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1.
J Asian Nat Prod Res ; : 1-24, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39078342

RESUMO

An imbalanced microbiome is linked to several diseases, such as cancer, inflammatory bowel disease, obesity, and even neurological disorders. Bacteria and their by-products are used for various industrial and clinical purposes. The metabolites under discussion were chosen based on their biological impacts on host and gut microbiota interactions as established by metabolome research. The separation of bacterial metabolites by using statistics and machine learning analysis creates new opportunities for applications of bacteria and their metabolites in the environmental and medical sciences. Thus, the metabolite production strategies, methodologies, and importance of bacterial metabolites for human well-being are discussed in this review.

2.
Molecules ; 29(3)2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38338420

RESUMO

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are enzymes that break down and reduce the level of the neurotransmitter acetylcholine (ACh). This can cause a variety of cognitive and neurological problems, including Alzheimer's disease. Taxifolin is a natural phytochemical generally found in yew tree bark and has significant pharmacological properties, such as being anti-cancer, anti-inflammatory, and antioxidant. The binding affinity and inhibitory potency of taxifolin to these enzymes were evaluated through molecular docking and molecular dynamics simulations followed by the MMPBSA approach, and the results were significant. Taxifolin's affinity for binding to the AChE-taxifolin complex was -8.85 kcal/mol, with an inhibition constant of 326.70 nM. It was observed to interact through hydrogen bonds. In contrast, the BChE-taxifolin complex binding energy was observed to be -7.42 kcal/mol, and it was significantly nearly equal to the standard inhibitor donepezil. The molecular dynamics and simulation signified the observed interactions of taxifolin with the studied enzymes. The MMPBSA total free energy of binding for AChE-taxifolin was -24.34 kcal/mol, while BChE-taxifolin was -16.14 kcal/mol. The present research suggests that taxifolin has a strong ability to bind and inhibit AChE and BChE and could be used to manage neuron-associated problems; however, further research is required to explore taxifolin's neurological therapeutic potential using animal models of Alzheimer's disease.


Assuntos
Acetilcolinesterase , Doença de Alzheimer , Quercetina/análogos & derivados , Animais , Acetilcolinesterase/metabolismo , Butirilcolinesterase/química , Doença de Alzheimer/tratamento farmacológico , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/uso terapêutico , Inibidores da Colinesterase/química , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade
3.
Pharmaceuticals (Basel) ; 16(3)2023 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-36986433

RESUMO

Indole-tethered chromene derivatives were synthesised in a one-pot multicomponent reaction using N-alkyl-1H-indole-3-carbaldehydes, 5,5-dimethylcyclohexane-1,3-dione, and malononitrile, catalysed by DBU at 60-65 °C in a short reaction time. The benefits of the methodology include non-toxicity, an uncomplicated set-up procedure, a faster reaction time, and high yields. Moreover, the anticancer properties of the synthesised compounds were tested against selected cancer cell lines. The derivatives 4c and 4d displayed very good cytotoxic activity, with IC50 values ranging from 7.9 to 9.1 µM. Molecular docking revealed the potent derivatives have good binding affinity towards tubulin protein, better than the control, and the molecular dynamic simulations further demonstrated the stability of ligand-receptor interactions. Moreover, the derivatives followed all the drug-likeness filters.

4.
Pharmaceuticals (Basel) ; 15(11)2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36355520

RESUMO

Anthraquinones (AQs) are present in foods, dietary supplements, pharmaceuticals, and traditional treatments and have a wide spectrum of pharmacological activities. In the search for anti-cancer drugs, AQ derivatives are an important class. In this study, anthraquinone aglycons chrysophanol (Chr), emodin (EM) and FDA-approved anticancer drug fluorouracil were analyzed by molecular docking studies against receptor molecules caspase-3, apoptosis regulator Bcl-2, TRAF2 and NCK-interacting protein kinase (TNIK) and cyclin-dependent protein kinase 2 (CDK2) as novel candidates for future anticancer therapeutic development. The ADMET SAR database was used to predict the toxicity profile and pharmacokinetics of the Chr and EM. Furthermore, in silico results were validated by the in vitro anticancer activity against HCT-116 and HeLa cell lines to determine the anticancer effect. According to the docking studies simulated by the docking program AutoDock Vina 4.0, Chr and EM had good binding energies against the target proteins. It has been observed that Chr and EM show stronger molecular interaction than that of the FDA-approved anticancer drug fluorouracil. In the in vitro results, Chr and EM demonstrated promising anticancer activity in HCT-116 and HeLa cells. These findings lay the groundwork for the potential use of Chr and EM in the treatment of human colorectal and cervical carcinomas.

