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1.
Mol Biol Rep ; 49(10): 9737-9748, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35441939

RESUMO

Biosynthesis and regulation of nicotinamide adenine dinucleotide (NAD+) has recently gained a lot of attention. A systemic decline in NAD+ across many tissues is associated with all the hallmarks of aging. NAD+ can affect a variety of cellular processes, including metabolic pathways, DNA repair, and immune cell activity, both directly and indirectly. These cellular processes play a vital role in maintaining homeostasis, but as people get older, their tissue and cellular NAD+ levels decrease, and this drop in NAD+ levels has been connected to a number of age-related disorders. By restoring NAD+ levels, several of these age-related disorders can be delayed or even reversed. Some of the new studies conducted in mice and humans have targeted the NAD+ metabolism with NAD+ intermediates. Of these, nicotinamide mononucleotide (NMN) has been shown to offer great therapeutic potential with promising results in age-related chronic conditions such as diabetes, cardiovascular issues, cognitive impairment, and many others. Further, human interventions are required to study the long-term effects of supplementing NMN with varying doses. The paper focuses on reviewing the importance of NAD+ on human aging and survival, biosynthesis of NAD+ from its precursors, key clinical trial findings, and the role of NMN on various health conditions.


Assuntos
NAD , Mononucleotídeo de Nicotinamida , Envelhecimento/metabolismo , Animais , Doença Crônica , Humanos , Longevidade , Camundongos , NAD/metabolismo , Mononucleotídeo de Nicotinamida/metabolismo , Mononucleotídeo de Nicotinamida/farmacologia , Mononucleotídeo de Nicotinamida/uso terapêutico
2.
Int J Mol Sci ; 23(2)2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35054912

RESUMO

At present, the potential role of the AgNPs/endo-fullerene molecule metal nano-composite has been evaluated over the biosystems in-vitro. The intra-atomic configuration of the fullerene molecule (C60) has been studied in-vitro for the anti-proliferative activity of human breast adenocarcinoma (MDA-MB-231) cell lines and antimicrobial activity against a few human pathogens that have been augmented with the pristine surface plasmonic electrons and antibiotic activity of AgNPs. Furthermore, FTIR revealed the basic vibrational signatures at ~3300 cm-1, 1023 cm-1, 1400 cm-1 for O-H, C-O, and C-H groups, respectively, for the carbon and oxygen atoms of the C60 molecule. NMR studies exhibited the different footprints and magnetic moments at ~7.285 ppm, explaining the unique underlying electrochemical attributes of the fullerene molecule. Such unique electronic and physico-chemical properties of the caged carbon structure raise hope for applications into the drug delivery domain. The in-vitro dose-dependent application of C60 elicits a toxic response against both the breast adenocarcinoma cell lines and pathogenic microbes. That enables the use of AgNPs decorated C60 endo fullerene molecules to design an effective anti-cancerous drug delivery and antimicrobial agent in the future, bringing a revolutionary change in the perspective of a treatment regime.


Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Fulerenos/química , Nanopartículas Metálicas/química , Prata/química , Antioxidantes/química , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Nanopartículas Metálicas/ultraestrutura , Nanocompostos/química , Análise Espectral
3.
Beilstein J Org Chem ; 17: 2377-2384, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34621399

RESUMO

Herein, a series of novel 1H-1,2,3-triazole and carboxylate derivatives of metronidazole (5a-i and 7a-e) were synthesized and evaluated for their antimicrobial activity in vitro. All the newly synthesized compounds were characterized by 1H NMR, 13C NMR, HRMS, and 19F NMR (5b, 5c and 5h) spectroscopy wherever applicable. The structures of compounds 3, 5c and 7b were unambiguously confirmed by single crystal X-ray analysis diffraction method. Single crystal X-ray structure analysis supported the formation of the metronidazole derivatives. The antimicrobial (antifungal and antibacterial) activity of the prepared compounds was studied. All compounds (except 2 and 3) showed a potent inhibition rate of fungal growth as compared to control and metronidazole. The synthetic compounds also showed higher bacterial growth inhibiting effects compared to the activity of the parent compound. Amongst the tested compounds 5b, 5c, 5e, 7b and 7e displayed excellent potent antimicrobial activity. The current study has demonstrated the usefulness of the 1H-1,2,3-triazole moiety in the metronidazole skeleton.

