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1.
J Mol Struct ; 1272: 134160, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36128074

RESUMO

The CD147 / Cyp A interaction is a critical pathway in cancer types and an essential factor in entering the COVID-19 virus into the host cell. Melittin acts as an inhibitory peptide in cancer types by blocking the CD147/ Cyp A interaction. The clinical application of Melittin is limited due to weak penetration into cancer cells. TAT is an arginine-rich peptide with high penetration ability into cells widely used in drug delivery systems. This study aimed to design a hybrid peptide derived from Melittin and TAT to inhibit CD147 /Cyp A interaction. An amino acid region with high anti-cancer activity in Melittin was selected based on the physicochemical properties. Based on the results, a truncated Melittin peptide with 15 amino acids by the GGGS linker was fused to a TAT peptide (nine amino acids) to increase the penetration rate into the cell. A new hybrid peptide analog(TM) was selected by replacing the glycine with serine based on random point mutation. Docking results indicated that the TM peptide acts as an inhibitory peptide with high binding energy when interacting with CD147 and the CypA proteins. RMSD and RMSF results confirmed the high stability of the TM peptide in interaction with CD147. Also, the coarse-grained simulation showed the penetration potential of TM peptide into the DOPS-DOPC model membrane. Our findings indicated that the designed multifunctional peptide could be an attractive therapeutic candidate to halter tumor types and COVID-19 infection.

2.
Braz. j. biol ; 83: e244479, 2023. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1285635

RESUMO

Abstract The objective of the present study was to analyse the bioactive compounds of the leaves of Conocarpus lancifolius (C. lancifolius). The GC-MS analysis of the hot methanolic extract of the leaves (HMEL) of C. lancifolius exhibited the bioactive compounds such as 1-(3-Methoxy-2-nitrobenzyl) iso quinoline, morphin-4-ol-6,7-dione, 1-bromo-N-methyl-, phytol, hexadecanoic acid, 2,3-dihydroxypropyl ester, 2,2':4',2"-terthiophene, ethyl iso-allocholate, caryophyllene oxide, campesterol, epiglobulol, cholestan-3-ol, 2-methylene-, (3á,5à)-, dasycarpidan-1-methanol, acetate (ester) and oleic acid, eicosyl ester. The FT-IR analysis of HMEL of C. lancifolius showed a unique peak at 3184, 2413, 1657 cm-1 representing coumaric acid, chlorogenic acid and ferulic acid. The HMEL of C. lancifolius was actively inhibiting the proliferation of breast cancer cells MCF-7 ATCC at the concentration of 72.66 ± 8.21 µg/ml as IC50 value. The HMEL of C. lancifolius also revealed a good spectrum of activity against Gram-positive and Gram-negative bacterial cultures screened in this work. The activity observed has shown more or less similar effects against screened bacteria. However, the magnitude of potentiality was significantly lesser compared to standard ciprofloxacin disc at p< 0.001 level (99% confidence intervals). Furthermore, the study demonstrating the bioactive compounds can be isolated from the leaves of C. lancifolius.


Resumo O objetivo do presente estudo foi analisar os compostos bioativos das folhas de Conocarpus lancifolius (C. lancifolius). A análise por GC-MS do extrato metanólico quente das folhas (HMEL) de C. lancifolius exibiu os compostos bioativos como 1- (3-Metoxi-2-nitrobenzil) isoquinolina, morfina-4-ol-6,7- diona, 1-bromo-N-metil-, fitol, ácido hexadecanoico, 2,3-di-hidroxipropil éster, 2,2 ': 4', 2 " - tertiofeno, isoalocolato de etil, óxido de cariofileno, campesterol, epiglobulol, colestano -3-ol, 2-metileno-, (3á, 5à) -, dasycarpidan-1-metanol, acetato (éster) e ácido oleico, éster eicosílico. A análise FT-IR de HMEL de C. lancifolius mostrou um pico único em 3184, 2413, 1657 cm-1 representando ácido cumarico, ácido clorogênico e ácido ferúlico. O HMEL de C. lancifolius inibiu ativamente a proliferação de células de câncer de mama MCF-7 ATCC na concentração de 72,66 ± 8,21 µg / ml como valor de IC50. O HMEL de C. lancifolius também revelou bom espectro de atividade contra culturas de bactérias Gram-positivas e Gram-negativas rastreadas neste trabalho. A atividade observada mostrou efeitos mais ou menos semelhantes contra bactérias rastreadas. No entanto, a magnitude da potencialidade foi significativamente menor em comparação com o disco de ciprofloxacina padrão em nível de p < 0,001 (intervalos de confiança de 99%). Além disso, o estudo demonstrando os compostos bioativos pode ser isolado das folhas de C. lancifolius.