5.
Int J Mol Sci ; 23(21)2022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-36362351

RESUMO

Several human diseases are caused by viruses, including cancer, Type I diabetes, Alzheimer's disease, and hepatocellular carcinoma. In the past, people have suffered greatly from viral diseases such as polio, mumps, measles, dengue fever, SARS, MERS, AIDS, chikungunya fever, encephalitis, and influenza. Recently, COVID-19 has become a pandemic in most parts of the world. Although vaccines are available to fight the infection, their safety and clinical trial data are still questionable. Social distancing, isolation, the use of sanitizer, and personal productive strategies have been implemented to prevent the spread of the virus. Moreover, the search for a potential therapeutic molecule is ongoing. Based on experiences with outbreaks of SARS and MERS, many research studies reveal the potential of medicinal herbs/plants or chemical compounds extracted from them to counteract the effects of these viral diseases. COVID-19's current status includes a decrease in infection rates as a result of large-scale vaccination program implementation by several countries. But it is still very close and needs to boost people's natural immunity in a cost-effective way through phytomedicines because many underdeveloped countries do not have their own vaccination facilities. In this article, phytomedicines as plant parts or plant-derived metabolites that can affect the entry of a virus or its infectiousness inside hosts are described. Finally, it is concluded that the therapeutic potential of medicinal plants must be analyzed and evaluated entirely in the control of COVID-19 in cases of uncontrollable SARS infection.


Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19 , Plantas Medicinais , Viroses , Humanos , COVID-19/epidemiologia , Antivirais/farmacologia , Antivirais/uso terapêutico , Antivirais/química , SARS-CoV-2 , Surtos de Doenças/prevenção & controle , Viroses/tratamento farmacológico , Plantas Medicinais/metabolismo
6.
Curr Pharm Des ; 28(46): 3706-3719, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36278465

RESUMO

BACKGROUND: In late 2019, a highly infectious and pathogenic coronavirus was recognized as Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2), which causes acute respiratory disease, threatening human health and public safety. A total of 448,327,303 documented cases and 6,028,576 deaths have been reported as of March 8th 2022. The COVID-19 vaccines currently undergoing clinical trials or already in use should provide at least some protection against SARS-CoV-2; however, the emergence of new variations as a result of mutations may lessen the effectiveness of the currently available vaccines. Since the efficacy of available drugs and vaccines against COVID-19 is notably lower, there is an urgent need to develop a potential drug to treat this deadly disease. The SARS-CoV-2 spike (SCoV-SG) is the foremost drug target among coronaviruses. OBJECTIVE: The major objectives of the current study are to conduct a molecular docking study investigation of TAT-peptide47-57(GRKKRRQRRRP)-conjugated remodified therapeutics such as ritonavir (RTV), lopinavir (LPV), favipiravir (FPV), remdesivir (RMV), hydroxychloroquine (HCQ), molnupiravir (MNV) and nirmatrelvir (NMV) with (SCoV-SG) structure. METHODS: Molecular docking analysis was performed to study the interaction of repurposed drugs and drugs conjugated with the TAT-peptide with target SARS-CoV-2 spike glycoprotein (PDB ID: 6VYB) using Auto- Dock. Further docking investigation was completed with PatchDock and was visualized by the discovery of the studio visualizer 2020. RESULTS: TAT-peptides are well-characterized immune enhancers that are used in intracellular drug delivery. The results of molecular docking analysis showed higher efficiency and significantly enhanced and improved interactions between TP-conjugated repurposed drugs and the target sites of the SCoV-SG structure. CONCLUSION: The study concluded that TP-conjugated repurposed drugs may be effective in preventing COVID- 19, and therefore, in vitro, in vivo, and clinical trial studies are required in detail.


