potent inhibitory activity against phosphodiesterase (PDE-1 and -3) enzymes, potentially offering therapeutic implications for various conditions. Methods: Bis-Schiff bases were synthesized by refluxing 2,4-dihydroxyacetophenone with hydrazine hydrate, followed by treatment of substituted aldehydes with the resulting hydrazone to obtain the product compounds. After structural confirmation, the compounds were screened for their in vitro PDE-1 and -3 inhibitory activities. Results: The prepared compounds exhibited noteworthy inhibitory efficacy against PDE-1 and -3 enzymes by comparing with suramin standard. To clarify the binding interactions between the drugs, PDE-1 and -3 active sites, molecular docking studies were carried out. Conclusion: The potent compounds discovered in this study may be good candidates for drug development.


[Box: see text].


Assuntos
Acetofenonas , Nucleotídeo Cíclico Fosfodiesterase do Tipo 1 , Simulação de Acoplamento Molecular , Inibidores de Fosfodiesterase , Acetofenonas/química , Acetofenonas/farmacologia , Acetofenonas/síntese química , Inibidores de Fosfodiesterase/farmacologia , Inibidores de Fosfodiesterase/síntese química , Inibidores de Fosfodiesterase/química , Humanos , Nucleotídeo Cíclico Fosfodiesterase do Tipo 1/antagonistas & inibidores , Nucleotídeo Cíclico Fosfodiesterase do Tipo 1/metabolismo , Relação Estrutura-Atividade , Estrutura Molecular , Bases de Schiff/química , Bases de Schiff/farmacologia , Bases de Schiff/síntese química , Domínio Catalítico
2.
Bioorg Chem ; 150: 107501, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38865858

RESUMO

In this study, eleven novel acyl hydrazides derivative of polyhydroquinoline were synthesized, characterized and screened for their in vitro anti-diabetic and anti-glycating activities. Seven compounds 2a, 2d, 2i, 2 h, 2j, 2f, and 2 g exhibited notable α-amylase inhibitory activity having IC50 values from 3.51 ± 2.13 to 11.92 ± 2.30 µM. Similarly, six compounds 2d, 2f, 2 h, 2i, 2j, and 2 g displayed potent α-glucosidase inhibitory activity compared to the standard acarbose. Moreover, eight derivatives 2d, 2 g, 2f, 2j, 2a, 2i, 2 g, and 2e showed excellent anti-glycating activity with IC50 values from 6.91 ± 2.66 to 15.80 ± 1.87 µM when compared them with the standard rutin (IC50 = 22.5 ± 0.90 µM). Molecular docking was carried out to predict the binding modes of all the compounds with α-amylase and α-glucosidase. The docking analysis revealed that most of the compounds established strong interactions with α-amylase and α-glucosidase. All compounds fitted well into the binding pockets of α-amylase and α-glucosidase. Among all compounds 2a and 2f were most potent based on docking score -8.2515 and -7.3949 against α-amylase and α-glucosidase respectively. These results hold promise for the development of novel candidates targeted at controlling postprandial glucose levels in individuals with diabetes.


Assuntos
Inibidores de Glicosídeo Hidrolases , Hipoglicemiantes , Simulação de Acoplamento Molecular , alfa-Amilases , alfa-Glucosidases , alfa-Amilases/antagonistas & inibidores , alfa-Amilases/metabolismo , alfa-Glucosidases/metabolismo , Inibidores de Glicosídeo Hidrolases/farmacologia , Inibidores de Glicosídeo Hidrolases/síntese química , Inibidores de Glicosídeo Hidrolases/química , Hipoglicemiantes/farmacologia , Hipoglicemiantes/química , Hipoglicemiantes/síntese química , Relação Estrutura-Atividade , Hidrazinas/química , Hidrazinas/farmacologia , Hidrazinas/síntese química , Estrutura Molecular , Humanos , Relação Dose-Resposta a Droga , Quinolinas/química , Quinolinas/farmacologia , Quinolinas/síntese química , Agentes Antiglicação
3.
J Surg Case Rep ; 2024(6): rjae407, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38859966

