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1.
Molecules ; 24(18)2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31491967

RESUMO

Alzheimer's disease (AD) is a widespread dynamic neurodegenerative malady. Its etiology is still not clear. One of the foremost pathological features is the extracellular deposits of Amyloid-beta (Aß) peptides in senile plaques. The interaction of Aß and the receptor for advanced glycation end products at the blood-brain barrier is also observed in AD, which not only causes the neurovascular anxiety and articulation of proinflammatory cytokines, but also directs reduction of cerebral bloodstream by upgrading the emission of endothelin-1 to induce vasoconstriction. In this process, RAGE is deemed responsible for the influx of Aß into the brain through BBB. In the current study, we predicted the interaction potential of the natural compounds vincamine, ajmalicine and emetine with the Aß peptide concerned in the treatment of AD against the standard control, curcumin, to validate the Aß peptide-compounds results. Protein-protein interaction studies have also been carried out to see their potential to inhibit the binding process of Aß and RAGE. Moreover, the current study verifies that ligands are more capable inhibitors of a selected target compared to positive control with reference to ΔG values. The inhibition of Aß and its interaction with RAGE may be valuable in proposing the next round of lead compounds for effective Alzheimer's disease treatment.


Assuntos
Peptídeos beta-Amiloides/química , Produtos Biológicos/química , Modelos Moleculares , Doença de Alzheimer , Aminoácidos , Peptídeos beta-Amiloides/antagonistas & inibidores , Peptídeos beta-Amiloides/metabolismo , Proteínas Amiloidogênicas/antagonistas & inibidores , Proteínas Amiloidogênicas/química , Sítios de Ligação , Produtos Biológicos/farmacologia , Humanos , Ligações de Hidrogênio , Ligantes , Conformação Molecular , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Ligação Proteica , Relação Estrutura-Atividade
2.
Ecotoxicol Environ Saf ; 176: 108-118, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-30925326

RESUMO

Rhizospheric and plant root associated microbes generally play a protective role against arsenic toxicity in rhizosphere. Rhizospheric microbial interaction influences arsenic (As) detoxification/mobilization into crop plants and its level of toxicity and burden. In the present investigation, we have reported a rhizospheric fungi Aspergillus flavus from an As contaminated rice field, which has capability to grow at high As concentration and convert soluble As into As particles. These As particles showed a reduced toxicity to soil dwelling bacteria, fungi, plant and slime mold. It does not disrupt membrane potential, inner/outer membrane integrity and survival of the free N2 fixating bacteria. In arbuscular mycorrhiza like endophytic fungi Piriformospora indica, these As particles does not influence mycelial growth and plant beneficial parameters such as phosphate solubilizing enzyme rAPase secretion and plant root colonization. Similarly, it does not affect plant growth and chlorophyll content negatively in rice plant. However, these As particles showed a poor absorption and mobilization in plant. These As particle also does not affect attachment process and survival of amoeboid cells in slime mold, Dictyostelium discoideum. This study suggests that the process of conversion of physical and chemical properties of arsenic during transformation, decides the toxicity of arsenic particles in the rhizospheric environment. This phenomenon is of environmental significance, not only in reducing arsenic toxicity but also in the survival of healthy living organism in arsenic-contaminated rhizospheric environment.


Assuntos
Arsênico/metabolismo , Arsênico/toxicidade , Microbiota/efeitos dos fármacos , Micorrizas/metabolismo , Oryza/metabolismo , Microbiologia do Solo , Aspergillus flavus/metabolismo , Biotransformação , Oryza/crescimento & desenvolvimento , Oryza/microbiologia , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Raízes de Plantas/microbiologia , Rizosfera , Solo/química , Poluentes do Solo/metabolismo , Poluentes do Solo/toxicidade
3.
Curr Comput Aided Drug Des ; 15(3): 265-276, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30706824

