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1.
World J Exp Med ; 14(3): 96269, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39312702

RESUMO

Esophageal squamous cell carcinoma (ESCC) is a substantial global health burden. Immune escape mechanisms are important in ESCC progression, enabling cancer cells to escape the surveillance of the host immune system. One key player in this process is the Aryl Hydrocarbon Receptor (AhR), which influences multiple cellular processes, including proliferation, differentiation, metabolism, and immune regulation. Dysregulated AhR signaling participates in ESCC development by stimulating carcinogenesis, epithelial-mesenchymal transition, and immune escape. Targeting AhR signaling is a potential therapeutic approach for ESCC, with AhR ligands showing efficacy in preclinical studies. Additionally, modification of AhR ligands and combination therapies present new opportunities for therapeutic intervention. This review aims to address the knowledge gap related to the role of AhR signaling in ESCC pathogenesis and immune escape.

2.
Bioorg Chem ; 153: 107822, 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39305609

RESUMO

Carbonic anhydrase II (CA II) is crucial for maintaining homeostasis in several processes, including respiration, lipogenesis, gluconeogenesis, calcification, bone resorption, and electrolyte balance. It is a pivotal druggable target which is implicated in glaucoma, renal, gastric, and pancreatic carcinomas, as well as in malignant brain tumours. Therefore, to identify new CA II (bovine) inhibitors, the current study was designed to synthesize a library of 20 new triazole-linked hydrazones (6a-t). All compounds were characterized by using spectroscopic techniques such as NMR and mass spectrometry. The in-vitro evaluation resulted in impressive inhibitory capability against CA II with IC50 values ranging from 9.10 ± 0.26-48.26 ± 1.30 µM. Among all derivatives, compounds 6a, 6b, 6d, 6k-6m, 6q, 6s and 6t exhibited potent inhibitory potential with 6t deemed as the most active inhibitor. Additionally, kinetic study of the hybrid 6t revealed concentration dependent type of inhibition with Ki value 7.24 ± 0.0086 µM. Furthermore, molecular docking of 6t correlates well with the kinetic analysis. The in-silico ADMET indicated that most of the synthesized compounds have properties conducive to drug development.

3.
Heliyon ; 10(17): e36895, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39286085

RESUMO

Essential oils are key ingredients in the development of edible films and provide a diverse approach to improving food preservation, as well as sensory qualities. The pectin and kappa-carrageenan composite films were obtained by adding peppermint essential oil in different quantities. The films after their fabrication were thoroughly evaluated for their attributes, which included mechanical, barrier, optical, chemical, thermal, and antioxidant properties. The visual assessment of the films demonstrated that PEO-loaded films showed a uniform, homogenous, and slightly yellowish appearance. There was an increase in the thickness (0.045 ± 0.006 to 0.060 ± 0.008 mm), elongation at break (12.73 ± 0.74 to 25.05 ± 1.33 %), and water vapor permeability (0.447 ± 0.014 to 0.643 ± 0.014 (g*mm)/(m2*h*kPa)) was observed with the addition of PEO. However, tensile strength (45.84 ± 3.69 to 29.80 ± 2.10 MPa) and moisture content (25.83 ± 0.046 to 21.82 ± 0.23 %) decreased with the incorporation of PEO. Furthermore, thermal and antioxidant properties were enhanced by the inclusion of PEO. The presented investigation can be employed to synthesize food packaging material with antioxidant properties with potential applications in food packaging.

4.
RSC Adv ; 14(39): 28524-28542, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39247501

RESUMO

Developing new anti-tyrosinase drugs seems crucial for the medical and industrial fields since irregular melanin synthesis is linked to the resurgence of several skin conditions, including melanoma, and the browning of fruits and vegetables. A novel series of N-1 and C-3 substituted indole-based thiosemicarbazones 5(a-r) are synthesized and further analyzed for their inhibition potential against tyrosinase enzyme through in vitro assays. The synthesized compounds displayed very good to moderate inhibition with half maximal inhibitory concentration in the range of 12.40 ± 0.26 µM to 47.24 ± 1.27 µM. Among all the derivatives 5k displayed the highest inhibitory activity. According to SAR analysis, the derivatives with 4-substitution at the benzyl or phenyl ring of the thiosemicarbazones exhibited better inhibitory potential against tyrosinase. In silico analysis (including ADMET prediction and molecular docking) was conducted and compared with the standard drug (kojic acid). These findings may help the hunt for new melanogenesis inhibitors that the food and cosmetics industries may find valuable.