Assuntos
COVID-19 , Humanos , Antivirais/uso terapêutico , SARS-CoV-2 , Vacinas contra COVID-19 , Preparações Farmacêuticas , Simulação de Acoplamento Molecular , Reposicionamento de Medicamentos , Glicoproteína da Espícula de Coronavírus , Peptídeos , Glicoproteínas
7.
Arab J Chem ; 15(12): 104366, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36276298

RESUMO

We report microwave synthesis of seven unique pyrimidine anchored derivatives (1-7) incorporating multifunctional amino derivatives along with their in vitro anticancer activity and their activity against COVID-19 in silico. 1-7 were characterized by different analytical and spectroscopic techniques. Cytotoxic activity of 1-7 was tested against HCT116 and MCF7 cell lines, whereby 6 exhibited highest anticancer activity on HCT116 and MCF7 with EC50 values of 89.24 ± 1.36 µM and 89.37 ± 1.17 µM, respectively. Molecular docking was performed for derivatives (1-7) on main protease for SARS-CoV-2 (PDB ID: 6LU7). Results revealed that most of the derivatives had superior or equivalent affinity for the 3CLpro, as determined by docking and binding energy scores. 6 topped the rest with highest binding energy score of -8.12 kcal/mol with inhibition constant reported as 1.11 µM. ADME, drug-likeness, and pharmacokinetics properties of 1-7 were tested using Swiss ADME tool. Toxicity analysis was done with pkCSM online server. All derivatives showed high GI absorption. Except 1 and 3, all derivatives showed blood brain barrier permeability. Most derivatives showed negative logKp values suggesting derivatives are less skin permeable and bioavailability score of all derivatives was 0.55. The toxicity analysis demonstrated that all derivatives have no skin sensitization properties. 6 and 7 showed maximum tolerated dose (Human) values of -0.03 and -0.018, respectively and absence of AMES toxicity.

8.
Drug Des Devel Ther ; 16: 1963-1974, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35783198

RESUMO

Introduction: Numerous drugs with potent toxicity against cancer cells are available for treating malignancies, but therapeutic efficacies are limited due to their inefficient tumor targeting and deleterious effects on non-cancerous tissue. Therefore, two improvements are mandatory for improved chemotherapy 1) novel delivery techniques that can target cancer cells to deliver anticancer drugs and 2) methods to specifically enhance drug efficacy within tumors. The loading of inert drug carriers with anticancer agents and peptides which are able to bind (target) tumor-related proteins to enhance tumor drug accumulation and local cytotoxicity is a most promising approach. Objective: To evaluate the anticancer efficacy of Chitosan nanoparticles loaded with human growth hormone hGH fragment 176-191 peptide plus the clinical chemotherapeutic doxorubicin in comparison with Chitosan loaded with doxorubicin alone. Methods: Two sets of in silico experiments were performed using molecular docking simulations to determine the influence of hGH fragment 176-191 peptide on the anticancer efficacy of doxorubicin 1) the binding affinities of hGH fragment 176-191 peptide to the breast cancer receptors, 2) the effects of hGH fragment 176-191 peptide binding on doxorubicin binding to these same receptors. Further, the influence of hGH fragment 176-191 peptide on the anticancer efficacy of doxorubicin was validated using viability assay in Human MCF-7 breast cancer cells. Results: In silico analysis suggested that addition of the hGH fragment to doxorubicin-loaded Chitosan nanoparticles can enhance doxorubicin binding to multiple breast cancer protein targets, while photon correlation spectroscopy revealed that the synthesized dual-loaded Chitosan nanoparticles possess clinically favorable particle size, polydispersity index, as well as zeta potential. Conclusion: These dual-loaded Chitosan nanoparticles demonstrated greater anti-proliferative activity against a breast cancer cell line (MCF-7) than doxorubicin-loaded Chitosan. This dual-loading strategy may enhance the anticancer potency of doxorubicin and reduce the clinical side effects associated with non-target tissue exposure.