RESUMO

INTRODUCTION: The regulation of apoptosis via compounds originated from marine organisms signifies a new wave in the field of drug discovery. Marine organisms produce potent compounds as they hold the phenomenal diversity in chemical structures. The main focus of drug development is anticancer therapy. METHODS: Expertise on manifold activities of compounds helps in the discovery of their derivatives for preclinical and clinical experiment that promotes improved activity of compounds for cancer patients. RESULTS: These marine derived compounds stimulate apoptosis in cancer cells by targeting Bcl-2 and Survivin, highlighting the fact that instantaneous targeting of these proteins by novel derivatives results in efficacious and selective killing of cancer cells. CONCLUSION: Our study reports the identification of Aplysin and Haterumaimide J as Bcl-2 inhibitors and Cortistatin A as an inhibitor of survivin protein, from a sequential virtual screening approach.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Organismos Aquáticos/química , Proteínas Proto-Oncogênicas c-bcl-2/química , Survivina/química , Survivina/farmacologia , Animais , Descoberta de Drogas , Ensaios de Seleção de Medicamentos Antitumorais , Simulação de Acoplamento Molecular , Terapia de Alvo Molecular , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Survivina/síntese química
4.
J Diet Suppl ; 16(4): 470-490, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29580105

RESUMO

Diabetic neuropathy is a chronic complication of diabetes mellitus affecting about 50% of patients. Its symptoms include decreased motility and severe pain in peripheral parts. The pathogenesis involved is an abnormality in blood vessels that supply the peripheral nerves, metabolic disorders such as myo-inositol depletion, and increased nonenzymatic glycation. Moreover, oxidative stress in neurons results in activation of multiple biochemical pathways, which results in the generation of free radicals. Apart from available marketed formulations, extensive research is being carried out on herbal-based natural products to control hyperglycemia and its associated complications. This review is focused to provide a summary on diabetic neuropathy covering its etiology, types, and existing work on herbal-based therapies, which include pure compounds isolated from plant materials, plant extracts, and Ayurvedic preparations.


Assuntos
Neuropatias Diabéticas/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Animais , Neuropatias Diabéticas/etiologia , Neuropatias Diabéticas/fisiopatologia , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Hiperglicemia/tratamento farmacológico , Medicina Ayurvédica , Estresse Oxidativo , Fitoterapia
5.
Saudi J Biol Sci ; 25(8): 1546-1551, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30581316

RESUMO

Japanese encephalitis (JE), a viral disease has seen a drastic and fatal enlargement in the northern states of India in the current decade. The better and exact cure for the disease is still in waiting. For the cause an in silico strategy in the development of the peptide vaccine has been taken here for the study. A computational approach to find out the Major Histocompatibility Complex (MHC) binding peptide has been implemented. The prediction analysis identified MHC class I (using propred I) and MHC class II (using propred) binding peptides at an expectable percent predicted IC (50) threshold values. These predicted Human leukocyte antigen [HLA] allele binding peptides were further analyzed for potential conserved region using an Immune Epitope Database and Analysis Resource (IEDB). This analysis shows that HLA-DRB1*0101, HLA-DRB3*0101, HLA-DRB1*0401, HLA-DRB1*0102 and HLA-DRB1*07:01% of class II (in genotype 2) and HLA-A*0101, HLA-A*02, HLA-A*0301, HLA-A*2402, HLA-B*0702 and HLA-B*4402% of HLA I (in genotype 3) bound peptides are conserved. The predicted peptides MHC class I are ILDSNGDIIGLY, FVMDEAHFTDPA, KTRKILPQIIK, RLMSPNRVPNYNLF, APTRVVAAEMAEAL, YENVFHTLW and MHC class II molecule are TTGVYRIMARGILGT, NYNLFVMDEAHFTDP, AAAIFMTATPPGTTD, GDTTTGVYRIMARGI and FGEVGAVSL found to be top ranking with potential super antigenic property by binding to all HLA. Out of these the predicted peptide FVMDEAHFTDPA for allele HLA-A*02:01 in MHC class I and NYNLFVMDEAHFTDP for allele HLA-DRB3*01:01 in MHC class II was observed to be most potent and can be further proposed as a significant vaccine in the process. The reported results revealed that the immune-informatics techniques implemented in the development of small size peptide is useful in the development of vaccines against the Japanese encephalitis virus (JEV).