5.
Curr Top Med Chem ; 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39171593

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Due to the high prevalence of cancer, researchers for the past decades have made considerable efforts for its management and treatment. Medicinal plants have always been exploited to discover novel anticancer agents. Oman's huge biodiversity has created a rich source of traditional medicine. OBJECTIVE: The current survey has aimed to document the traditionally used medicinal plants of Oman and their therapeutic role in the treatment of cancer. MATERIAL METHOD: This study comprises of literature-based survey through different databases, including Google, Scopus, Google Scholar, Web of Science, Science Direct, Springer Link, BioMed Central and PubMed. RESULTS: The current review revealed a total of 57 plant species that belong to 35 families that are used in the treatment of cancer in Oman. Most documented plants belong to Solanaceae (6 sp.), Apocyanaceae (5 sp.) and Lamiaceae (4 sp.). The literature reveals that the residents of the area mostly use leaves (38.5%) and prepare their recipes in the form of decoction (40.3%). Moreover, herbs are the most dominant life form (43.85%). Among all forms of cancer in Oman, breast (47%), wound (26), and lung cancer (0.5%) were found dominantly. A literature study confirmed that the medicinal plants used for cancer in Oman are rich in phytochemicals such as quercetin, allicin, coumarin, alliin, kaempferol, solamargine, rutin, lupeol, ursolic acid and luteolin that have shown significant biological activities including anti-cancer potential. It reflects the efficacy of these plants to be used as a medicine in clinical trials. Among all, Boswellia sacra Flueck. is of key importance due to the presence Boswellic acid being used for the treatment of different types of cancer. CONCLUSION: The residents of Oman have great knowledge about the traditional use of medicinal plants for the treatment of various diseases like cancer. The therapeutic potential and physiological efficacy of Omani medicinal plants should be further explored at a molecular level via in vivo and in vitro experiments.

6.
Curr Med Chem ; 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39069711

RESUMO

BACKGROUND: Aerobic glycolysis is crucial for cancer cells to survive, grow, and progress. In the current study, the anti-cancer effects of astragalin (ASG) on breast cancer cells and in the glycolytic pathway through AMPK/mTOR have been evaluated. OBJECTIVE: The objective of this study was to examine the impact of ASG, a natural flavonoid, on glycolysis via targeting AMPK/mTOR signalling in MDA-MB-231 breast cancer cells. METHOD: The study utilized ASG, which was isolated from Haplophyllum tuberculatum. The cells were treated with different concentrations of ASG (20 and 40 µg/mL), and anti- glycolytic activities were measured through cell proliferation, expression of glycolytic enzymes (HK-2, LDH-A, GLUT-1), glucose uptake, and lactate concentration assays. The MTT assay was used to assess cellular proliferation, while the glucose uptake and lactate levels were determined by employing colorimetric assays. The mRNA expression of target glycolytic enzymes was determined by qRT-PCR. The protein levels of glycolytic targets, as well as that of AMPK and mTOR, were determined by western blot. in silico docking of ASG was done with mTOR and AMPK proteins. RESULT: Astragalin exhibited dose- and time-dependent anti-proliferative effects in MDA-MB-231 cells. In breast cancer cells, the mRNA and protein expression of GLUT-1, LDH-A, and HK-2 were all significantly downregulated after receiving ASG treatments. Furthermore, after ASG treatments, MDA-MB231 cells showed a significant decrease in lactate and glucose uptake compared to control cells. Mechanistically, ASG increased AMPK activation and suppressed mTOR activation in these cells. The inhibitory role of ASG on aerobic glycolysis was prevented by treatments with compound C (an AMPK inhibitor). However, combined treatment of compound C and ASG could nullify the ASG-induced anti-glycolysis effect and restore the level of p-AMPK and p-mTOR in MDA-MB231 cells. The results from molecular docking predicted that ASG had the potential to bind AMPK and mTOR, with free energy for binding, -8.2 kcal/mol and -8.1 kcal/mol, respectively. CONCLUSION: Taken together, the findings from this study indicated that ASG might modulate the AMPK/mTOR pathway to inhibit aerobic glycolysis and proliferation of MDAMB231 breast cancer.