4.
Brief Bioinform ; 19(2): 263-276, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-27881431

RESUMO

Drug combinations have been proposed as a promising therapeutic strategy to overcome drug resistance and improve efficacy of monotherapy regimens in cancer. This strategy aims at targeting multiple components of this complex disease. Despite the increasing number of drug combinations in use, many of them were empirically found in the clinic, and the molecular mechanisms underlying these drug combinations are often unclear. These challenges call for rational, systematic approaches for drug combination discovery. Although high-throughput screening of single-agent therapeutics has been successfully implemented, it is not feasible to test all possible drug combinations, even for a reduced subset of anticancer drugs. Hence, in vitro and in vivo screening of a large number of drug combinations are not practical. Therefore, devising computational methods to efficiently explore the space of drug combinations and to discover efficacious combinations has attracted a lot of attention from the scientific community in the past few years. Nevertheless, in the absence of consensus regarding the computational approaches used to predict efficacious drug combinations, a plethora of methods, techniques and hypotheses have been developed to date, while the research field lacks an elaborate categorization of the existing computational methods and the available data sources. In this manuscript, we review and categorize the state-of-the-art computational approaches for drug combination prediction, and elaborate on the limitations of these methods and the existing challenges. We also discuss about the recent pan-cancer drug combination data sets and their importance in revising the available methods or developing more performant approaches.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biologia Computacional/métodos , Descoberta de Drogas , Neoplasias/tratamento farmacológico , Animais , Humanos
5.
Bioinformatics ; 35(22): 4830-4833, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31198954

RESUMO

MOTIVATION: High-throughput molecular profiles of human cells have been used in predictive computational approaches for stratification of healthy and malignant phenotypes and identification of their biological states. In this regard, pathway activities have been used as biological features in unsupervised and supervised learning schemes. RESULTS: We developed SIGN (Similarity Identification in Gene expressioN), a flexible open-source R package facilitating the use of pathway activities and their expression patterns to identify similarities between biological samples. We defined a new measure, the transcriptional similarity coefficient, which captures similarity of gene expression patterns, instead of quantifying overall activity, in biological pathways between the samples. To demonstrate the utility of SIGN in biomedical research, we establish that SIGN discriminates subtypes of breast tumors and patients with good or poor overall survival. SIGN outperforms the best models in DREAM challenge in predicting survival of breast cancer patients using the data from the Molecular Taxonomy of Breast Cancer International Consortium. In summary, SIGN can be used as a new tool for interrogating pathway activity and gene expression patterns in unsupervised and supervised learning schemes to improve prognostic risk estimation for cancer patients by the biomedical research community. AVAILABILITY AND IMPLEMENTATION: An open-source R package is available (https://cran.r-project.org/web/packages/SIGN/).


Assuntos
Expressão Gênica , Software , Neoplasias da Mama , Humanos
6.
Molecules ; 25(8)2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32326105

RESUMO

Pyranone natural products have attracted great attention in recent years from chemists and biologists due to their fascinating stereoisomeric structural features and impressive bioactivities. A large number of stereoselective total syntheses of these compounds have been described in the literature. The natural pyranones with long side chains have recently received significant importance in the synthetic field. In the present article, we aim to review the modern progress of the stereoselective total syntheses of these natural pyranones containing long-chain substituents.


Assuntos
Produtos Biológicos/química , Produtos Biológicos/farmacologia , Estrutura Molecular , Estereoisomerismo , Relação Estrutura-Atividade
7.
Bioorg Chem ; 91: 103182, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31404793