6.
Comput Biol Chem ; 77: 390-401, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30469054

RESUMO

The B-cell lymphoma-2 (Bcl-2) family proteins have been attributed to be the key regulators in programmed cell death and apoptosis with a prominent role in human cancer. Understanding the fundamental principles of cell survival and death have been the main cornerstone in cancer drug discovery for identification of novel anticancer agents. In this context the Bcl-2 family of anti-and pro-apoptotic proteins provide an excellent opportunity for development of anticancer agents, as blocking the Bcl-2 or Bcl-XL functionally promotes apoptosis in tumor cells and also sensitize them to chemo- and radiotherapies. The present study reports the identification of novel Aplysin analogs as BCL-2 inhibitors from a sequential virtual screening approach using drug-like, ADMET, docking, pharmacophore filters and molecular dynamics simulation. We identified promising Aplysin analogs that have a potential to be Bcl-2 inhibitors just like the standard drug Obatoclax. One of the compound analog 11 was identified to be a promising inhibitor of Bcl-2 in the docking, pharmacophore and simulation based models.The molecular modeling information provided here can be vital in designing of the novel Bcl-2 inhibitors.


Assuntos
Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Hidrocarbonetos Bromados/química , Hidrocarbonetos Bromados/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Apoptose/efeitos dos fármacos , Projeto Auxiliado por Computador , Desenho de Drogas , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
7.
Curr Drug Metab ; 19(6): 523-543, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28228080

RESUMO

BACKGROUND: Malignant tumors are the leading cause of death in humans. Due to the tedious efforts and investigations made in the field of marine drug discovery, there is now a scientific bridge between marine and pharmaceutical sciences. However, currently only few marine drugs have been lined towards anticancer direction yet many more to are be established in future as well. METHOD: This review gives an overview of present status of marine natural products MNPs both at the level of research and clinical stages. The authors haved summarized the detail information of diverse marine organisms that were reportedto be active or potentially active in cancer treatment in the last two decades. Interstingly, marine organisms are abundant producer of plenty of structurally incomparable bioactive metabolites that have unusual mode of actions and diverse biosynthetic pathways. RESULTS: This review summarizes the associated anticancer properties of different classes of marine natural compounds based on their structural diversity, biological activity, and the molecular mechanisms of action. Emphasis has also be given to recent advances in clinical development of marine agents used in clinical trials. CONCLUSIONS: The present review is summarising the various sources of marine chemicals and their exploration of anticancerous potential. There is justified hope for the discovery and development of new anticancer agents from the marine environment.


Assuntos
Antineoplásicos , Organismos Aquáticos , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Humanos , Neoplasias/tratamento farmacológico
8.
Bioinformation ; 13(9): 293-300, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29081608

RESUMO

Survivin (IAP proteins) remains an important target for anticancer drug development as it is reported to be over-expressed in tumor cells to enhance resistance to apoptotic stimuli. The study focuses on virtual screening of marine compounds inhibiting survivin, a multifunctional protein, using a computational approach. Structures of compounds were prepared using ChemDraw Ultra 10. Software and converted into its 3D PDB structure and its energy was minimized using Discovery Studio client 2.5. The target protein, survivin was retrieved from RCSB PDB. Lipinski's rule and ADMET toxicity profiling was carried out on marine compounds and the filtered compounds were further promoted for molecular docking analysis and interaction studies using AutoDock Tools 4.0. Molecular docking results revealed that analog (AP 4) of Aplysin, showed very promising inhibitory potential against survivin with a binding energy of -8.75 kcal/mol and Ki 388.28 nM as compared to its known inhibitor, Celecoxib having binding energy of -6.65 kcal/mol and Ki 13.43 µM. AP 4. The analog depicted similarity in pattern when compared to standard. The result proposes AP 4, is an effective molecule exhibiting prominent potential to inhibit survivin and thus promoting apoptosis in tumor cells.