7.
Sci Rep ; 14(1): 12475, 2024 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-38816444

RESUMO

Sirtuin 3 (SIRT3) belongs to the Sirtuin protein family, which consists of NAD+-dependent lysine deacylase, involved in the regulation of various cellular activities. Dysregulation of SIRT3 activity has been linked to several types of cancer, including breast cancer. Because of its ability to stimulate adaptive metabolic pathways, it can aid in the survival and proliferation of breast cancer cells. Finding new chemical compounds targeted towards SIRT3 was the primary goal of the current investigation. Virtual screening of ~ 800 compounds using molecular docking techniques yielded 8 active hits with favorable binding affinities and poses. Docking studies verified that the final eight compounds formed stable contacts with the catalytic domain of SIRT3. Those compounds have good pharmacokinetic/dynamic properties and gastrointestinal absorption. Based on excellent pharmacokinetic and pharmacodynamic properties, two compounds (MI-44 and MI-217) were subjected to MD simulation. Upon drug interaction, molecular dynamics simulations demonstrate mild alterations in the structure of proteins and stability. Binding free energy calculations revealed that compounds MI-44 (- 45.61 ± 0.064 kcal/mol) and MI-217 (- 41.65 ± 0.089 kcal/mol) showed the maximum energy, suggesting an intense preference for the SIRT3 catalytic site for attachment. The in-vitro MTT assay on breast cancer cell line (MDA-MB-231) and an apoptotic assay for these potential compounds (MI-44/MI-217) was also performed, with flow cytometry to determine the compound's ability to cause apoptosis in breast cancer cells. The percentage of apoptotic cells (including early and late apoptotic cells) increased from 1.94% in control to 79.37% for MI-44 and 85.37% for MI-217 at 15 µM. Apoptotic cell death was effectively induced by these two compounds in a flow cytometry assay indicating them as a good inhibitor of human SIRT3. Based on our findings, MI-44 and MI-217 merit additional investigation as possible breast cancer therapeutics.


Assuntos
Neoplasias da Mama , Simulação de Acoplamento Molecular , Sirtuína 3 , Sirtuína 3/metabolismo , Sirtuína 3/antagonistas & inibidores , Sirtuína 3/química , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Feminino , Linhagem Celular Tumoral , Simulação de Dinâmica Molecular , Antineoplásicos/farmacologia , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/farmacologia , Bibliotecas de Moléculas Pequenas/química , Proliferação de Células/efeitos dos fármacos , Ligação Proteica
8.
Biol Trace Elem Res ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38656680

RESUMO

Tobacco smoking is becoming one of the major worldwide concerns regarding environmental pollution as well as health threats. In 2005, the World Health Organization (WHO) released the Framework Convention On Tobacco Control (FCTC), which outlined protocols for controlling tobacco products. Oman was one of the leading countries to follow these protocols; however, Egypt has only followed these protocols recently in 2020. One of the main challenges in tobacco product control is the variation in their trace element's types and amounts from country to country owing to differences in agriculture techniques and used chemical additives. Smoking releases different toxic metal ions found in them into the air, and hence, analyzing trace amounts of metals in tobacco smoking products is becoming more critical. The proposed research aims to evaluate the current levels of 11 heavy metals (namely, As, Pb, Cd, Co, Cr, Be, Ba, Mn, Ni, Fe, and Hg) in 22 tobacco products available in Egypt and Oman using inductively coupled plasma optical emission spectroscopy and a direct mercury analyzer. Although some elements such as Be, Co, and Cd were absent, the positive detection of As and Pb and the levels of Ba, Cr, and Ni are still alarming, especially for heavy smokers. The obtained results were then statistically related to previously published data in 2017 to explore the effectiveness of implementing the FCTC protocols within the Egyptian market. The outcomes suggested a positive impact of FCTC protocol implementation in Egypt, besides the lower levels of elemental content for Omani products compared to the Egyptian market.