Assuntos
Árvores , Folhas de Planta , Arábia Saudita , Extratos Vegetais/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier , Antibacterianos/farmacologia
3.
Mol Divers ; 2022 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-36114912

RESUMO

A library of benzimidazole briged pyrazolo[1,5-a]pyrimidine (6a-q) was designed, synthesized and subjected for evaluation for cytotoxic potential. Antiproliferative activity, ranging from 3.1-51.5 µM, was observed against a panel of cancer cell lines which included MCF-7 (breast cancer), A549 (lung cancer), HeLa (cervical cancer) and SiHa (cervical cancer). Among them, 6k, 6l, 6n and 6o have shown significant cytotoxicity and were investigated further to study their probable mechanism of action against MCF-7 cell line. Accumulation of cells at sub-G1 phase was observed in flow cytometric analysis. The detachment of cells from substratum and membrane blebbing seen under bright field microscopy supports the ability of these conjugates to induce apoptosis. Immunostaining and western blot analysis showed EGFR, p-EGFR, STAT3, and p-STAT3 significant downregulation. Western blot analysis demonstrated an elevated level of apoptotic proteins such as p53, p21, Bax, whereas a decrease in the antiapoptotic protein Bcl-2 and procaspase-9, confirming the ability of these conjugates to trigger cell death by apoptosis. EGFR kinase assay confirms the specific activity of conjugates. Molecular docking simulation study disclosed that these molecules fit well in ATP-binding pocket of EGFR. The analysis of docking poses and the atomic interactions of different conjugates rationalize the structural-activity relationship in this series. Benzimidazole-linked pyrazolo[1,5-a]pyrimidine conjugates were synthesized and evaluated for their anticancer potential. All the conjugates have significant anticancer potential. Further mechanistic studies revealed that these conjugates arrest cancer cell growth by EGFR/STAT3 inhibition.

4.
BMC Chem ; 16(1): 68, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36109764

RESUMO

BACKGROUND: A novel series of thiazolidine-2,4-dione molecules was derived and their chemical structures were established using physiochemical parameters and spectral techniques (1H-NMR, IR, MS etc.). The synthesized molecule were then evaluated for their antioxidant, anticancer and antimicrobial potential. RESULTS AND DISCUSSION: Serial tube dilution method was employed to evaluate the antimicrobial potential against selected fungal and bacterial strains by taking fluconazole and cefadroxil as reference antifungal and antibacterial drugs respectively. 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity was used to assess the antioxidant potential of the synthesized analogues. Further, the anticancer potential of the selected molecules was assessed against DU-145 cancer cell lines using MTT assay. The drug-likeness was also evaluated by studying in-silico ADME parameters of the synthesized analogues. CONCLUSION: In antioxidant evaluation studies, the analogue H5 with IC50 = 14.85 µg/mL was found to be the most active molecule. The antimicrobial evaluation outcomes suggested that the molecules H5, H13, H15 and H18 possessed moderate to promising activity against the selected species of microbial strains having MIC range 7.3 µM to 26.3 µM. The results of anticancer evaluation revealed that all the screened derivatives possess mild anticancer potential. The in-silico ADME studies revealed that all the compounds were found to be drug-like.

5.
Nutrients ; 14(17)2022 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-36079792

RESUMO

Date palm fruit seed (Phoenix dactylifera L.) extract (DSE), an under-utilized resource, is a rich source of polyphenols with high potency for disease prevention and antioxidative activities. For the first time, the present study demonstrated that DSE inhibits labile iron activity and DNA and BSA damage and inhibits acetylcholinesterase and tyrosinase activities. Moreover, DSE reduces the proliferation of hepatic, colorectal, and breast cancer cells dose-dependently through apoptotic mechanisms. Furthermore, DSE significantly suppressed the expression of both BCl-2 and P21 genes and increased the P53 expression level when compared with the untreated cells and the 5-FU treated cells. These findings suggest a strong potential for DSE in protecting against the iron-catalyzed ferroptosis that results in programmed cell death. The results also confirm the efficacy of DSE against cancer cells. Therefore, DSE constitutes a valuable candidate for developing functional foods and for natural compound-based chemotherapy for the pharmaceutical and nutraceutical industries.