Assuntos
Antineoplásicos , Neoplasias da Mama , Quitosana , Hormônio do Crescimento Humano , Nanopartículas , Antineoplásicos/química , Neoplasias da Mama/tratamento farmacológico , Quitosana/química , Quitosana/farmacologia , Doxorrubicina , Feminino , Humanos , Células MCF-7 , Simulação de Acoplamento Molecular , Nanopartículas/química , Peptídeos/uso terapêutico
9.
Biomed Pharmacother ; 150: 112985, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35658219

RESUMO

Diabetes is a complicated multifactorial disorder in which the patient generally observes polyphagia, polydipsia, and polyuria due to uncontrolled growth in blood sugar levels. For its management, the pharmaceutical industry is working day and night to find a better drug with no or least toxicity. That's why nowadays a more focused branch is to use herbal phytoconstituents for its prevention. Shikonin is a naphthoquinone natural dye that is isolated from the plants of the Boraginaceae family and has proven its role as an anti-cancer, anti-inflammatory, and anti-gonadotrophic agent. In our previous study, we have published its anti-diabetic action by inhibiting the enzyme protein tyrosine phosphatase 1B. In this study, we were more focused on finding out the role of Shikonin and its pharmacophores by inhibiting the action of aldose reductase (AR) enzyme. The study was conducted using pharmacophore modeling, molecular docking, and molecular dynamics simulation studies. The absorption, distribution, metabolism, excretion (ADME), and toxicity profile were also evaluated in this study. Along with all the computational biology parameters we also focused on the in vitro activity and kinetic study of inhibitory activity of Shikonin against aldose reductase.


Assuntos
Diabetes Mellitus , Naftoquinonas , Aldeído Redutase/metabolismo , Diabetes Mellitus/tratamento farmacológico , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Simulação de Acoplamento Molecular , Naftoquinonas/farmacologia , Naftoquinonas/uso terapêutico
10.
Molecules ; 27(3)2022 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-35164000

RESUMO

Gastric cancer is the fifth most frequent cancer and the third major cause of mortality worldwide. Helicobacter pylori, a bacterial infection linked with GC, injects the cytotoxin-associated antigen A (CagA; an oncoprotein) into host cells. When the phosphorylated CagA protein enters the cell, it attaches to other cellular components, interfering with normal cellular signaling pathways. CagA plays an important role in the progression of GC by interacting with phosphatidylserine of the host cell membrane. Therefore, disrupting the CagA-phosphatidylserine connection using small molecules appears to be a promising therapeutic approach. In this report, we screened the natural compounds from ZINC database against the CagA protein using the bioinformatics tools. Hits were initially chosen based on their physicochemical, absorption, distribution, metabolism, excretion, and toxicity (ADMET) characteristics, as well as other drug-like characteristics. To locate safe and effective hits, the PAINS filter, binding affinities estimation, and interaction analysis were used. Three compounds with high binding affinity and specificity for the CagA binding pocket were discovered. The final hits, ZINC153731, ZINC69482055, and ZINC164387, were found to bind strongly with CagA protein, with binding energies of -11.53, -10.67, and -9.21 kcal/mol, respectively, which were higher than that of the control compound (-7.25 kcal/mol). Further, based on binding affinity and interaction pattern, two leads (ZINC153731, ZINC69482055) were chosen for molecular dynamics (MD) simulation analysis. MD results showed that they displayed stability in their vicinity at 100 ns. This study suggested that these compounds could be used as possible inhibitors of CagA protein in the fight against GC. However, additional benchwork tests are required to validate them as CagA protein inhibitors.


Assuntos
Proteínas de Bactérias/antagonistas & inibidores , Produtos Biológicos/farmacologia , Simulação por Computador , Infecções por Helicobacter/complicações , Helicobacter pylori/isolamento & purificação , Neoplasias Gástricas/tratamento farmacológico , Antígenos de Bactérias , Infecções por Helicobacter/microbiologia , Ensaios de Triagem em Larga Escala , Humanos , Simulação de Dinâmica Molecular , Estrutura Molecular , Neoplasias Gástricas/microbiologia
11.
J Pathol Inform ; 13: 100154, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36605108