9.
Curr Top Med Chem ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38685780

RESUMO

Berbamine (Ber) is an active medicinal bisbenzylisoquinoline alkaloid, which is usually obtained from different plants of the genus Berberis (family Berberidaceae) and is used to cure various disorders in traditional Chinese and Ayurvedic systems of medicine. Numerous in-vitro and in-vivo studies revealed the apoptotic and cytotoxic potential of Ber against different cell lines (SMMC-7721, A549, MDA-MB-231, and K562) by upregulating pro-apoptotic (Bax, p53) and downregulating anti-apoptotic (Bcl-2, survivin) proteins. Other pharmacological attributes ascribed to Ber included cardioprotective, anti-diabetic, anti-inflammatory, antimalarial, antioxidant, anti-hypercholesterolemic, and anti-allergic. Moreover, the synergistic effect of Ber improved the therapeutic potential of different drugs (paclitaxel (PTL), gemcitabine, dexamethasone, doxorubicin (DOX), and celecoxib) in different models. Various attempts could fabricate biologically active derivatives of Ber, such as 4-chlorobenzoyl berbamine (CBB) and O-4- ethoxyl-butyl-berbamine (EBB). The review focuses on the medicinal applications of Ber, particularly anti-cancer, cardioprotective, and anti-inflammatory, along with the mechanism of action.

10.
Curr Med Chem ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38616761

RESUMO

BACKGROUND/AIM: Glioblastoma is an extensively malignant neoplasm of the brain that predominantly impacts the human population. To address the challenge of glioblastoma, herein, we have searched for new drug-like candidates by extensive computational and biochemical investigations. METHOD: Approximately 950 compounds were virtually screened against the two most promising targets of glioblastoma, i.e., epidermal growth factor receptor (EGFR) and phosphoinositide 3-kinase (PI3K). Based on highly negative docking scores, excellent binding capabilities and good pharmacokinetic properties, eight and seven compounds were selected for EGFR and PI3K, respectively. RESULTS: Among those hits, four natural products (SBEH-40, QUER, QTME-12, and HCFR) exerted dual inhibitory effects on EGFR and PI3K in our in-silico analysis; therefore, their capacity to suppress the cell proliferation was assessed in U87 cell line (type of glioma cell line). The compounds SBEH-40, QUER, andQTME-12 exhibited significant anti-proliferative capability with IC50 values of 11.97 ± 0.73 µM, 28.27 ± 1.52 µM, and 22.93 ± 1.63 µM respectively, while HCFR displayed weak inhibitory potency (IC50 = 74.97 ± 2.30 µM). CONCLUSION: This study has identified novel natural products that inhibit the progression of glioblastoma; however, further examinations of these molecules are required in animal and tissue models to better understand their downstream targeting mechanisms.

11.
ACS Omega ; 9(8): 9003-9012, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38434887

RESUMO

The trends in food packaging technologies are shifting toward utilizing natural and environmentally friendly materials prepared from biopolymers such as kappa carrageenan to replace synthetic polymers. In the current study, varying amounts (0.1, 0.2, and 0.3%) of grapefruit essential oil (GFO) were incorporated in kappa carrageenan-based edible films to improve their physicochemical properties. The developed film samples were characterized for their barrier, mechanical, morphological, optical, thermal, antioxidant, and biodegradable properties. The results obtained showed that the tensile strength of the carrageenan films enhanced significantly from 65.20 ± 4.71 to 98.21 ± 6.35 MPa with the incorporation of GFO in a concentration-dependent manner. FTIR and SEM analysis confirmed the intermolecular bonding between carrageenan and GFO, resulting in the formation of compact films. Incorporating GFO significantly enhanced the thermal resistance of oil-loaded films, as confirmed by TGA, DSC, and DTG analysis. The addition of GFO led to a substantial increase in the radical scavenging activity of the films, as evidenced by the DPPH and ABTS assays. Furthermore, the developed films were biodegradable in soil and seawater environments, indicating their potential as a sustainable alternative to traditional plastics. Findings demonstrated that GFO can be used as a natural antioxidant agent in kappa carrageenan-based films for potential applications in food packaging.

12.
Macromol Biosci ; 24(6): e2300530, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38319279

RESUMO

Postoperative adhesion can cause complications, such as pain and organ blockage, in the abdominal regions. To address this issue, surgical techniques and antiadhesive treatments are applied. Given the significant role of vascularization in adhesion band formation, Avastin (Ava) that targets vascular endothelial growth factor (VEGF) can be applied to prevent peritoneal adhesion bands. Moreover, Alginate (Alg), a natural polysaccharide, is a promising physical barrier to prevent adhesion bands. Incorporating Ava into Alg hydrogel in a form of 3D-printed scaffold (Alg/Ava) has potential to suppress inflammation and angiogenesis, leading to reduce peritoneal adhesion bands. Following physical, morphological, and biocompatibility evaluations, the efficacy of Alg and Ava alone and their combination in Alg/Ava on the formation of postsurgical adhesions is evaluated. Upon confirming physical stability and sustained release of Ava, the Alg/Ava scaffold effectively diminishes both the extent and strength of adhesion bands. Histopathological examination shows that the reduction in fibrosis and inflammation is responsible for preventing adhesion bands by the Alg/Ava scaffold. Additionally, the cytokine assessment reveals that this is due to the inhibition in the secretion of VEGF and Interleukin 6 suppressing vascularization and inflammatory pathways. This study suggests that a 3D-printed Alg/Ava scaffold has great potential to prevent the postsurgical adhesion bands.