Assuntos
Dano ao DNA/efeitos dos fármacos , Ferro/metabolismo , Neoplasias/tratamento farmacológico , Phoeniceae , Extratos Vegetais/farmacologia , Sementes/química , Acetilcolinesterase/metabolismo , DNA/metabolismo , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Frutas/química , Neoplasias/metabolismo , Neoplasias/patologia , Neoplasias/prevenção & controle , Extratos Vegetais/metabolismo , Polifenóis/metabolismo , Polifenóis/farmacologia
6.
Int J Oncol ; 61(4)2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36082810

RESUMO

Most proteins maintain protein homeostasis via post­translational modifications, including the ubiquitin­proteasome system. Deubiquitinating enzymes (DUBs) have essential intercellular roles, such as responses to DNA damage, proteolysis and apoptosis. Therefore, it is important to understand DUB­related diseases to identify DUBs that target abnormally regulated proteins in cells. Ovarian tumor deubiquitinase 6A (OTUD6A) was previously reported as a downregulated DUB in HCT116 cells with p53 knockdown. Therefore, it was expected that the relationship between OTUD6A and p53 would affect cell proliferation. In the present study, putative substrates of OTUD6A related to the p53 signaling pathway were identified. Application of liquid chromatography­tandem mass spectrometry and proteomic analysis led to the identification of nucleolin (known to bind p53) as a binding protein. In addition, immunoprecipitation studies determined that caspase­7, an apoptotic protein, is associated with p53 signaling and is regulated by OTUD6A. It was further identified that OTUD6A regulates the protein stability of nucleolin, but not caspase­7. It was also demonstrated that OTUD6A acts as a respective DUB through the deubiquitination of K48­linked polyubiquitin chain of nucleolin and the K63­linked polyubiquitin chain of caspase­7. Furthermore, overexpression of OTUD6A induced cell proliferation via enhancing cell cycle progression of MCF7 cells. Taken together, OTUD6A may be proposed as a target for anticancer therapy.


Assuntos
Enzimas Desubiquitinantes , Neoplasias Ovarianas , Poliubiquitina , Caspase 7/metabolismo , Proliferação de Células , Enzimas Desubiquitinantes/genética , Enzimas Desubiquitinantes/metabolismo , Feminino , Humanos , Neoplasias Ovarianas/genética , Fosfoproteínas/metabolismo , Poliubiquitina/genética , Poliubiquitina/metabolismo , Proteômica , Proteínas de Ligação a RNA/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Ubiquitinação
7.
Oncoimmunology ; 11(1): 2116844, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36046811

RESUMO

IRE1α is one of the three ER transmembrane transducers of the Unfolded Protein Response (UPR) activated under endoplasmic reticulum (ER) stress. IRE1α activation has a dual role in cancer as it may be either pro- or anti-tumoral depending on the studied models. Here, we describe the discovery that exogenous expression of IRE1α, resulting in IRE1α auto-activation, did not affect cancer cell proliferation in vitro but resulted in a tumor-suppressive phenotype in syngeneic immunocompetent mice. We found that exogenous expression of IRE1α in murine colorectal and Lewis lung carcinoma cells impaired tumor growth when syngeneic tumor cells were subcutaneously implanted in immunocompetent mice but not in immunodeficient mice. Mechanistically, the in vivo tumor-suppressive effect of overexpressing IRE1α in tumor cells was associated with IRE1α RNAse activity driving both XBP1 mRNA splicing and regulated IRE1-dependent decay of RNA (RIDD). We showed that the tumor-suppressive phenotype upon IRE1α overexpression was characterized by the induction of apoptosis in tumor cells along with an enhanced adaptive anti-cancer immunosurveillance. Hence, our work indicates that IRE1α overexpression and/or activation in tumor cells can limit tumor growth in immunocompetent mice. This finding might point toward the need of adjusting the use of IRE1α inhibitors in cancer treatments based on the predominant outcome of the RNAse activity of IRE1α.