RESUMO

Context: Analysis of diagnostic information in pathology reports for the purposes of clinical or translational research and quality assessment/control often requires manual data extraction, which can be laborious, time-consuming, and subject to mistakes. Objective: We sought to develop, employ, and evaluate a simple, dictionary- and rule-based natural language processing (NLP) algorithm for generating searchable information on various types of parameters from diverse surgical pathology reports. Design: Data were exported from the pathology laboratory information system (LIS) into extensible markup language (XML) documents, which were parsed by NLP-based Python code into desired data points and delivered to Excel spreadsheets. Accuracy and efficiency were compared to a manual data extraction method with concordance measured by Cohen's κ coefficient and corresponding P values. Results: The automated method was highly concordant (90%-100%, P<.001) with excellent inter-observer reliability (Cohen's κ: 0.86-1.0) compared to the manual method in 3 clinicopathological research scenarios, including squamous dysplasia presence and grade in anal biopsies, epithelial dysplasia grade and location in colonoscopic surveillance biopsies, and adenocarcinoma grade and amount in prostate core biopsies. Significantly, the automated method was 24-39 times faster and inherently contained links for each diagnosis to additional variables such as patient age, location, etc., which would require additional manual processing time. Conclusions: A simple, flexible, and scaleable NLP-based platform can be used to correctly, safely, and quickly extract and deliver linked data from pathology reports into searchable spreadsheets for clinical and research purposes.

12.
Environ Sci Pollut Res Int ; 29(41): 61972-61992, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34382170

RESUMO

The free radicals produced by cigarette smoking are responsible for tissue damage, heart and lung diseases, and carcinogenesis. The effect of tobacco on the central nervous system (CNS) has received increased attention nowadays in research. Therefore, to explore the molecular interaction of cigarette smoke carcinogens (CSC) 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanol (NNAL), 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone (NNK), and N'-nitrosonornicotine (NNN) with well-known targets of CNS-related disorders, acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE) enzymes, a cascade of the computational study was conducted including molecular docking and molecular dynamics simulations (MDS). The investigated results of NNAL+AChEcomplex, NNK+AChEcomplex, and NNK+BuChEcomplex based on intermolecular energies (∆G) were found to -8.57 kcal/mol, -8.21 kcal/mol, and -8.08 kcal/mol, respectively. MDS deviation and fluctuation plots of the NNAL and NNK interaction with AChE and BuChE have shown significant results. Further, Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) results shown the best total binding energy (Binding∆G) -87.381 (+/-13.119) kJ/mol during NNK interaction with AChE. Our study suggests that CSC is well capable of altering the normal biomolecular mechanism of CNS; thus, obtained data could be useful to design extensive wet laboratory experimentation to know the effects of CSC on human CNS.


Assuntos
Fumar Cigarros , Nitrosaminas , Acetilcolinesterase , Butirilcolinesterase , Carcinógenos/metabolismo , Sistema Nervoso Central/metabolismo , Humanos , Simulação de Acoplamento Molecular , Nitrosaminas/química , Nicotiana/metabolismo
13.
Molecules ; 26(13)2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34208908

RESUMO

Diabetes mellitus is a multifactorial disease that affects both developing and developed countries and is a major public health concern. Many synthetic drugs are available in the market, which counteracts the associated pathologies. However, due to the propensity of side effects, there is an unmet need for the investigation of safe and effective drugs. This research aims to find a novel phytoconstituent having diminished action on blood glucose levels with the least side effects. Shikonin is a naturally occurring naphthoquinone dying pigment obtained by the roots of the Boraginaceae family. Besides its use as pigments, it can be used as an antimicrobial, anti-inflammatory, and anti-tumor agent. This research aimed to hypothesize the physicochemical and phytochemical properties of Shikonin's in silico interaction with protein tyrosine phosphate 1B, as well as it's in vitro studies, in order to determine its potential anti-diabetic impact. To do so, molecular docking experiments with target proteins were conducted to assess their anti-diabetic ability. Analyzing associations with corresponding amino acids revealed the significant molecular interactions between Shikonin and diabetes-related target proteins. In silico pharmacokinetics and toxicity profile of Shikonin using ADMET Descriptor, Toxicity Prediction, and Calculate Molecular Properties tools from Biovia Discovery Studio v4.5. Filter by Lipinski and Veber Rule's module from Biovia Discovery Studio v4.5 was applied to assess the drug-likeness of Shikonin. The in vitro studies exposed that Shikonin shows an inhibitory potential against the PTP1B with an IC50 value of 15.51 µM. The kinetics studies revealed that it has a competitive inhibitory effect (Ki = 7.5 M) on the enzyme system, which could be useful in the production of preventive and therapeutic agents. The findings of this research suggested that the Shikonin could be used as an anti-diabetic agent and can be used as a novel source for drug delivery.