Assuntos
Alginatos , Bevacizumab , Impressão Tridimensional , Alicerces Teciduais , Fator A de Crescimento do Endotélio Vascular , Alginatos/química , Alginatos/farmacologia , Aderências Teciduais/prevenção & controle , Animais , Alicerces Teciduais/química , Bevacizumab/farmacologia , Bevacizumab/química , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ratos , Complicações Pós-Operatórias/prevenção & controle , Humanos , Hidrogéis/química , Hidrogéis/farmacologia
13.
Heliyon ; 10(3): e25501, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38371972

RESUMO

This research focused on the development of films based on pectin and xanthan gum composite loaded with different concentrations of grapefruit essential oil (GFO). The fabricated films were characterized to assess the effect of GFO on the structural, mechanical, barrier, chemical, and antioxidant properties. The addition of GFO enhanced the functional properties of the films, as confirmed by FTIR analysis showing molecular interactions within the film matrix. SEM observations revealed that films with higher GFO content had a smoother, more compact structure with uniform oil distribution. Films loaded with oil demonstrated enhanced water resistance, as their decreased permeability ranged from 0.733 ± 0.009 to 0.561 ± 0.020 (g mm)/(m2.h.kPa). Additionally, these films showed a notable increase in tensile strength, ranging from 2.91 ± 0.19 to 8.55 ± 0.62 MPa. However, the addition of oil led to a reduction in the elongation at break of the films, which decreased from 52.84 ± 3.41 % to 12.68 ± 1.52 %, and a decline in transparency from 87.57 ± 0.65 % to 76.18 ± 1.12 %. Fabricated films exhibited enhanced antioxidant properties, as evidenced by increased DPPH• and ABTS•+ radical scavenging activities with the addition of GFO. The findings of the current study suggest that GFO is an effective natural additive for enhancing the physiochemical properties of pectin and xanthan gum-based films, making them more suitable for food packaging applications.

14.
Int J Biol Macromol ; 264(Pt 2): 130463, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38423442

RESUMO

Sodium tripolyphosphate (STPP), an inorganic and non-toxic polyphosphate, has potential applications as a crosslinking agent in the fabrication of edible films. This study utilized STPP in the development of sodium alginate-chitosan composite films, with a focus on their suitability for food packaging applications. The results indicate that the incorporation of STPP led to an increase in film thickness (from 0.048 ± 0.004 to 0.078 ± 0.008 mm), elongation at break (from 11.50 ± 1.49 % to 15.88 ± 2.14 %), water permeation (from 0.364 ± 0.010 to 0.521 ± 0.021 gmm/(m2h*kPa)), and moisture content (from 25.98 ± 0.20 % to 28.12 ± 0.17 %). In contrast, there was a decrease in tensile strength (from 30.23 ± 2.08 to 25.60 ± 1.22 MPa) and swelling index (from 752.9 ± 17.1 to 533.5 ± 8.9 %). Scanning electron microscopy (SEM) analysis revealed the formation of distinctive needle-like microcrystals with the incorporation of STPP. Fourier-transform infrared spectroscopy (FTIR) analysis indicated intermolecular interactions between STPP and the film-forming biopolymers. The data obtained from Thermogravimetric analysis (TGA) and Differential Scanning Calorimetry (DSC) demonstrated enhanced thermal stability of STPP-loaded films at elevated temperatures. Furthermore, the films exhibited increased DPPH scavenging activity with the addition of STPP. This study underscores the potential of STPP as a crosslinking agent for the development of composite edible films, suggesting applications in the field of food packaging.