RESUMO

Diabetes is a non-communicable disease, which occurs either due to the lack of insulin or the inability of the human body to recognize it. The recent data indicates an increase in the trend of people diagnosed with Type 2 diabetes mellitus (T2DM). α-Glucosidase inhibitors are known to reduce the impact of carbohydrates on blood glucose level and prevent the digestion of carbohydrates. α-glucosidase inhibitors hold great potential for the treatment of T2DM. In search of better α-glucosidase inhibitors, a series of novel (R)-4-fluorophenyl-1H-1,2,3-triazole derivatives were synthesized (6 and 8a-n) and evaluated for their α-glucosidase inhibitory activity in vitro. All new compounds were characterized by 1H NMR, 13C NMR, 19F NMR, ESI-MS, and where applicable by single crystal X-ray diffraction (8 m). A preliminary structure-activity relationship suggested that the presence of 1H-1,2,3-triazole ring in (R)-4-fluorophenyl-1H-1,2,3-triazole derivatives has remarkable contribution in the overall activity. Molecular docking studies were carried out to investigate the binding mode of compounds within the active site of the α-glucosidase enzyme. Docking results are in complete agreement with the experimental finding. This study unravelled a new class of triazole derivatives with α-glucosidase inhibitory activity.


Assuntos
Inibidores de Glicosídeo Hidrolases/síntese química , Inibidores de Glicosídeo Hidrolases/farmacologia , Triazóis/química , alfa-Glucosidases/química , Desenho de Fármacos , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade
8.
Bioorg Chem ; 81: 98-106, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30118991

RESUMO

Inhibition of α-glucosidase is an effective strategy for controlling the post-prandial hyperglycemia in diabetic patients. For the identification of new inhibitors of this enzyme, a series of new (R)-1-(2-(4-bromo-2-methoxyphenoxy) propyl)-4-(4-(trifluoromethyl) phenyl)-1H-1,2,3-triazole derivatives were synthesized (8a-d and 10a-e). The structures were confirmed by NMR, mass spectrometry and, in case of compound 8a, by single crystal X-ray crystallography. The α-glucosidase inhibitory activities were investigated in vitro. Most derivatives exhibited significant inhibitory activity against α-glucosidase enzyme. Their structure-activity relationship and molecular docking studies were performed to elucidate the active pharmacophore against this enzyme. Compound 10b was the most active analogue with IC50 value of 14.2 µM, while compound 6 was found to be the least active having 218.1 µM. A preliminary structure-activity relationship suggested that the presence of 1H-1,2,3-triazole ring in 1H-1,2,3-triazole derivatives is responsible for this activity and can be used as anti-diabetic drugs. The molecular docking studies of all active compounds were performed, in order to understand the mode of binding interaction and the energy of this class of compounds.


Assuntos
Simulação de Acoplamento Molecular , Triazóis/farmacologia , alfa-Glucosidases/metabolismo , Relação Dose-Resposta a Droga , Inibidores de Glicosídeo Hidrolases , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Triazóis/síntese química , Triazóis/química
9.
J Foot Ankle Surg ; 55(5): 1035-7, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26277240

RESUMO

A 35-year-old male presented with pain and swelling of his right foot and ankle. His pain developed gradually and without overt pedal deformity. The radiologic examination revealed complete fusion of all tarsal bones of his right foot. Comparative radiographs of his left foot also showed complete tarsal coalition. Ankle osteoarthritis was diagnosed, and supportive treatment enabled the patient to return to an asymptomatic status and continue the duties of his employment. This case is presented to describe an adult patient with bilateral, massive tarsal coalition who was essentially asymptomatic until degenerative arthritic changes developed in one of his ankles.


Assuntos
Diclofenaco/uso terapêutico , Terapia por Exercício/métodos , Coalizão Tarsal/diagnóstico por imagem , Coalizão Tarsal/terapia , Adulto , Terapia Combinada , Seguimentos , Deformidades Congênitas do Pé/diagnóstico por imagem , Deformidades Congênitas do Pé/terapia , Humanos , Masculino , Medição da Dor , Radiografia/métodos , Medição de Risco , Índice de Gravidade de Doença , Resultado do Tratamento
10.
J Perioper Pract ; 34(6): 199-203, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38343376