Assuntos
Inibidores Enzimáticos/química , Hipoglicemiantes/química , Simulação de Acoplamento Molecular , Naftoquinonas/química , Proteína Tirosina Fosfatase não Receptora Tipo 1 , Regulação Alostérica , Humanos , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Proteína Tirosina Fosfatase não Receptora Tipo 1/química , Relação Estrutura-Atividade
14.
Front Chem ; 9: 630357, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33777897

RESUMO

A molecular modeling assisted rational design and synthesis of naphthalene diimide linked bis-naphthalimides as potential DNA interactive agents is described. Chemical templates incorporating naphthalene diimide as a linker in bis-naphthalimide motif were subjected to molecular docking analysis at specific intercalation and telomeric DNA G-quadruplex sites. Excellent results were obtained, which were better than the standards. A short and convenient synthetic route was employed to access these hybrids experimentally, followed by evaluation of their ability to cause thermal denaturation of DNA and cytotoxic properties along with ADME predictions. The obtained results provided useful insights and two potential molecules were identified for further development.

15.
Front Chem ; 9: 808556, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35155379

RESUMO

An efficient atom-economical synthetic protocol to access new imidazole-based N-phenylbenzamide derivatives is described. A one-pot three-component reaction was utilized to provide a series of N-phenylbenzamide derivatives in a short reaction time (2-4 h) with an 80-85% yield. The cytotoxic evaluation revealed that derivatives 4e and 4f exhibited good activity, with IC50 values between 7.5 and 11.1 µM against the tested cancer cell lines. Computational studies revealed interesting insights: the docking of the active derivatives (4e and 4f) showed a higher affinity toward the target receptor protein than the control. Molecular dynamic simulations revealed that the active derivatives form stable complexes with the ABL1 kinase protein. Moreover, the ADME and drug-likeness of the derivatives reinforced the potential of the derivatives to be taken up for further development as anticancer agents.

16.
Semin Cancer Biol ; 69: 109-128, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-31891780

RESUMO

Breast cancer is one of the most prevalent and reoccurring cancers and the second most common reason of death in women. Despite advancements in therapeutic strategies for breast cancer, early tumor recurrence and metastasis in patients indicate resistance to chemotherapeutic medicines, such as paclitaxel due to the abnormal expression of ER and EGF2 in breast cancer cells. Therefore, the development of alternatives to paclitaxel is urgently needed to overcome challenges involving drug resistance. An increasing number of studies has revealed miRNAs as novel natural alternative substances that play a crucial role in regulating several physiological processes and have a close, adverse association with several diseases, including breast cancer. Due to the therapeutic potential of miRNA and paclitaxel in cancer research, the current review focuses on the differential roles of various miRNAs in breast cancer development and treatment. miRNA delivery to a specific target site, the development of paclitaxel and miRNA formulations, and nanotechnological strategies for the delivery of nanopaclitaxel in the management of breast cancer are discussed. These strategies involve improving the cellular uptake and bioavailability and reducing the toxicity of free paclitaxel to achieve accumulation tumor site. Furthermore, a molecular docking study was performed to ascertain the enhanced anticancer activity of the nanoformulation of ANG1005 and Abraxane. An in silico analysis revealed that ANG1005 and Abraxane nanoformulations have superior and significantly enhanced interactions with the proteins α-tubulin and Bcl-2. Therefore, ANG1005 and Abraxane may be more suitable in the therapeutic management of breast cancer than the existing free paclitaxel. miRNAs can revert abnormal gene expression to normalcy; since miRNAs serve as tumor suppressors. Therefore, restoration of particular miRNAs levels as a replacement therapy may be an effective endocrine potential strategy for treating ER positive/ negative breast cancers.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Sistemas de Liberação de Medicamentos , MicroRNAs/genética , Nanopartículas/administração & dosagem , Nanotecnologia/métodos , Paclitaxel/análogos & derivados , Peptídeos/administração & dosagem , Receptores de Estrogênio/metabolismo , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/química , Neoplasias da Mama/patologia , Simulação por Computador , Gerenciamento Clínico , Resistencia a Medicamentos Antineoplásicos , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Simulação de Acoplamento Molecular , Nanopartículas/química , Paclitaxel/administração & dosagem , Paclitaxel/química , Peptídeos/química
17.
Semin Cancer Biol ; 69: 100-108, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-31562954