Assuntos
Alginatos , Quitosana , Alginatos/química , Quitosana/química , Resistência à Tração , Polifosfatos , Embalagem de Alimentos
15.
Food Sci Nutr ; 12(2): 1056-1066, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38370062

RESUMO

Boswellia sacra and its derivatives exhibit notable bioactive properties, which have been the subject of extensive scientific research; however, their potential applications in food packaging remain largely untapped. In the current study, cellulose, sodium alginate, and gelatin composite edible films were fabricated with the addition of different concentrations (0.2% and 0.3%) of the ethanolic fraction of Boswellia sacra oleo gum resin (BSOR). The resultant films were examined for their physical, chemical, mechanical, barrier, optical, and antioxidant properties. Moreover, the films were characterized using Scanning Electron Microscopy (SEM), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR) to study the impact of incorporating BSOR on the morphological, crystalline, and chemical properties of the films. The addition of BSOR increased the film thickness (0.026-0.08 mm), water vapor permeability (0.210-0.619 (g.mm)/(m2.h.kPa), and the intensity of the yellow color (3.01-7.20) while reducing the values of both tensile strength (6.67-1.03 MPa) and elongation at break (83.50%-48.81%). SEM and FTIR analysis confirmed the interaction between the BSOR and film-forming components. The antioxidant properties of the edible films were significantly increased with the addition of BSOR. The comprehensive findings of the study demonstrated that BSOR possesses the potential to serve as an efficient natural antioxidant agent in the fabrication of edible films.

16.
Mycopathologia ; 189(1): 12, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38231359

RESUMO

Basidiobolomycosis is an uncommon fungal infection caused by the genus Basidiobolus. In immunocompetent children, it usually causes cutaneous infection and rarely affects the gastrointestinal tract, and it is extremely rare for the disease to spread. The present study reports the first case of disseminated basidiobolomycosis caused by Basidiobolus omanensis in a child with acute lymphoblastic leukemia who died as a result of uncontrolled infection and multi-organ failure despite surgical and antifungal therapy with L-AMB and voriconazole. A review of the literature yielded 76 cases, including the current case with the majority of which were reported as invasive gastrointestinal infection. The median age was 4 years (61 male and 15 female) and the majority of these children were from the Middle East (80%), specifically Saudi Arabia (45%). Most patients were treated with systemic antifungal agents (mostly itraconazole and amphotericin B). Surgical intervention was done in 25% of these patients and the death rate was 12%.


Assuntos
Entomophthorales , Leucemia-Linfoma Linfoblástico de Células Precursoras , Zigomicose , Criança , Humanos , Feminino , Masculino , Pré-Escolar , Zigomicose/diagnóstico , Zigomicose/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Itraconazol/uso terapêutico
17.
Int J Biol Macromol ; 255: 128259, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37984572

RESUMO

In several types of cancers, the expression of carbonic anhydrase-IX (CA-IX) enzyme is elevated than its normal level which ultimately plays a key role in the tumor growth of epithelial cells in breast and lung cancer by acidifying tumor microenvironment, therefore, inhibition of this target is important in antitumor therapy. We have synthesized bis-benzimidazole derivatives (1-25) by using 3,3'-diaminobenzidine and various aromatic aldehydes and characterized by various spectroscopic methods (UV/Visible, 1HNMR, 13CNMR, and mass spectrometry). Their inhibitory potential for human CA-IX (hCA-IX) was evaluated in-vitro, where several synthesized derivatives showed potent inhibition of hCA-IX (IC50 values in range of 5.23 ± 1.05 to 40.10 ± 1.78 µM) and compounds 3-5, 7-8, 13-16, 21 and 23 showed superior activity than the standard drug "acetazolamide" (IC50 = 18.24 ± 1.43 µM). Furthermore, all these compounds showed no toxicity on human fibroblast cell lines (BJ cell lines). Moreover, molecular docking was carried out to predict their binding modes in the active site of CA-IX and revealed a significant role of imidazole ring of synthesized entities in their effective binding with the specific residues of CA-IX. The obtained results paved the way for further in vivo and other pharmacological studies for the optimization of these molecules as possible anti-cancer agents.