RESUMO

Retrocaval ureter is a rare congenital vascular anomaly with an incidence of 0.13%, leading to the passage of the right ureter behind the inferior vena cava and then turning around it to attain its lateral position. The condition is usually associated with obstruction in the right kidney and proximal ureter leading to symptoms like dull aching pain in the flanks, recurrent episodes of urinary tract infections, and recurrent stone formation. The patient presented with recurrent episodes of burning micturition and pain in the right flank for the past 6 months. A contrast-enhanced computed tomography kidney-ureter-bladder was done to diagnose the condition. The patient was managed by open pelviureteric anastomosis lateral to the inferior vena cava, thus eliminating the obstruction on the ureter. The patient has had an uneventful postoperative follow-up. Retrocaval ureter is a rare condition and should be clinically suspected in cases of hydronephrosis where other causes have been ruled out. Different approaches can be used to correct the anomaly. In this case report, an open transperitoneal intraabdominal approach has been used.

4.
Chem Biodivers ; : e202400704, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38781003

RESUMO

Thirteen novel hydrazone-Schiff bases (3-15) of fexofenadine were succesfully synthesized, structurally deduced and finally assessed their capability to inhibit urease enzyme (in vitro). In the series, six compounds 12 (IC50=10.19±0.16 µM), 11 (IC50=15.05±1.11 µM), 10 (IC50=17.01±1.23 µM), 9 (IC50=17.22±0.81 µM), 13 (IC50=19.31±0.18 µM), and 14 (IC50=19.62±0.21 µM) displayed strong inhibitory action better than the standard thiourea (IC50=21.14±0.24 µM), while the remaining compounds displayed significant to less inhibition. LUMO and HOMO showed the transferring of charges from molecules to biological transfer and MEP map showed the chemically reactive zone appropriate for drug action are calculated using DFT. AIM charges, non-bonding orbitals, and ELF are also computed. The urease protein binding analysis benefited from the docking studies.

5.
J Mater Chem B ; 12(24): 5950-5956, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38804847

RESUMO

Therapeutic applications have sparked increased interest in the use of synthetic anion receptors for ion transport across lipid membranes. In this context, the construction of synthetic transmembrane transporters for the physiologically important chloride ion is currently of enormous interest. As a result, considerable effort is being devoted to the design and synthesis of artificial transmembrane chloride ion transporters. However, only inadequate progress has been made in developing macrocyclic chloride ion transporters using the fundamental principles of supramolecular chemistry, and hence this field entails fostering investigations. In this investigation, the synthesis of two new double walled trifluorophenyl/phthalimide extended calix[4]pyrrole (C4P) receptors (3 and 7) has been successfully reported. 1H-NMR titration and HRMS studies confirmed the 1 : 1 binding stoichiometry of the chloride ion with these receptors in the solution phase (only receptor 3b was studied by 1H-NMR). Regarding ion transport of 3b and 7, when studied in the HPTS-based vesicular system, 3b showed better activity with an EC50 value of 0.39 µM. The detailed ion transport studies on 3b have revealed that ion transport occurs through the Cl-/NO3- antiport mode.


Assuntos
Calixarenos , Porfirinas , Membrana Celular/química , Membrana Celular/metabolismo , Modelos Moleculares , Conformação Molecular , Porfirinas/química , Calixarenos/química , Ftalimidas/química , Flúor/química , Cloretos/química , Íons/química
6.
RSC Adv ; 14(16): 10978-10994, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38577436

RESUMO

In recent years, polyhydroquinolines have gained much attention due to their widespread applications in medicine, agriculture, industry, etc. Here, we synthesized a series of novel hydrazone-based polyhydroquinoline derivatives via multi-step reactions. These molecules were characterized by modern spectroscopic techniques (1H-NMR, 13C NMR, and LC-HRMS) and their antibacterial and in vitro α-glucosidase inhibitory activities were assessed. Compound 8 was found to be the most active inhibitor against Listeria monocytogenes NCTC 5348, Bacillus subtilis IM 622, Brevibacillus brevis, and Bacillus subtilis ATCC 6337 with a zone of inhibition of 15.3 ± 0.01, 13.2 ± 0.2, 13.1 ± 0.1, and 12.6 ± 0.3 mm, respectively. Likewise, compound 8 also exhibited the most potent inhibitory potential for α-glucosidase (IC50 = 5.31 ± 0.25 µM) in vitro, followed by compounds 10 (IC50 = 6.70 ± 0.38 µM), and 12 (IC50 = 6.51 ± 0.37 µM). Furthermore, molecular docking and DFT analysis of these compounds showed good agreement with experimental work and the nonlinear optical properties calculated here indicate that these compounds are good candidates for nonlinear optics.