9.
Curr Comput Aided Drug Des ; 13(4): 311-318, 2017 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-28413992

RESUMO

BACKGROUND: The present study clarifies the molecular interactions of human BACE1 with novel natural ligands and also with the well-known ligand 2, 2, 4-trihydroxychalcone and Galangin for comparison. OBJECTIVE: The study of enzyme- ligands interaction is interesting, thus description of ligands binding to the active site of target molecule could be beneficial for better understanding the mechanism of the ligand on the target molecule. METHODS: Lipinski rule of five and docking study were performed between ligands and enzyme using 'Autodock4.2'. RESULTS: It was found that hydrogen bond interactions play a significant role in the accurate positioning of ligands within the 'active site' of BACE1 to permit docking. Such information may aid to propose the BACE1 -inhibitors and is estimated to aid in the safe medical use of ligands. Selected ligands of BACE1 also inhibit the aggregated amyloid beta peptide. The aggregation of amyloid peptides Aß1-42 may be responsible for AD. CONCLUSION: Scope lies in the determination of the 3-dimensional structure of BACE1 and ligands complex by X-ray crystallography to certify the explained data. To validate the enzyme -ligands results, we considered 2, 2, 4-trihydroxychalconeas and Galangin as a positive control. Moreover, the current study verifies that ligands are more capable inhibitors of human BACE1 compared to positive control with reference to ΔG values.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Ácido Aspártico Endopeptidases/antagonistas & inibidores , Descoberta de Drogas/métodos , Inibidores de Proteases/química , Inibidores de Proteases/farmacologia , Doença de Alzheimer/enzimologia , Doença de Alzheimer/metabolismo , Secretases da Proteína Precursora do Amiloide/química , Secretases da Proteína Precursora do Amiloide/metabolismo , Peptídeos beta-Amiloides/metabolismo , Ácido Aspártico Endopeptidases/química , Ácido Aspártico Endopeptidases/metabolismo , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Domínio Catalítico , Chalconas/química , Chalconas/farmacologia , Cristalografia por Raios X , Flavonoides/química , Flavonoides/farmacologia , Humanos , Ligações de Hidrogênio , Ligantes , Simulação de Acoplamento Molecular , Agregados Proteicos/efeitos dos fármacos , Conformação Proteica , Termodinâmica
10.
Curr Drug Metab ; 18(1): 30-38, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27842486

RESUMO

BACKGROUND: Lung cancer is one of the most fatal chronic diseases in the field of respiratory medicine. The purpose of this paper is to address the side effects of conventional treatment strategies and to report the findings of till date drug nanocarriers researches performed for lung cancer therapy. This review also highlights the outstanding results of several researches employing pulmonary delivery system of nano-based drug formulations suitable for lung cancer. OBJECTIVE: Summarizing the advances made in the field of nanotechnology-based lung cancer management. METHODS: We systematically searched for research literature using a well-framed review question and presented data in the tabular forms for readers' convenience. RESULTS: Sixty-four papers were included in the review, the majority of which represent latest researches in the field of nanoparticle-based drug delivery for lung cancer therapy. Conventional treatment strategies for lung cancer lack specificity and are limited by undesirable toxicities in normal cells, as well as a high rate of recurrence. Intervention of nanotechnology has revolutionized the therapy of lung cancer upto a great extent by overcoming the current constraints in conventional therapies. Pulmonary delivery of nano-based drug formulations has resulted in potentially more effective and advanced lung cancer therapy. CONCLUSION: Several nanoscale drug delivery systems for lung cancer treatment are at present in clinical trials and some of them already exist in commercially available forms in the marketplace. However, although nanoscale drug carriers for lung cancer treatment have demonstrated stupendous therapeutic potential at both preclinical and clinical trials, but there are still many limitations to be solved.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Neoplasias Pulmonares/terapia , Nanotecnologia , Portadores de Fármacos , Humanos , Nanopartículas/administração & dosagem
11.
CNS Neurol Disord Drug Targets ; 15(10): 1279-1289, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27712576

RESUMO

AD is a progressive and irreversible neurodegenerative disease and the most common cause of dementia in the elderly population. Βeta- amyloid cascade formation along with several cytoskeleton abnormalities succeeding to the hyperphosphorylation of microtubule-associated tau protein in neurons leads to the elicitation of several neurotoxic incidents. As an outcome of these phenomena, steady growth of dementia in aged population is becoming ubiquitous in both developed and developing countries. Thus, the key aspiration is to endow with stable daily life functionality to the person suffering from dementia and to cut down or slower the symptoms of disease leading to disruptive behavior. In sight of this, the proteins amyloid-beta, BACE-1, RAGE and AChE are being aimed for the treatment of AD successfully. Currently, there are several medicines for the treatment of AD under survey like Galangin, Cymserine, Tolserine, Bisnorcymserine and Huperzine A. The article emphasizes clinical and neurobiological aspects of AD. The purpose of this review article is to provide a brief introduction of AD along with the related concept of beta-secretase, beta amyloid and neurotransmitter in the progression of disease. In the present review, we summarize the available evidence on the new therapeutic approaches that target amyloid and neurotransmitter in the AD.