RESUMO

Neuroblastoma (NB) is a widely diagnosed cancer in children, characterized by amplification of the gene encoding the MYCN transcription factor, which is highly predictive of poor clinical outcome and metastatic disease. microRNAs (a class of small non-coding RNAs) are regulated by MYCN transcription factor in neuroblastoma cells. The current research is focussed on identifying differential role of miRNAs and their interactions with signalling proteins, which are intricately linked with cellular processes like apoptosis, proliferation or metastasis. However, the therapeutic success of miRNAs is limited by pharmaco-technical issues which are well counteracted by nanotechnological advancements. The nanoformulated miRNAs unload anti-cancer drugs in a controlled and prespecified manner at target sites, to influence the activity of target protein in amelioration of NB. Recent advances and developments in the field of miRNAs-based systems for clinical management of NBs and the role of nanotechnology to overcome challenges with drug delivery of miRNAs have been reviewed in this paper.


Assuntos
Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , MicroRNAs/administração & dosagem , Nanopartículas/administração & dosagem , Nanotecnologia/métodos , Neuroblastoma/tratamento farmacológico , Animais , Gerenciamento Clínico , Humanos , MicroRNAs/genética , Nanopartículas/química , Neuroblastoma/genética , Neuroblastoma/patologia
18.
Asian Pac J Cancer Prev ; 21(5): 1349-1355, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32458643

RESUMO

BACKGROUND AND OBJECTIVE: Topoisomerase TOP-IIA (TTOP-IIA) is widely used as a significant target for cancer therapeutics because of its involvement in cell proliferation. Steroidal drugs have been suggested for breast cancer treatment as aromatase enzymes inhibitors . TTOP-IIA inhibitors can be used as a target for the development of new cancer therapeutics. MATERIALS AND METHODS: In this study, we conducted a docking study on steroidal drugs Anastrozole (ANA), Letrozole (LET), and exemestane (EXE) with TTOP-IIA  to explore the therapeutic area of these drugs. RESULTS: The binding interaction of EXE drug had significant docking interaction which is followed by ANA and LET. Thus, all these drugs could be used to inhibit the TTOP-IIA mediated cell proliferation and could be a hope to treat the other types of cancers. Among all three tested steroidal drugs, EXE showed binding energy -7.05 kcal/mol, hydrogen bond length1.78289 Å and amino acid involved in an interaction was A: LYS723:HZ3 -: UNK1:O6. CONCLUSION: The obtained data showed the most significant binding interaction analyzed with the tested enzyme. Thus, in vitro laboratory experimentation and in vivo research are necessary to put forward therapeutic repositioning of these drugs to establish them as a broad spectrum potential anticancer drugs.
.


Assuntos
Antineoplásicos/química , Antineoplásicos/metabolismo , Inibidores da Aromatase/química , Inibidores da Aromatase/metabolismo , Neoplasias da Mama/tratamento farmacológico , DNA Topoisomerases Tipo II/química , DNA Topoisomerases Tipo II/metabolismo , Anastrozol/química , Anastrozol/metabolismo , Androstadienos/química , Androstadienos/metabolismo , Neoplasias da Mama/enzimologia , Neoplasias da Mama/patologia , Simulação por Computador , Feminino , Humanos , Letrozol/química , Letrozol/metabolismo , Conformação Proteica
19.
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
20.
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
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