RESUMO

BACKGROUND: Patients undergoing major gastrointestinal (GI) surgery including hepato-pancreato-biliary (HPB) surgeries have large incisions, which cause severe acute postoperative pain that, if untreated, is associated with a higher incidence of postoperative morbidity and delayed recovery. METHODOLOGY: Our study included all patients who underwent elective major upper GI and HPB surgeries from 1 January 2018 to 31 December 2018. The patients were divided into two groups: the epidural and the non-epidural group. The average and worst pain scores at rest and movement were compared between both groups. We also studied the effect of pain relief in the two groups and associated postoperative outcomes, resumption of feeding, ambulation, hospital stay and intensive care unit stay. RESULTS: A total of 566 patients were included in the study, out of which 490 received epidurals, and the rest, 76, belonged to the non-epidural group (transversus abdominis plane, rectus sheath block or no regional analgesia technique). The median average pain score at rest and movement was 2.0 and 3.0, respectively, in the epidural and non-epidural groups. The postoperative outcomes showed no statistical difference. CONCLUSION: The epidural group and the non-epidural group had similar pain scores, and the postoperative outcomes were also comparable.


Assuntos
Manejo da Dor , Dor Pós-Operatória , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Manejo da Dor/métodos , Idoso , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Analgesia Epidural/efeitos adversos , Medição da Dor , Adulto
11.
J Biomol Struct Dyn ; : 1-21, 2024 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-38433423

RESUMO

In the current study, metronidazole derivatives containing 1H-1,2,3-triazole and carboxylate moieties were evaluated in vitro and by computational methods for their anti-diabetic potential to insight into their medicinal use for the management of type II diabetes mellitus. Interestingly all 14 compounds displayed high to significant inhibitory capability against the key carbohydrate's digestive enzyme α-glucosidase with IC50 values in range of 9.73-56.39 µM, as compared to marketed drug acarbose (IC50 = 873.34 ± 1.67 µM). Compounds 5i and 7c exhibited the highest inhibition, therefore, these two compounds were further evaluated for their mechanistic studies to explore its type of inhibition. Compounds 5i and 7c both displayed a concentration-dependent (competitive type of inhibition) with Ki values 7.14 ± 0.01, 6.15 ± 0.02 µM, respectively, which conclude their favourable interactions with the active site residues of the α-glucosidase. Interestingly all compounds are non-cytotoxic against BJ cell line. To further validate our findings, in-silico approaches like molecular docking, and molecular dynamic simulations were applied to investigate the mode of bindings of compounds with the enzyme and identifies their inhibition mechanism, which strongly complements our experimental findings.Communicated by Ramaswamy H. Sarma.

12.
Artigo em Inglês | MEDLINE | ID: mdl-38500715

RESUMO

Objective: The study examined resources needed by Infection Preventionists (IP) to address infection prevention and control (IPC) program gaps. Design: A 49-question survey. Setting: Licensed Critical Access Hospitals (CAHs) in Federal Emergency Management Area (FEMA) Region VII. Participants: IP at licensed CAHs. Methods: The survey conducted between December 2020 and January 2021 consisted of questions focusing on four categories including IPC program infrastructure, competency-based training, audit and feedback, and identification of high-risk pathogens/serious communicable diseases (HRP/SCD). An IPC score was calculated for each facility by totaling "Yes" responses (which indicate best practices) to 49 main survey questions. Follow-up questions explored the resources needed by the CAHs to implement or further strengthen best practices and mitigate IPC practice gaps. Welch t-test was used to study differences in IPC practice scores between states. Results: 50 of 259 (19.3%) CAHs participated in the survey with 37 (14.3%) answering all 49 questions. CAHs responding to all questions had a median IPC score of 35. There was no significant difference between IPC practice scores of CAHs in NE and IA. The top three IPC gaps were absence of drug diversion program (77%), lack of audits and feedback for insertion and maintenance of central venous catheters (76%), and missing laboratory risk assessments to identify tests that can be offered safely for patients under investigation for HRP/SCD (76%). Standardized audit tools, educational resources, and staff training materials were cited as much-needed resources. Conclusion: IPC practice gaps exist in CAHs. Various resources are needed for gap mitigation.