Assuntos
Doença de Alzheimer/diagnóstico , Doença de Alzheimer/terapia , Gerenciamento Clínico , Acetilcolinesterase/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Ácido Aspártico Endopeptidases/metabolismo , Humanos , Receptor para Produtos Finais de Glicação Avançada/metabolismo
12.
Bioinformation ; 12(11): 400-407, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28293071

RESUMO

4-hydroxy-tetrahydrodipicolinate synthase (DHDPS) is an important enzyme needed for the biosynthesis of lysine and many more key metabolites in Mycobacterium tuberculosis (Mtb). Inhibition of DHDPS is supposed to a promising therapeutic target due to its specific role in sporulation, cross-linking of the peptidiglycan polymers and biosynthesis of amino acids. In this work, a known inhibitor-based similarity search was carried out against a natural products database (Super Natural II) towards identification of more potent phyto-inhibitors. Molecular interaction studies were accomplished using three different tools to understand and establish the participation of active site residues as the key players in stabilizing the binding mode of ligands and target protein. The best phyto-compound deduced on the basis of binding affinity was further used as a template to make similarity scan across the PubChem Compound database (score > = 80 %) to get more divesred leads. In this search 5098 hits were obtained that further reduced to 262 after drug-likeness filtration. These phytochemicallike compounds were docked at the active site of DHDPS.Then, those hits selected from docking analysis that showing stronger binding and forming maximum H-bonds with the active site residues (Thr54, Thr55, Tyr143, Arg148 and Lys171). Finally, we predicted one phytochemical compound (SN00003544), two PubChem-compounds (CID41032023, CID54025334) akin to phytochemical molecule showing better interactions in comaprison of known inhibitors of target protein.These findings might be further useful to gain the structural insight into the designing of novel leads against DapA family.

13.
Biotechnol Appl Biochem ; 63(4): 497-513, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25913286

RESUMO

We examined the interaction of polycyclic hydrocarbons (PAHs) like benzo-α-pyrene (BaP), chrysene, and their metabolites 7,8-dihydro-7,8-dihydroxybenzo(a)pyrene,9,10-oxide (BPDE) and chrysene 1,2-diol-3,4-epoxide-2 (CDE), with the enzymes involved in DNA repair. We investigated interaction of 120 enzymes with PAHs and screened out 40 probable targets among DNA repair enzymes, on the basis of higher binding energy than positive control. Out of which, 20 enzymes lose their function in the presence of BaP, chrysene, and their metabolites, which may fetter DNA repair pathways resulting in damage accumulation and finally leading to cancer formation. We propose the use of nanoparticles as a guardian against the PAH's induced toxicity. PAHs enter the cell via aryl hydrocarbon receptor (AHR). TiO2 NP showed a much higher docking score with AHR (12,074) as compared with BaP and chrysene with AHR (4,600 and 4,186, respectively), indicating a preferential binding of TiO2 NP with the AHR. Further, docking of BaP and chrysene with the TiO2 NP bound AHR complex revealed their strong adsorption on TiO2 NP itself, and not on their original binding site (at AHR). TiO2 NPs thereby prevent the entry of PAHs into the cell via AHR and hence protect cells against the deleterious effects induced by PAHs.


Assuntos
Benzopirenos/toxicidade , Crisenos/toxicidade , Biologia Computacional , Reparo do DNA/efeitos dos fármacos , Nanopartículas , Titânio/química , Titânio/farmacologia , Enzimas Reparadoras do DNA/química , Enzimas Reparadoras do DNA/metabolismo , Humanos , Modelos Moleculares , Conformação Molecular , Simulação de Acoplamento Molecular , Conformação Proteica , Titânio/metabolismo
14.
PLoS One ; 9(9): e107068, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25215666