Assuntos
Endorribonucleases , Neoplasias , Animais , Endorribonucleases/genética , Endorribonucleases/metabolismo , Imunidade , Camundongos , Processos Neoplásicos , Proteínas Serina-Treonina Quinases/genética , Transdução de Sinais , Proteína 1 de Ligação a X-Box/genética , Proteína 1 de Ligação a X-Box/metabolismo
8.
Med Oncol ; 39(11): 179, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36048256

RESUMO

The DEAD-box helicase family member DDX3 is involved in many diseases, such as viral infection, inflammation, and cancer. Many studies in the last decade have revealed the role of DDX3 in tumorigenesis and metastasis. DDX3 has both tumour suppressor and oncogenic effect, in the present study we have evaluated the expression levels of DDX3 in cervical squamous cell carcinoma at mRNA level via real-time PCR and protein level via Immunohistochemistry. DDX3 has become a molecule of interest in cancer biology that promotes drug resistance by adaptive response inevitably leading to treatment failure. One approach to avoid the development of resistant to disease is to create novel drugs that target the overexpressed proteins, we designed and synthesized a novel 7-azaindole derivative (7-AID) compound, {5-[1H-pyrrolo (2, 3-b) pyridin-5-yl] pyridin-2-ol]} that could lodge within the adenosine-binding pocket of the DDX3 (PDB ID: 2I4I). The binding efficacy of 7-AID compound with DDX3 was analysed by molecular docking studies. 7-AID was found to interact with the key residues Tyr200 and Arg202 from the Q-motif rendered by π-interactions and hydrogen bonds within the binding pocket with good docking score - 7.99 kcal/mol. The cytotoxicity effect of 7-AID compound was evaluated using MTT assay on human cervical carcinoma cells (HeLa) and breast cancer cells (MCF-7 and MDA MB-231) and the compound shown effective inhibitory concentration (IC50) on Hela cells 16.96 µM/ml and 14.12 and 12.69 µM/ml on MCF-7 and MDA MB-231, respectively. Further, the in-vitro, in-vivo anti-cancer and anti-angiogenic assessment of 7-AID compound was evaluated on Hela cells using scratch wound-healing assay, DAPI staining, cell cycle analysis, immunoblotting, and chorioallontoic membrane assay. Furthermore, the inhibitory effect of derivative compound on DDX3 was investigated in HeLa, MCF-7, and MDA MB-231 cells at the mRNA and protein levels. The results showed that the 7-AID compound effectively inhibited DDX3 in a dose-dependent manner, and the findings suggest that the compound could be used as a potential DDX3 inhibitor.


Assuntos
RNA Helicases DEAD-box , Linhagem Celular Tumoral , Proliferação de Células , RNA Helicases DEAD-box/metabolismo , Células HeLa , Humanos , Indóis , Simulação de Acoplamento Molecular , RNA Mensageiro
9.
World J Gastroenterol ; 28(33): 4787-4811, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36156922

RESUMO

BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality. Cancer stem cells (CSCs) in CRC, which are spared by many chemotherapeutics, have tumorigenic capacity and are believed to be the reason behind cancer relapse. So far, there have been no effective drugs to target colon CSCs. Diiminoquinone (DIQ) has shown promising effects on targeting colon cancer. However, there is limited research on the effects of DIQ on eradicating CSCs in CRC. AIM: To investigate the anticancer potential of DIQ on colon CSCs in two-dimensional (2D) and three-dimensional (3D) models using colonospheres and patient-derived organoids. METHODS: Various 2D methods have been used to assess the effect and the mechanism of DIQ on HCT116 and HT29 cell lines including cell proliferation and viability assays, migration and invasion assays, immunofluorescence staining, and flow cytometry. The potency of DIQ was also assessed in 3D culture using the sphere formation assay and colon cancer patient-derived organoid model. RESULTS: Our results showed that DIQ significantly inhibited cell proliferation, migration, and invasion in HCT116 and HT29 cell lines. DIQ treatment induced apoptosis along with an accumulation of HCT116 and HT29 cancer cells in the sub-G1 region and an increase in reactive oxygen species in both CRC cell lines. DIQ reduced sphere-forming and self-renewal ability of colon cancer HCT116 and HT29 stem/progenitor cells at sub-toxic doses of 1 µmol/L. Mechanistically, DIQ targets CSCs by downregulating the main components of stem cell-related -catenin, AKT, and ERK oncogenic signaling pathways. Potently, DIQ displayed a highly significant decrease in both the count and the size of the organoids derived from colon cancer patients as compared to control and 5-fluorouracil conditions. CONCLUSION: This study is the first documentation of the molecular mechanism of the novel anticancer therapeutic DIQ via targeting CSC, a promising compound that needs further investigation.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Cateninas/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Fluoruracila/farmacologia , Células HCT116 , Células HT29 , Humanos , Recidiva Local de Neoplasia , Células-Tronco Neoplásicas/metabolismo , Proteínas Proto-Oncogênicas c-akt , Espécies Reativas de Oxigênio
10.
Int J Mol Sci ; 23(18)2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36142616