13.
Curr Med Chem ; 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38333973

RESUMO

Tumor diseases remain among the world's primary causes of death despite substantial advances in cancer diagnosis and treatment. The adverse chemotherapy problems and sensitivity towards drugs for some cancer types are among the most promising challenges in modern treatment. Finding new anti-cancer agents and drugs is, therefore, essential. A significant class of biologically active substances and prospective medications against cancer is comprised of bacterial proteins and peptides. Among these bacterial peptides, some of them, such as anti-cancer antibiotics and many toxins like diphtheria are widely being used in the treatment of cancer. In contrast, the remaining bacterial peptides are either in clinical trials or under research in vitro studies. This study includes the most recent information on the characteristics and mechanism of action of the bacterial peptides that have anti-cancer activities, some of which are now being employed in cancer therapy while some are still undergoing research.

14.
J Biomol Struct Dyn ; : 1-16, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38294707

RESUMO

Present research was designed to synthesize and characterize the flurbiprofen derivatives and to evaluate their analgesic, anti-inflammatory and gastro-protective activities in post-operative and chronic inflammatory pain models. Flurbiprofen derivatives were produced by using three-step processes involving esterification, hydrazide production, and schiff base, each of which modified a different carboxyl group. All the newly synthesized flurbiprofen derivatives (NS5-NS8) were characterized by 1H NMR,13C NMR,19F NMR and HR-ESI-MS, and the post-operative, inflammatory pain and ulcerogenic activities were determined in well-established in-vivo animal models. To evaluate post-operative and inflammatory pain, various doses of compounds [1, 3, 10, and 30 mg/kg (bwt)] were used, while their ulcerogenic potential was assessed at doses of 100 and 150 mg/kg (bwt). The incisional damage linked pain was significantly (p < 0.001) reduced by derivatives at different doses in both the acute and repeated tests with decreased response of phologistic agent-induced inflammation. The stomach histology and biochemical features demonstrate that the synthesized derivatives have no potential to cause ulcerogenicity as compared to aspirin and flurbiprofen. Furthermore, docking shows that the hydrazide moiety of these compounds is crucial in interacting within COX-2 binding site. Therefore, the synthesized compounds exhibit strong analgesic and anti-inflammatory effects and a low risk of causing ulcers. These attributes render them potentially valuable therapeutic agents for the treatment of pathological disorders associated with inflammation and pain.Communicated by Ramaswamy H. Sarma.

15.
Sci Rep ; 14(1): 3590, 2024 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-38351259

RESUMO

COVID-19 appeared as a highly contagious disease after its outbreak in December 2019 by the virus, named SARS-CoV-2. The threat, which originated in Wuhan, China, swiftly became an international emergency. Among different genomic products, spike protein of virus plays a crucial role in the initiation of the infection by binding to the human lung cells, therefore, SARS-CoV-2's spike protein is a promising therapeutic target. Using a combination of a structure-based virtual screening and biochemical assay, this study seeks possible therapeutic candidates that specifically target the viral spike protein. A database of ~ 850 naturally derived compounds was screened against SARS-CoV-2 spike protein to find natural inhibitors. Using virtual screening and inhibitory experiments, we identified acetyl 11-keto-boswellic acid (AKBA) as a promising molecule for spike protein, which encouraged us to scan the rest of AKBA derivatives in our in-house database via 2D-similarity searching. Later 19 compounds with > 85% similarity with AKBA were selected and docked with receptor binding domain (RBD) of spike protein. Those hits declared significant interactions at the RBD interface, best possess and excellent drug-likeness and pharmacokinetics properties with high gastrointestinal absorption (GIA) without toxicity and allergenicity. Our in-silico observations were eventually validated by in vitro bioassay, interestingly, 10 compounds (A3, A4, C3, C6A, C6B, C6C, C6E, C6H, C6I, and C6J) displayed significant inhibitory ability with good percent inhibition (range: > 72-90). The compounds C3 (90.00%), C6E (91.00%), C6C (87.20%), and C6D (86.23%) demonstrated excellent anti-SARS CoV-2 spike protein activities. The docking interaction of high percent inhibition of inhibitor compounds C3 and C6E was confirmed by MD Simulation. In the molecular dynamics simulation, we observed the stable dynamics of spike protein inhibitor complexes and the influence of inhibitor binding on the protein's conformational arrangements. The binding free energy ΔGTOTAL of C3 (-38.0 ± 0.08 kcal/mol) and C6E (-41.98 ± 0.08 kcal/mol) respectively indicate a strong binding affinity to Spike protein active pocket. These findings demonstrate that these molecules particularly inhibit the function of spike protein and, therefore have the potential to be evaluated as drug candidates against SARS-CoV-2.