7.
Angew Chem Int Ed Engl ; 63(22): e202403314, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38517056

RESUMO

Artificial ion transport systems have emerged as an important class of compounds that promise applications in chemotherapeutics as anticancer agents or to treat channelopathies. Stimulus-responsive systems that offer spatiotemporally controlled activity for targeted applications remain rare. Here we utilize dynamic hydrogen bonding interactions of a 4,6-dihydroxy-isophthalamide core to generate a modular platform enabling access to stimuli-responsive ion transporters that can be activated in response to a wide variety of external stimuli, including light, redox, and enzymes, with excellent OFF-ON activation profiles. Alkylation of the two free hydroxyl groups with stimulus-responsive moieties locks the amide bonds through intramolecular hydrogen bonding and hence makes them unavailable for anion binding and transport. Triggering using a particular stimulus to cleave both cages reverses the hydrogen bonding arrangement, to generate a highly preorganized anion binding cavity for efficient transmembrane transport. Integration of two cages that are responsive to orthogonal stimuli enables multi-stimuli activation, where both stimuli are required to trigger transport in an AND logic process. Importantly, the strategy provides a facile method to post-functionalize the highly active transporter core with a variety of stimulus-responsive moieties for targeted activation with multiple triggers.


Assuntos
Ligação de Hidrogênio , Ânions/química , Ionóforos/química , Oxirredução , Estrutura Molecular , Transporte de Íons
8.
J Biomol Struct Dyn ; : 1-15, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38385366

RESUMO

This research work reports the synthesis of new derivatives of the hydrazone Schiff bases (1-17) based on polyhydroquinoline nucleus through multistep reactions. HR-ESIMS,1H- and 13C-NMR spectroscopy were used to structurally infer all of the synthesized compounds and lastly evaluated for prolyl oligopeptidase inhibitory activity. All the prepared products displayed good to excellent inhibitory activity when compared with standard z-prolyl-prolinal. Three derivatives 3, 15 and 14 showed excellent inhibition with IC50 values 3.21 ± 0.15 to 5.67 ± 0.18 µM, while the remaining 12 compounds showed significant activity. Docking studies indicated a good correlation with the biochemical potency of compounds estimated in the in-vitro test and showed the potency of compounds 3, 15 and 14. The MD simulation results confirmed the stability of the most potent inhibitors 3, 15 and 14 at 250 ns using the parameters RMSD, RMSF, Rg and number of hydrogen bonds. The RMSD values indicate the stability of the protein backbone in complex with the inhibitors over the simulation time. The RMSF values of the binding site residues indicate that the potent inhibitors contributed to stabilizing these regions of the protein, through formed stable interactions with the protein. The Rg. analysis assesses the overall size and compactness of the complexes. The maintenance of stable hydrogen bonds suggests the existence of favorable binding interactions. SASA analysis suggests that they maintained stable conformations without large-scale exposure to the solvent. These results indicate that the ligand-protein interactions are stable and could be exploited to design new drugs for disease treatment.Communicated by Ramaswamy H. Sarma.

9.
ACS Infect Dis ; 10(2): 371-376, 2024 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-38262044

RESUMO

The development of potent antibacterial agents has become increasingly difficult as bacteria continue to evolve and develop resistance to antibiotics. It is therefore imperative to find effective antimicrobial agents that can address the evolving challenges posed by infectious diseases and antimicrobial resistance. Using artificial transmembrane ion transporters is an emerging and promising avenue to address this issue. We report pyridyl-linked hetero hydrazones as highly efficient transmembrane HCl symporters. These compounds offer an appropriate HCl binding site through cooperative protonation, followed by recognition of chloride ions. HCl transport by these compounds inhibits the growth of different Gram-negative bacterial strains with high efficacy by affecting the cell envelope homeostasis. This specific class of compounds holds substantial promise in the ongoing pursuit of developing highly efficient antibacterial agents.