RESUMO

Green tea's (Camellia sinensis) anticancer and anti-inflammatory effects are well-known. Catechins are the most effective antioxidants among the physiologically active compounds found in Camellia sinesis. Recent research demonstrates that the number of hydroxyl groups and the presence of specific structural groups have a substantial impact on the antioxidant activity of catechins. Unfermented green tea is the finest source of these chemicals. Catechins have the ability to effectively neutralize reactive oxygen species. The catechin derivatives of green tea include epicatechin (EC), epigallocatechin (EGC), epicatechin gallate (ECG) and epigallocatechin gallate (EGCG). EGCG has the greatest anti-inflammatory and anticancer potential. Notably, catechins in green tea have been explored for their ability to prevent a variety of cancers. Literature evidence, based on epidemiological and laboratory studies, indicates that green tea catechins have certain properties that can serve as the basis for their consideration as lead molecules in the synthesis of novel anticancer drugs and for further exploration of their role as pharmacologically active natural adjuvants to standard chemotherapeutics. The various sections of the article will focus on how catechins affect the survival, proliferation, invasion, angiogenesis, and metastasis of tumors by modulating cellular pathways.


Assuntos
Catequina , Neoplasias , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Catequina/farmacologia , Catequina/uso terapêutico , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/prevenção & controle , Espécies Reativas de Oxigênio , Chá/química
11.
Int J Mol Sci ; 23(18)2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36142713

RESUMO

In the present study, an amphiphilic polymer was prepared by conjugating methoxy poly(ethylene glycol) (mPEG) with tetraphenylethene (TPE) via disulfide bonds (Bi(mPEG-S-S)-TPE). The polymer could self-assemble into micelles and solubilize hydrophobic anticancer drugs such as paclitaxel (PTX) in the core. Combining the effect of TPE, mPEG, and disulfide bonds, the Bi(mPEG-S-S)-TPE micelles exhibited excellent AIE feature, reduced protein adsorption, and redox-sensitive drug release behavior. An in vitro intracellular uptake study demonstrated the great imaging ability and efficient internalization of Bi(mPEG-S-S)-TPE micelles. The excellent anticancer effect and low systemic toxicity were further evidenced by the in vivo anticancer experiment. The Bi(mPEG-S-S)-TPE micelles were promising drug carriers for chemotherapy and bioimaging.


Assuntos
Antineoplásicos , Micelas , Antineoplásicos/química , Antineoplásicos/farmacologia , Dissulfetos/farmacologia , Portadores de Fármacos/farmacologia , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Oxirredução , Paclitaxel/química , Paclitaxel/farmacologia , Polietilenoglicóis/química , Polímeros/química
12.
Clin Lymphoma Myeloma Leuk ; 22 Suppl 2: S345, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36164025