Assuntos
COVID-19 , Humanos , Farmacóforo , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Simulação de Dinâmica Molecular , Simulação de Acoplamento Molecular
16.
ACS Omega ; 8(28): 24901-24911, 2023 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-37483205

RESUMO

A series of novel alkyl derivatives (2-5a,b) and 1H-1,2,3-triazole analogues (7a-k) of Meldrum's acid were synthesized in a highly effective way by using "click" chemistry and screened for in vitro α-glucosidase inhibitory activity to examine their antidiabetic potential. 1H NMR, 13C-NMR, and high-resolution electrospray ionization mass spectra (HR-ESI-MS) were used to analyze each of the newly synthesized compounds. Interestingly, these compounds demonstrated high to moderate α-glucosidase inhibitory potency having an IC50 range of 4.63-80.21 µM. Among these derivatives, compound 7i showed extraordinary inhibitory activity and was discovered to be several times more potent than the parent compound Meldrum (1) and the standard drug acarbose. Later, molecular docking was performed to understand the binding mode and the binding strength of all the compounds with the target enzyme, which revealed that all compounds are well fitted in the active site of α-glucosidase. To further ascertain the structure of compounds, suitable X-ray single crystals of compounds 5a, 7a, and 7h were developed and studied. The current investigation has shown that combining 1H-1,2,3-triazole with the Meldrum moiety is beneficial. Furthermore, this is the first time that the aforementioned activity of these compounds has been reported.

17.
RSC Adv ; 13(18): 12518-12528, 2023 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-37091596

RESUMO

The discovery of post-operative, chronic inflammatory pain and any gastroulcerogenic potential using well-established animal models in vivo with new structures, high efficiency, broad-spectrum, and low toxicity has been the focus of medicinal chemists. In the present article, we are reporting the design and synthesis of various derivatives of ibuprofen by modifying the carboxyl group of ibuprofen using three steps reactions; esterification under microwave-irradiation in 10 minutes, hydrazide formation, and finally schiff's base reaction. Microwave-assisted esterification reaction can be employed to quickly explore and increase molecular diversity in synthetic chemistry. All of the newly synthesized compounds (NS1-NS4) were characterized by 1H-, 13C-NMR, and HR-ESI-MS spectroscopy and evaluated for post-operative, chronic inflammatory pain and any gastroulcerogenic potential using well-established animal models in vivo. The synthesized compounds at the tested doses of 100 and 150 mg kg-1 significantly attenuated the incisional-injury induced post-operative pain like condition and, also inhibited the phologistic agent induced inflammatory responses in both the acute and chronic testing paradigms. The gastric histological and biochemical parameters exhibited that the synthesized compounds were devoid of any ulcerogenic potential in comparison to aspirin and ibuprofen. These findings concluded that the synthesized ibuprofen derivatives exhibited profound analgesic, anti-inflammatory properties with reduced ulcerogenic potential and might be considered as effective therapeutic agents to treat pathological conditions associated with pain and inflammation.