RESUMO

Polycyclic aromatic hydrocarbons (PAH), like Benzo[alpha]Pyrene (BaP) are known to cause a number of toxic manifestations including lung cancer. As Titanium dioxide Nanoparticles (TiO2 NPs) have recently been shown to adsorb a number of PAHs from soil and water, we investigated whether TiO2 NPs could provide protection against the BaP induced toxicity in biological system. A549 cells when co-exposed with BaP (25 µM, 50 µM and 75 µM) along with 0.1 µg/ml,0.5 µg/ml and 1 µg/ml of TiO2 NPs, showed significant reduction in the toxic effects of BaP, as measured by Micronucleus Assay, MTT Assay and ROS Assay. In order to explore the mechanism of protection by TiO2 NP against BaP, we performed in silico studies. BaP and other PAHs are known to enter the cell via aromatic hydrocarbon receptor (AHR). TiO2 NP showed a much higher docking score with AHR (12074) as compared to the docking score of BaP with AHR (4600). This indicates a preferential binding of TiO2 NP with the AHR, in case if both the TiO2 NP and BaP are present. Further, we have done the docking of BaP with the TiO2 NP bound AHR-complex (score 4710), and observed that BaP showed strong adsorption on TiO2 NP itself, and not at its original binding site (at AHR). TiO2 NPs thereby prevent the entry of BaP in to the cell via AHR and hence protect cells against the deleterious effects induced by BaP.


Assuntos
Benzo(a)pireno/toxicidade , Carcinógenos Ambientais/toxicidade , Nanopartículas/química , Titânio/farmacologia , Sítios de Ligação , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Simulação por Computador , Endocitose/efeitos dos fármacos , Humanos , Testes para Micronúcleos , Simulação de Acoplamento Molecular , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Receptores de Hidrocarboneto Arílico/química , Receptores de Hidrocarboneto Arílico/metabolismo , Reprodutibilidade dos Testes , Software
15.
Pharmacogn Mag ; 10(37): 18-26, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24695379

RESUMO

BACKGROUND: In osteosarcoma tissue, both MMP-2 and MMP-9 are over expressed compared to their expression in non-affected stromal tissue. Hence, gelatinases are attractive targets for anti-osteosarcoma drugs. OBJECTIVE: To study the inhibitory activity of compounds isolated from Ageratum houstonianum against MMP-2 and MMP-9 by in-silico approach. MATERIAL AND METHODS: We performed docking study using 'Autodock 4.2' between 1,2-benzenedicarboxylic acid-bis (2-ethylhexyl) ester; squalene; 3,5-bis (1,1-dimethylethyl) phenol; pentamethyl tetrahydro-5H-chromene; (1, 4-cyclohexylphenyl) ethanone and 6-vinyl-7-methoxy-2,2-dimethylchromene with MMP-2 and MMP-9. RESULTS: Among all six compounds isolated from Ageratum houstonianum, (1, 4-cyclohexylphenyl) ethanone showed the maximum potential as a putative inhibitor of both MMP-2 and MMP-9 enzymes with reference to ΔG (-7.95 and -8.2 kcal/mol, respectively) and Ki (1.48 and 0.98 µM, respectively) values. Total intermolecular energy of docking for (1, 4-cyclohexylphenyl) ethanone-MMP catalytic domain-interaction was found to be -8.55 kcal/mol for MMP-2 and -9.21 kcal/mol for MMP-9. CONCLUSION: This study explores molecular interactions between human MMPs (MMP-2 and MMP-9) and six natural compounds. This study predicts that (1,4-cyclohexylphenyl) ethanone is a more efficient inhibitor of human MMP-2 and MMP-9 enzymes compared to the other natural compounds used in this study with reference to Ki and ΔG values.

16.
Indian J Exp Biol ; 51(3): 187-200, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23678539

RESUMO

Wireless technologies are ubiquitous today and the mobile phones are one of the prodigious output of this technology. Although the familiarization and dependency of mobile phones is growing at an alarming pace, the biological effects due to the exposure of radiations have become a subject of intense debate. The present evidence on mobile phone radiation exposure is based on scientific research and public policy initiative to give an overview of what is known of biological effects that occur at radiofrequency (RF)/ electromagnetic fields (EMFs) exposure. The conflict in conclusions is mainly because of difficulty in controlling the affecting parameters. Biological effects are dependent not only on the distance and size of the object (with respect to the object) but also on the environmental parameters. Health endpoints reported to be associated with RF include childhood leukemia, brain tumors, genotoxic effects, neurological effects and neurodegenerative diseases, immune system deregulation, allergic and inflammatory responses, infertility and some cardiovascular effects. Most of the reports conclude a reasonable suspicion of mobile phone risk that exists based on clear evidence of bio-effects which with prolonged exposures may reasonably be presumed to result in health impacts. The present study summarizes the public issue based on mobile phone radiation exposure and their biological effects. This review concludes that the regular and long term use of microwave devices (mobile phone, microwave oven) at domestic level can have negative impact upon biological system especially on brain. It also suggests that increased reactive oxygen species (ROS) play an important role by enhancing the effect of microwave radiations which may cause neurodegenerative diseases.