Assuntos
Anti-Infecciosos , Simportadores , Hidrazonas/farmacologia , Cloretos , Antibacterianos/farmacologia , Antibacterianos/química , Anti-Infecciosos/farmacologia
10.
Bioorg Chem ; 144: 107144, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38281382

RESUMO

A series of twenty-seven bis(acylhydrazones) were successfully synthesized with high yields through a multistep process, which entailed the esterification of hydroxyl groups, hydrazination with an excess of hydrazine hydrate, and subsequent reactions with various carbonyl moieties (aldehydes). In the final stage of synthesis, different chemical species including aromatic, heterocyclic, and aliphatic compounds were integrated into the framework. The resulting compounds were characterized using several spectroscopic techniques (1H NMR, 13C NMR, and mass spectrometry). Their anticholinesterase activities were assessed in vitro by examining their interactions with two cholinesterase enzymes: acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Among the synthesized hits, compounds 3, 5, 6, 9-12, and 14 exhibited good to moderate inhibition of AChE. Specifically, 10 (IC50 = 26.3 ± 0.4 µM) and 11 (IC50 = 28.4 ± 0.5 µM) showed good inhibitory activity against AChE, while 9, 12, 3, and 6 exhibited significant inhibition potential against AChE with IC50 values ranging from 35.2 ± 1.1 µM to 64.4 ± 0.3 µM. On the other hand, 5 (IC50 = 22.0 ± 1.1 µM) and 27 (IC50 = 31.3 ± 1.3 µM) displayed significant, and 19 (IC50 = 92.6 ± 0.4 µM) showed moderate inhibitory potential for BChE. Notably, 5 and 27 exhibited dual inhibition of AChE and BChE, with greater potency than the standard drug galantamine. The binding patterns of these molecules within the binding cavities of AChE and BChE were anticipated by molecular docking which showed good correlation with our in vitro findings. Further structural optimization of these molecules may yield more potent AChE and BChE inhibitors.


Assuntos
Compostos de Bifenilo , Butirilcolinesterase , Inibidores da Colinesterase , Hidrazinas , Inibidores da Colinesterase/química , Butirilcolinesterase/metabolismo , Acetilcolinesterase/metabolismo , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade
11.
J Family Med Prim Care ; 12(10): 2385-2391, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38074239

RESUMO

Background: SARS-CoV-causing COVID-19 resulted in mortality, and the clinic-epidemiological profile at the time of admission of patients who died later could provide an insight into pathophysiological consequences due to infection. Method: Retrospective observational study of 64 RTPCR-confirmed COVID-19 non-survivors was conducted from April - June 2021 and January February 2022. Data were analyzed, and a P value<0.05 was taken as significant. Results: 60.94% and 39.06 % were males and females, and 26.57% & 73.43 % of patients had moderate and severe disease, respectively. Fever, cough, and dyspnea were the most common presenting symptoms. 78.12% and 21.88% had pre-existing (diabetes and hypertension were most common) and no co-morbidities, respectively. 65.62 & 17.19 % of patients had bilateral and unilateral ground glass opacities, respectively. Thrombocytopenia, lymphopenia, neutrophilia, elevated monocytes, and neutrophil-lymphocyte ratio (NLR) of 7.52 were hematological findings. D dimer was elevated. ABG showed low PaO2 and SPO2 %. ALT and AST were elevated. Tachycardia was also present. Compared to the first wave, no significant association of gender with severity was found. However, the percentage of male patients was higher. The association of the duration of stay and co-morbidity with disease severity was significant in both the first and subsequent waves of COVID-19. Conclusion: Co-morbidity, disease severity, and radiological lung opacities play a role in the outcome of COVID-19. The associated findings are hematological, renal, liver, cardiovascular, and arterial blood gas derangements.

12.
Future Med Chem ; 15(23): 2195-2208, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38085012

RESUMO

Background: Medication used to treat Type 2 diabetes by decreasing the absorption of carbohydrates in the intestine consists of α-glucosidase inhibitors. Polyhydroquinoline derivatives have attracted interest as excellent antidiabetic agents. Methods: Polyhydroquinoline derivatives (1-17) were synthesized and tested for in vitro α-glucosidase inhibitory activity. Results: All the synthesized compounds exhibited excellent to good inhibitory activity, having IC50 values from 1.23 ± 0.03 to 73.85 ± 0.61 µM, compared with the standard drug, acarbose. The binding mechanism of these derivatives with α-glucosidase was deduced by docking studies and indicated that a slight variation in the orientation of compounds, affects their binding capability. Conclusion: In order to find new antidiabetic drugs, this study has discovered prospective lead candidates.