RESUMO

CONTEXT: Hodgkin lymphoma (HL) represents two-thirds of all lymphomas diagnosed in Lebanon. Due to the COVID-19 pandemic and the unprecedented financial crisis, shortages of oncology drugs are now common in Lebanon. The shortage of conventional agents has created remarkable challenges for both HL patients and health care providers. We lack studies that document the outcome of HL in Lebanon during this period. OBJECTIVE: To determine the outcome of HL patients treated in Lebanon during the period of drug shortages. DESIGN, SETTING, AND PARTICIPANTS: This retrospective study included 52 HL patients diagnosed between October 2019 and December 2021 at Hôtel Dieu de France Hospital in Lebanon. Patients had classical or nodular lymphocyte-predominant subtypes. MAIN OUTCOME MEASURES: The treatment patterns, frequency of incomplete protocols, missing agents, and response to first-line treatment were analyzed. RESULTS: A total of 52 patients were reviewed with a median age of 35 years (range, 15-85 years); 52% were male. In this study, 65% of patients had B symptoms at diagnosis, 70% had no comorbidities, 64% had an advanced stage, 60% had bulky disease, and 90% had low- to intermediate-risk disease according to the International Prognostic Score. The nodular sclerosing subtype was the most common histological subtype (77%). The ABVD regimen was offered to 85% of patients and radiotherapy was offered to 10%. Eleven patients (22%) did not receive the full treatment per protocol due to drug shortage: 8 patients (15%), 2 patients (4%), and 1 patient (2%) had missing bleomycin, dacarbazine, and vinblastine, respectively. Of these patients, 6 (54%) received treatment without the missing agent, 4 (36%) imported the medication from an external source at their own expense, and 1 (9%) was switched to another protocol. Among 11 patients who did not receive proper therapy, the rates of complete response, partial response, stable disease, and progressive disease were 70%, 15%, 5%, and 10%, respectively. CONCLUSIONS: In this single-institution study from Lebanon, the outcomes of patients with HL treated during an unprecedented crisis and drugs shortage were comparable to those of previous reports. This emphasizes the resilience of the Lebanese population and adaptability despite hard conditions.


Assuntos
COVID-19 , Doença de Hodgkin , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/uso terapêutico , COVID-19/tratamento farmacológico , COVID-19/epidemiologia , Dacarbazina/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Doença de Hodgkin/patologia , Humanos , Líbano/epidemiologia , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Retrospectivos , Resultado do Tratamento , Vimblastina/uso terapêutico , Adulto Jovem
13.
Biomed Pharmacother ; 149: 112901, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-36068771

RESUMO

Despite enormous development in the field of drug development, cancer still remains elusive. Compromised immunity stands as a roadblock to the successful pharmacological execution of anti-cancer drugs used clinically currently. Recently some breakthrough cancer treatment strategy like nano-formulation, extracellular vesicles treatment, natural antioxidant therapy, targeted immunotherapy, gene therapy, thermal ablation and magnetic hyperthermia, and pathomics and radiomics has been developed and tested pre-clinically as well as clinically. However, clinical efficacy of such therapies is yet to establish and some are too costly to be utilized by patients from poor and developing countries. At this juncture, researchers are heading towards the search of medicines from natural sources that is higher safety margin and multitarget pharmacological efficacy compared to conventional treatments. Mushroom is used traditionally as food as well as drug since time immemorial due to its immunomodulatory effect which is loaded with proteins, low fat content and cholesterol. Mushrooms are recommended as one of the best vegetarian diets for immunosuppressed cancer and HIV/AIDS patients. Mushrooms are well-known for their anti-cancer activity that impacts hematopoietic stem cells, lymphocytes, macrophages, T cells, dendritic cells (DCs), and natural killer (NK) cells in the immune system. This comprehensive review article emphasizes on the molecular mechanisms of cancer genesis, conventional anti-cancer therapy as well as reported some significant breakthrough in anti-cancer drug development, anti-cancer activity of some selected species of mushrooms and their bioactive phytoconstituents followed by a brief discussion of recent anti-cancer efficacy of some metallic nanoparticles loaded with mushrooms.


Assuntos
Agaricales , Antineoplásicos , Neoplasias , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Humanos , Imunidade , Imunoterapia , Neoplasias/tratamento farmacológico
14.
ChemMedChem ; 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36111583

RESUMO

We identified 2,4-dinitro-biphenyl-based compounds as new inhibitors of leukotriene C4 synthase (LTC4S) and 5lipoxygenase-activating protein (FLAP), both members of the "membrane associated proteins in eicosanoid and glutathione metabolism" (MAPEG) family involved in the biosynthesis of proinflammatory eicosanoids. By molecular docking we evaluated the putative binding against the targets of interest, and by applying cellfree and cell-based assays we demon-strate inhibition of LTC4S and FLAP by the small molecules at low micromolar concentrations. The present results integrate the previously observed inhibitory profile of the tested compounds against another MAPEG member, i.e., microsomal pros-taglandin E2 synthase (mPGES)-1, suggesting that the 2,4-dinitro-biphenyl scaffold is a suitable molecular platform for a multitargeting approach to modulate pro-inflammatory mediators in inflammation and cancer treatment.