Assuntos
Encéfalo/efeitos da radiação , Telefone Celular , Animais , Apoptose , Biofísica/métodos , Neoplasias Encefálicas/etiologia , Ciclo Celular , Linhagem Celular Tumoral , Sistema Nervoso Central/efeitos da radiação , Dano ao DNA/efeitos da radiação , Campos Eletromagnéticos , Exposição Ambiental , Radicais Livres , Humanos , Camundongos , Modelos Biológicos , Mutagênicos , Neoplasias Induzidas por Radiação/diagnóstico , Radiometria , Ratos , Espécies Reativas de Oxigênio
17.
Cell Biochem Biophys ; 65(2): 85-96, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22926544

RESUMO

There are possible hazardous health effects of exposure to radiofrequency electromagnetic radiations emitted from mobile phone on the human reproductive pattern. It is more effective while keeping mobile phones in pocket or near testicular organs. Present review examines the possible concern on radio frequency radiation interaction and biological effects such as enzyme induction, and toxicological effects, including genotoxicity and carcinogenicity, testicular cancer, and reproductive outcomes. Testicular infertility or testicular cancer due to mobile phone or microwave radiations suggests an increased level of reactive oxygen species (ROS). Though generation of ROS in testis has been responsible for possible toxic effects on physiology of reproduction, the reviews of last few decades have well established that these radiations are very harmful and cause mutagenic changes in reproductive pattern and leads to infertility. The debate will be focused on bio-interaction mechanism between mobile phone and testicular cancer due to ROS formation. This causes the biological damage and leads to several changes like decreased sperm count, enzymatic and hormonal changes, DNA damage, and apoptosis formation. In the present review, physics of mobile phone including future research on various aspects has been discussed.


Assuntos
Telefone Celular , Campos Eletromagnéticos/efeitos adversos , Ondas de Rádio/efeitos adversos , Reprodução/efeitos da radiação , Humanos , Infertilidade Masculina/etiologia , Infertilidade Masculina/genética , Masculino , Mutagênese/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Oxigênio/efeitos da radiação , Reprodução/genética , Testículo/metabolismo , Testículo/efeitos da radiação
18.
Bioinformation ; 8(17): 795-800, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23139587

RESUMO

DNA damage occurs almost all the times in cells, but is repaired also continuously. Occurrence of all these mutations and their accumulation in one cell which finally becomes tumorigenic/carcinogenic appears possible if the DNA repair mechanism is hampered. We hypothesize that alterations in DNA repair pathways, either all or at least at one i.e. genetic, translational or posttranslational level, becomes quite imperative for the initiation and progression of Cancer. Therefore, we investigated the interaction capability of some carcinogens with the enzymes involved in the DNA repair mechanisms. Cigarette smoke's derivatives like NNK and NNAL are well established carcinogens. Hence, we analyzed 72 enzymes involved in the DNA repair Mechanisms for their interactions with ligands (NNK and NNAL). The binding efficiencies with enzymes ranging from +36.96 to -7.47 Kcal/Mol. Crystal Structure of Human Carbonmonoxy-Haemoglobin at 1.25 Å Resolution, PDB ID-1IRD as a +Ve control, showed binding energy -6.31 to -6.68 Kcal/Mol. and Human heat shock factor-binding protein 1, PDB ID- 3CI9 as a -Ve control, showed - 3.91 to +2.09 Kcal/Mol. Binding was characterized for the enzymes sharing equivalent or better interaction as compared to +Ve control. Study indicated the loss of functions of these enzymes, which probably could be a reason for fettering of DNA repair pathways resulting in damage accumulation and finally cancer formation.

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