Assuntos
Diabetes Mellitus Tipo 2 , alfa-Glucosidases , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , alfa-Glucosidases/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Estudos Prospectivos , Simulação de Acoplamento Molecular , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/química
13.
Bioorg Chem ; 141: 106847, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37722268

RESUMO

The anti-inflammatory and analgesic drugs currently used are associated with several adverse effects and found to be highly unsafe for long-term use. Currently, nineteen novel bis-Schiff base derivatives (1-19) of flurbiprofen have been designed, prepared and assessed for in-vivo analgesic, anti-inflammatory and in vivo acute toxicity evaluation. The structures of the acquired compounds were deduced through modern spectroscopic techniques including HR-ESI-MS, 13C-, and 1H NMR. Amongst the series, compounds 7, 9, and 10 attributed potent activities with 93.89, 92.50, and 90.47% decreased edema, respectively compared to flurbiprofen (90.01%), however, compounds 11 and 15 exhibited significant activity of 90.00% decrease. Out of them, fourteen compounds (1-6, 8, 12-14, and 16-19) displayed good activity in the range of 68.96-86.95%. In case of an analgesic study, all the derivatives significantly (p 0.001) increased the pain threshold time particularly compound 7 had the best analgesic effect (24 ± 2.08 s) in comparison with flurbiprofen (21.66 ± 2.02 s) using hot plate test. Similarly, in the acetic acid-induced writhing test, compound 7 determined a potent inhibitory effect (60.47 %) close to flurbiprofen (59.28%). All the synthesized derivatives were found safe up to the dose of 30 mg/kg, in acute toxicity study. On a molecular scale, the synthesized compounds were modeled through a ligand-based pharmacophore study and molecular docking to have insight into the different possible interactions leading to high inhibition levels against the COX-2 enzyme.


Assuntos
Flurbiprofeno , Humanos , Flurbiprofeno/farmacologia , Flurbiprofeno/química , Inibidores de Ciclo-Oxigenase/farmacologia , Simulação de Acoplamento Molecular , Ciclo-Oxigenase 2 , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Analgésicos/química , Anti-Inflamatórios/química , Edema/induzido quimicamente , Edema/tratamento farmacológico , Anti-Inflamatórios não Esteroides/química , Carragenina
14.
RSC Adv ; 13(36): 25379-25390, 2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37636505

RESUMO

In current research, two functional components, i.e., hydrazone and bisphenol sulfide were combined to get useful supramolecules in medicinal chemistry. Herein 25 new 4,4'-thiodiphenol bis-acylhydrazones were synthesized in good to excellent yields. Initially ethyl-2-chloroacetate was reacted with 4,4'-thiodiphenol, which was further reacted with excess hydrazine hydrate to produce 2,2'-((thiobis(4,1-phenylene))bis(oxy))di(acetohydrazide), which was then combined with various aromatic and aliphatic aldehydes to get the desired products (hydrazones, 4a-4y). The synthesized supramolecules were characterized by contemporary spectroscopic techniques such as 1H NMR, 13C NMR, and mass spectroscopy. The synthetic compound's cholinesterase blocking activity was tested against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes where compounds 4n, and 4h showed excellent inhibitory potential for AChE, while 4b, and 4h, demonstrated most potent inhibition of BChE. The starting compound (SM3) and compounds 4h and SM3 depicted excellent dual inhibitory capabilities for both enzymes. The chemical basis of anticholinesterase activity was investigated using a structure-based molecular docking approach. The biological significance and the ease of synthesis of this class of compounds should be considered in therapeutic development for Alzheimer's disease treatments.

15.
Chem Sci ; 14(33): 8897-8904, 2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37621434

RESUMO

Artificial biomimetic chloride anionophores have shown promising applications as anticancer scaffolds. Importantly, stimuli-responsive chloride transporters that can be selectively activated inside the cancer cells to avoid undesired toxicity to normal, healthy cells are very rare. Particularly, light-responsive systems promise better applicability for photodynamic therapy because of their spatiotemporal controllability, low toxicity, and high tunability. Here, in this work, we report o-nitrobenzyl-linked, benzimidazole-based singly and doubly protected photocaged protransporters 2a, 2b, 3a, and 3b, respectively, and benzimidazole-2-amine-based active transporters 1a-1d. Among the active compounds, trifluoromethyl-based anionophore 1a showed efficient ion transport activity (EC50 = 1.2 ± 0.2 µM). Detailed mechanistic studies revealed Cl-/NO3- antiport as the main ion transport process. Interestingly, double protection with photocages was found to be necessary to achieve the complete "OFF-state" that could be activated by external light. The procarriers were eventually activated inside the MCF-7 cancer cells to induce phototoxic cell death.