Assuntos
Antineoplásicos , Anidrases Carbônicas , Neoplasias , Humanos , Anidrases Carbônicas/química , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade , Antineoplásicos/química , Neoplasias/tratamento farmacológico , Inibidores da Anidrase Carbônica/química , Estrutura Molecular , Microambiente Tumoral
18.
Int J Biol Macromol ; 254(Pt 3): 128045, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37956812

RESUMO

In the current study, sodium caseinate and chitosan-based composite edible films were developed with the incorporation of black pepper (Piper nigrum) essential oil (BPO) in various concentrations (0.05, 0.1 and 0.15 %) for potential food packaging applications. The chemical composition of BPO was determined using GCMS and the major compound detected were ß-caryophyllene, limonene, ß-phellandren, pinene, copaene and α-humulene. The addition of BPO resulted in an increase in the thickness, EAB, WVP, moisture content and swelling index values of the films; however, the TS and water solubility decreased. The inclusion of BPO led to a substantial enhancement in the DPPH and ABTS radical scavenging capabilities of the edible films. SEM micrographs demonstrated intermolecular interaction between BPO, sodium caseinate, and chitosan. FTIR spectra confirmed the interaction of the functional groups of the polymers and BPO. The incorporation of the BPO increased the crystallinity of the films. Moreover, the thermal analysis including TGA, DSC and DTG demonstrated an increase in the thermal stability of the edible films with the addition of the BPO. These findings demonstrated that sodium caseinate and chitosan composite based edible films loaded with BPO can be used as sustainable active food packaging material.


Assuntos
Quitosana , Filmes Comestíveis , Óleos Voláteis , Piper nigrum , Quitosana/química , Antioxidantes/química , Caseínas , Embalagem de Alimentos/métodos
19.
Heliyon ; 9(11): e22483, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38074891

RESUMO

Neurodegenerative complications, like Alzheimer's disease (AD) exert adverse effects i.e. psychological and physiological in the central nervous system. The synthetic drugs used for these complications have negative effects on body health and therefore natural remedies are a good and targeted approach to counter such complications. Alternatively, fruits and a variety of biochemicals which are an important source of diet, can be used for remedial purposes. Due to the antioxidant properties of polyphenolic compounds, several companies utilize this property to advertise polyphenol-rich beverages. Pomegranate (Punica granatum L.), is one such fruit that is well known for its medical usage due to its antioxidant properties. In the cuurent study a literature search survey was performed on traditional uses, phytochemicals on pomegranate and their medical applications especaily in neurodegenerative deasese using electronic data bases like PubMed, Google Scholar, Scopus, Science Direct Wikipedia and Springer Nature. Based on previous preclinical and clinical studies, pomegranate juice, extracts, and its bioactive constituents have shown many mitigating properties, including suppression of inflammatory cell signaling, reduction in expression of genes associated with oxidative stress as well as pro-inflammatory cytokines in neurons, decreased production of inflammatory and oxidative stress biomarkers and increased expression of endothelial nitric oxide synthase. It also decreases the expression of soluble amyloid protein procurer ß (sAPPß), ß-secretase and carboxyl terminal fragment ß (CTFß). Similarly, during an in-vivo study on APP/PS1 mice, pomegranate supplementation has been shown to impart cognitive aid by the protection of neurons and triggering neurogenesis through anti-inflammatory signaling pathway. In conclusion, pomegranate supplementation can be a promising source of protection against Alzheimer's disease.

20.
Saudi Pharm J ; 31(12): 101877, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38075546

RESUMO

Utilizing multi-target drugs shows great promise as an effective strategy against polygenic diseases characterized by intricate patho-mechanisms, such as ulcers, skin dermatitis, and cancers. The current research centers around the creation of hybrid compounds, connecting dibenzazepine and isoxazole, with the aim of exploring their potential as inhibitors for urease and tyrosinase enzymes. Analogs 6a, 6b, 6d, 6 h-6j, and 6 l demonstrated strong inhibitory potential against tyrosinase enzyme with IC50 values of 4.32 ± 0.31-12.36 ± 0.48. Whereas analogs 6a, 6c, 6e, 6f, 6h-6m, and 6r exhibited potent inhibitory activities against urease enzyme with IC50 values of 3.67 ± 0.91-15.60 ± 0.18 µM. Furthermore, compounds 6i, 6n, and 6r showed weak toxic effect in BJ-cell line, whereas the remaining compounds were found non-toxic to normal cell line. The mechanistic studies of potent inhibitors of both the enzymes showed competitive mode of inhibition. Molecular docking was employed to establish the relationship between structure and activity and to elucidate the interaction mechanism. This analysis revealed that the active analogs exhibited crucial interactions with the active site residues of urease and tyrosinase, thus corroborating our experimental results. Hence, the generated derivatives of dibenzazepine-linked isoxazoles present intriguing starting points for further investigations into their potential as inhibitors of urease and tyrosinase, with the potential for future modification and enhancement.

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