15.
Curr Med Chem ; 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36111760

RESUMO

Tyrosinase is a bifunctional polyphenol oxidase (PPO), catalyzing two oxidative reactions: monophenols to o-quinones (monophenolase activity) and o-diphenols to o-quinones (diphenolase activity). As tyrosinase is the rate-limiting enzyme for the melanogenesis process, it is an attractive target for melanogenesis inhibition. Aiming at skin whitening, anticancer, Parkinson's disease (PD) treatment, antibacterial, fruit and vegetable preservation and other anti-pigmentation effect, medicinal chemists have exploited diverse tyrosinase inhibitors through various approaches. In addition to discovering inhibitors with novel scaffold, good activity and high safety, researchers also focused on developing strategies for synergistic effects of multiple inhibitors and simultaneously regulating multiple targets to treat cancer or neurodegenerative diseases. This review focused on multiple natural and synthetic tyrosinase inhibitors which could contribute to preventing fruit and vegetable browning, skin whitening, antibacterial, anticancer, Parkinson's Disease etc.

16.
Artif Intell Med ; 131: 102349, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36100346

RESUMO

Cancer is a Toxic health concern worldwide, it happens when cellular modifications cause the irregular growth and division of human cells. Several traditional approaches such as therapies and wet laboratory-based methods have been applied to treat cancer cells. However, these methods are considered less effective due to their high cost and diverse side effects. According to recent advancements, peptide-based therapies have attracted the attention of scientists because of their high selectivity. Peptide therapy can efficiently treat the targeted cells, without affecting the normal cells. Due to the rapid increase of peptide sequences, an accurate prediction model has become a challenging task. Keeping the significance of anticancer peptides (ACPs) in cancer treatment, an intelligent and reliable prediction model is highly indispensable. In this paper, a FastText-based word embedding strategy has been employed to represent each peptide sample via a skip-gram model. After extracting the peptide embedding descriptors, the deep neural network (DNN) model was applied to accurately discriminate the ACPs. The optimized parameters of DNN achieved an accuracy of 96.94 %, 93.41 %, and 94.02 % using training, alternate, and independent samples, respectively. It was observed that our proposed cACP-DeepGram model outperformed and reported ~10 % highest prediction accuracy than existing predictors. It is suggested that the cACP-DeepGram model will be a reliable tool for scientists and might play a valuable role in academic research and drug discovery. The source code and the datasets are publicly available at https://github.com/shahidakbarcs/cACP-DeepGram.


Assuntos
Redes Neurais de Computação , Peptídeos , Sequência de Aminoácidos , Humanos , Software
17.
Electromagn Biol Med ; : 1-10, 2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36154345

RESUMO

We recently reported shrinkage of untreatable recurrent glioblastoma (GBM) in an end-stage patient using noninvasive brain stimulation with a spinning oscillating magnetic field (sOMF)-generating device called the Oncomagnetic device. Our in vitro experiments demonstrated selective cancer cell death while sparing normal cells by sOMF-induced increase in intracellular reactive oxygen species (ROS) levels due to magnetic perturbation of mitochondrial electron transport. Here, we describe the results of an in vivo study assessing the toxicity of chronic sOMF stimulation in mice using a newly constructed apparatus comprised of the sOMF-generating active components of the Oncomagnetic device. We chronically stimulated 10 normal 60-day old female C57BL/6 mice in their housing cages for 2 h 3 times a day, as in the patient treatment protocol, over 4 months. We also studied the effects of 2-h acute sOMF stimulation. Our observations and those of blinded independent veterinary staff observers, indicated no significant adverse effects of chronic or acute sOMF stimulation on the health, behavior, electrocardiographic and electroencephalographic activities, hematologic profile, and brain and other tissue and organ morphology of treated mice compared to age-matched untreated control mice. These findings suggest that short- and long-term therapies with the Oncomagnetic device are safe and well tolerated.