16.
Angew Chem Int Ed Engl ; 62(44): e202308842, 2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37478126

RESUMO

Synthetic supramolecular ion transporters find applications as potential therapeutics and as tools for engineering functional membranes. Stimuli-responsive systems enable external control over transport, which is necessary for targeted activation. The Minireview provides an overview of current approaches to developing stimuli-responsive ion transport systems, including channels and mobile carriers, that can be controlled using photo or redox inputs.

17.
Saudi Pharm J ; 31(8): 101688, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37457366

RESUMO

Background: Urease belongs to the family of amid hydrolases with two nickel atoms in their core structure. On the basis of literature survey, this research work is mainly focused on the study of bis-Schiff base derivatives of benzyl phenyl ketone nucleus. Objective: Synthesis of benzyl phenyl ketone based bis-Schiff bases in search of potent urease inhibitors. Method: In the current work, bis-Schiff bases were synthesized through two steps reaction by reacting benzyl phenyl ketone with excess of hydrazine hydrate in ethanol solvent in the first step to get the desired hydrazone. In last, different substituted aromatic aldehydes were refluxed in catalytic amount of acetic acid with the desired hydrazone to obtain bis-Schiff base derivatives in tremendous yields. Using various spectroscopic techniques including FTIR, HR-ESI-MS, and 1H NMR spectroscopy were used to clarify the structures of the created bis-Schiff base derivatives. Results: The prepared compounds were finally screened for their in-vitro urease inhibition activity. All the synthesized derivatives (3-9) showed excellent to less inhibitory activity when compared with standard thiourea (IC50 = 21.15 ± 0.32 µM). Compounds 3 (IC50 = 22.21 ± 0.42 µM), 4 (IC50 = 26.11 ± 0.22 µM) and 6 (IC50 = 28.11 ± 0.22 µM) were found the most active urease inhibitors near to standard thiourea among the synthesized series. Similarly, compound 5 having IC50 value of 34.32 ± 0.65 µM showed significant inhibitory activity against urease enzyme. Furthermore, three compounds 7, 8, and 9 exhibited less activity with IC50 values of 45.91 ± 0.14, 47.91 ± 0.14, and 48.33 ± 0.72 µM respectively. DFT used to calculate frontier molecular orbitals including; HOMO and LUMO to indicate the charge transfer from molecule to biological transfer, and MEP map to indicate the chemically reactive zone suitable for drug action. The electron localization function (ELF), non-bonding orbitals, AIM charges are also calculated. The docking study contributed to the analysis of urease protein binding.

18.
Cureus ; 15(6): e40860, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37489184

RESUMO

Introduction Understanding the dynamics of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) spike antibody titers after natural infection is important for understanding immunological memory. This longitudinal study was conducted to assess the trend in serum SARS-CoV-2 IgG spike antibody titers in a cohort of recovered cases up to nine months after SARS infection. Materials and methods We examined the neutralizing antibody response (IgG spike) in serum samples from a cohort of 86 SARS-CoV-2 quantitative polymerase chain reaction (qPCR)-confirmed infection, comprising cases having minor COVID-19 pneumonia and severity, which was determined by CT severity scores. Patients were enrolled in August/September 2020 and serum samples have been processed at one, three, six, and nine months. CT severity scores were rated between 1-25 and antibody titers≥ 1.4 were considered positive. Results The mean anti-SARS-CoV-2-specific IgG antibody titers at one month, three months, six months, and nine months were 22.02 ± 18.36, 14.62 ± 12.61, 8.93 ± 8.10, and 3.86 ± 5.70, respectively. The difference was statistically significant. The seropositivity rates (titer ≥1.4 IU) were 93.02%, 82.56%, 76.74%, and 58.14% at one, three, six, and nine months after infection, respectively. Cases with severe CT severity scores showed significantly higher mean antibody levels at all follow-up visits.