18.
Pharmaceuticals (Basel) ; 16(2)2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-37259377

RESUMO

A series of 24 new 1H-1,2,3-triazole hybrids of 3-O-acetyl-11-keto-ß-boswellic acid (ß-AKBA (1)) and 11-keto-ß-boswellic acid (ß-KBA (2)) was designed and synthesized by employing "click" chemistry in a highly efficient manner. The 1,3-dipolar cycloaddition reaction between ß-AKBA-propargyl ester intermediate 3 or ß-KBA-propargyl ester intermediate 4 with substituted aromatic azides 5a-5k in the presence of copper iodide (CuI) and Hünig's base furnished the desired products-1H-1,2,3-triazole hybrids of ß-AKBA (6a-6k) and ß-KBA (7a-7k)-in high yields. All new synthesized compounds were characterized by 1H-, 13C-NMR spectroscopy, and HR-ESI-MS spectrometry. Furthermore, their α-glucosidase-inhibitory activity was evaluated in vitro. Interestingly, the results obtained from the α-glucosidase-inhibitory assay revealed that all the synthesized derivatives are highly potent inhibitors, with IC50 values ranging from 0.22 to 5.32 µM. Among all the compounds, 6f, 7h, 6j, 6h, 6g, 6c, 6k, 7g, and 7k exhibited exceptional inhibitory potency and were found to be several times more potent than the parent compounds 1 and 2, as well as standard acarbose. Kinetic studies of compounds 6g and 7h exhibited competitive and mixed types of inhibition, with ki values of 0.84 ± 0.007 and 1.18 ± 0.0012 µM, respectively. Molecular docking was carried out to investigate the binding modes of these compounds with α-glucosidase. The molecular docking interactions indicated that that all compounds are well fitted in the active site of α-glucosidase, where His280, Gln279, Asp215, His351, Arg442, and Arg315 mainly stabilize the binding of these compounds. The current study demonstrates the usefulness of incorporating a 1H-1,2,3-triazole moiety into the medicinally fascinating boswellic acids skeleton.

19.
Anticancer Agents Med Chem ; 22(19): 3208-3218, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34749628

RESUMO

Cancer is a leading cause of death worldwide. Proper efficient drugs are required to treat this deadly disease. Natural products have long been a vital source of anticancer agents and they have generated various "lead compounds" suitable for drug developments. With the recent advancement of chemical synthesis and bioevaluation techniques, these lead compounds of natural origins have been utilized for the production of useful anticancer drugs. Among the naturally occurring bioactive compounds, various O-heterocycles have been evaluated as remarkable cancer therapeutic agents. These compounds generally possess unique structures and novel mechanisms of action. In the present review article, some selected O-heterocycles as promoting anticancer agents have been discussed in brief. Various natural sources and chemistry, as well as bioactivities of these compounds, have been described. The development of improved analogues of these compounds through synthetic modifications and efficient bioevaluation, along with proper studies on structure-activity relationship and mechanism of actions, has been mentioned. The article has demonstrated the recent relevance of naturally occurring O-heterocyclic compounds in the current anticancer drug discovery and development scenario.


Assuntos
Antineoplásicos , Produtos Biológicos , Compostos Heterocíclicos , Neoplasias , Antineoplásicos/química , Produtos Biológicos/química , Compostos Heterocíclicos/química , Humanos , Neoplasias/tratamento farmacológico , Relação Estrutura-Atividade
20.
PLoS One ; 17(10): e0275148, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36190972

RESUMO

Cyanobacteria are prokaryotic Gram-negative organisms prevalent in nearly all habitats. A detailed proteomics study of Cyanobacteria has not been conducted despite extensive study of their genome sequences. Therefore, we conducted a proteome-wide analysis of the Cyanobacteria proteome and found Calothrix desertica as the largest (680331.825 kDa) and Candidatus synechococcus spongiarum as the smallest (42726.77 kDa) proteome of the cyanobacterial kingdom. A Cyanobacterial proteome encodes 312.018 amino acids per protein, with a molecular weight of 182173.1324 kDa per proteome. The isoelectric point (pI) of the Cyanobacterial proteome ranges from 2.13 to 13.32. It was found that the Cyanobacterial proteome encodes a greater number of acidic-pI proteins, and their average pI is 6.437. The proteins with higher pI are likely to contain repetitive amino acids. A virtual 2D map of Cyanobacterial proteome showed a bimodal distribution of molecular weight and pI. Several proteins within the Cyanobacterial proteome were found to encode Selenocysteine (Sec) amino acid, while Pyrrolysine amino acids were not detected. The study can enable us to generate a high-resolution cell map to monitor proteomic dynamics. Through this computational analysis, we can gain a better understanding of the bias in codon usage by analyzing the amino acid composition of the Cyanobacterial proteome.


Assuntos
Proteoma , Synechococcus , Ponto Isoelétrico , Proteoma/metabolismo , Proteômica , Selenocisteína , Synechococcus/genética , Synechococcus/metabolismo
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