18.
Crit Rev Food Sci Nutr ; : 1-29, 2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36154353

RESUMO

Fatty acids are good energy sources (9 kcal per gram) that aerobic tissues can use except for the brain (glucose is an alternative source). Apart from the energy source, fatty acids are necessary for cell signaling, learning-related memory, modulating gene expression, and functioning as cytokine precursors. Short-chain fatty acids (SCFAs) are saturated fatty acids arranged as a straight chain consisting minimum of 6 carbon atoms. SCFAs possess various beneficial effects like improving metabolic function, inhibiting insulin resistance, and ameliorating immune dysfunction. In this review, we discussed the biogenesis, absorption, and transport of SCFA. SCFAs can act as signaling molecules by stimulating G protein-coupled receptors (GPCRs) and suppressing histone deacetylases (HDACs). The role of SCFA on glucose metabolism, fatty acid metabolism, and its effect on the immune system is also reviewed with updated details. SCFA possess anticancer, anti-diabetic, and hepatoprotective effects. Additionally, the association of protective effects of SCFA against brain-related diseases, kidney diseases, cardiovascular damage, and inflammatory bowel diseases were also reviewed. Nanotherapy is a branch of nanotechnology that employs nanoparticles at the nanoscale level to treat various ailments with enhanced drug stability, solubility, and minimal side effects. The SCFA functions as drug carriers, and nanoparticles were also discussed. Still, much research was not focused on this area. SCFA functions in host gene expression through inhibition of HDAC inhibition. However, the study has to be focused on the molecular mechanism of SCFA against various diseases that still need to be investigated.

19.
Curr Med Chem ; 2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36154583

RESUMO

Multi-targeted agents can interact with multiple targets sequentially, resulting in synergistic and more effective therapies for several complicated disorders, including cancer, even with relatively modest activity. Histone deacetylase (HDAC) inhibitors are low molecular weight small compounds that increase the acetylation of histone and non-histone proteins, altering gene expression and thereby impacting angiogenesis, metastasis, and apoptosis, among other processes. The HDAC inhibitors affect multiple cellular pathways thus produce adverse issues, causing therapeutic resistance and they have poor pharmacokinetic properties. The designing of HDAC based dual/multi-target inhibitor is an important strategy to overcome adverse effects, drug resistance and increase the effectiveness in controlling cancer. The selection of target combinations to design multitarget HDACinhibitor is generally accomplished on the basis of systematic high-throughput screening (HTS), network pharmacology analysis methods. The identification of the pharmacophore against individual targets is performed using rational or computation methods. The identified pharmacophore can combine with merged, fused, linked with the cleavable or non-cleavable linker to retain the interaction with the original target while being compatible with the other target.The objective of this review is to elucidate the designing strategies of the potential targets along with biological activity and recent development of dual/multi-targeting HDAC inhibitors as potential anticancer agents.This review elucidate the designing strategies of the potential target along with biological activity and recent development of dual/multi-targeting HDAC inhibitors as potential anticancer agents. The development of HDAC-based dual/multi-target inhibitors is an important approach for overcoming side effects, drug resistance, and effective cancer control.

20.
Phytochemistry ; : 113450, 2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36162462

RESUMO

Five mono-tetrahydrofuran acetogenins: uvamicranins A-E and three known mono-tetrahydrofuran acetogenins; reticulatacin, calamistrin A, and uvarigrin, were isolated from the stems of Uvaria micrantha (Annonaceae). Their structures were elucidated by 2D NMR and high-resolution mass spectral analysis. The absolute configurations of uvamicranins A and B were determined by modified Mosher's method. Evaluation of antiproliferative activity of the isolated compounds showed that they were more potent towards the human hepatocellular carcinoma cell line HepG2, compared to the five other tested cell lines. Among the tested compounds, uvamicranin B (UvB) and uvarigrin (Uv) possessed strong antiproliferative activity with IC50 values of 2.89 ±â€¯0.71 µM and 0.37 ±â€¯0.06 µM, respectively. The antiproliferative mechanism of UvB and Uv, was investigated in HepG2 cell line showing that both compounds marginally induced apoptotic cell death, but exhibited cytostatic effect through induction of cell cycle arrest at the G2/M phase.

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