19.
Environ Sci Pollut Res Int ; 30(30): 75863-75878, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37227635

RESUMO

This study aims to explore the influence of renewable energy consumption (REC), global collaboration in environmental technology development (GCETD), gross domestic product per capita (GDPPC), marine energy generation technologies (MGT), trade openness (TDOT), natural resources (NRs), and carbon dioxide emissions (CO2e) in 34 selected knowledge-based economies from 1990 to 2020. The results show that MGT and REC, an environmentally friendly source of energy, are positively connected with zero carbon emissions, reflecting the ability to serve as an alternative energy option for a sustainable environment. In addition, the study reveals that NRS, such as the accessibility of hydrocarbon resources, can have a positive effect on CO2e, implying that the unsustainable use of NRs may lead to the expansion of CO2e. Additionally, the study pinpoints that GDPPC and TDOT, as a gauge of economic expansion, play an essential part in a carbon-neutral future, suggesting that greater amounts of commercial success could result in greater ecological sustainability. The results also show that GCETD is linked to lower CO2e. This means that working together on an international level helps to improve environmental technologies and slow down the effects of global warming. It is suggested that governments should focus on and encourages GCETD, the use of REC, and TDOT to speed up the path toward zero emissions. Also, decision-makers should think about backing research and development investments in MGT as a potential way to reach zero CO2e in a knowledge-based economies.


Assuntos
Desenvolvimento Econômico , Desenvolvimento Industrial , Energia Renovável , Aquecimento Global , Recursos Naturais , Dióxido de Carbono
20.
Int J Mol Sci ; 24(9)2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37175988

RESUMO

Mangrove ecosystems play curial roles in providing many ecological services and alleviating global climate change. However, they are in decline globally, mainly threatened by human activities and global warming, and organic pollutants, especially PAHs, are among the crucial reasons. Microbial remediation is a cost-effective and environmentally friendly way of alleviating PAH contamination. Therefore, understanding the effects of environmental and nutritional parameters on the biodegradation of polycyclic aromatic hydrocarbons (PAHs) is significant for the bioremediation of PAH contamination. In the present study, five bacterial strains, designated as Bp1 (Genus Rhodococcus), Sp8 (Genus Nitratireductor), Sp13 (Genus Marinobacter), Sp23 (Genus Pseudonocardia), and Sp24 (Genus Mycolicibacterium), have been isolated from mangrove sediment and their ring hydroxylating dioxygenase (RHD) genes have been successfully amplified. Afterward, their degradation abilities were comprehensively evaluated under normal cultural (monoculture and co-culture) and different nutritional (tryptone, yeast extract, peptone, glucose, sucrose, and NPK fertilizer) and environmental (cetyl trimethyl ammonium bromide (CTAB), sodium dodecyl sulfate (SDS)) parameters, as well with different co-contaminants (phenanthrene and naphthalene) and heavy metals (Cd2+, Cu2+, Fe3+, Ni2+, Mg2+, Mn2+, and Co2+). The results showed that strain Sp24 had the highest pyrene degradation rate (85%) in the monoculture experiment after being cultured for 15 days. Adding nitrogen- and carbon-rich sources, including tryptone, peptone, and yeast extract, generally endorsed pyrene degradation. In contrast, the effects of carbon sources (glucose and sucrose) on pyrene degradation were distinct for different bacterial strains. Furthermore, the addition of NPK fertilizer, SDS, Tween-80, phenanthrene, and naphthalene enhanced the bacterial abilities of pyrene removal significantly (p < 0.05). Heavy metals significantly reduced all bacterial isolates' degradation potentials (p < 0.05). The bacterial consortia containing high bio-surfactant-producing strains showed substantially higher pyrene degradation. Moreover, the consortia of three and five bacterial strains showed more degradation efficiency than those of two bacterial strains. These results provide helpful microbial resources for mangrove ecological remediation and insight into optimized culture strategies for the microbial degradation of PAHs.


Assuntos
Metais Pesados , Fenantrenos , Hidrocarbonetos Policíclicos Aromáticos , Humanos , Ecossistema , Fertilizantes , Peptonas/metabolismo , Pirenos/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Fenantrenos/metabolismo , Bactérias , Biodegradação Ambiental , Naftalenos/metabolismo , Metais Pesados/metabolismo
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