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1.
Heliyon ; 10(7): e28598, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38576579

RESUMEN

Fish farming in homestead ponds help alleviate poverty, provide animal source food, micronutrients, and indirect income and various jobs in developing nations. This study investigated the impact of homestead pond fish farming on dietary diversity (HDDS and MDD-W), food security (HFIAS and ELCSA), income, and women's engagement. A total of 185 households were selected randomly for data collection through well-structured questionnaire interviews in the central coast of Bangladesh. HDDS revealed significant dietary diversity (73.3%) among beneficiary farmers, surpassing controls and nearly doubling that of non-aquaculture farmers (41.1%). Additionally, this study found that 86.7% and 74.3% of women in beneficiary and homestead pond farmers exhibited high dietary diversity (MDD-W ≥ 5), whereas 48.6% of women in non-aquaculture farmers' households had low dietary diversity (MDD-W ≥ 5). Based on both ELCSA and HFIAS, higher prevalence of food security was observed among the beneficiary farmers that was about 60% and 63.3%, respectively compared with the control farmers. Most non-aquaculture farmers (62.9%) indicated their family consumed fish for one week before the research. More than half of the homestead pond culture (55.7%) and more than 90% of the beneficiary farmers, aquaculture farmers and non-aquaculture farmers had gross income (<$ 500). Pertaining to women's participation in homestead pond was positively correlated to productivity while male dominated tasks was negatively correlated with productivity. The results offer insights into how homestead pond fish farming can enhance food security by supplying direct animal protein, addressing protein and micronutrient deficiencies, and boosting income. The study emphasizes the urgent necessity for training and promoting homestead pond culture, increasing female participation, and advocating comprehensive support from governmental organizations (GOs) and non-governmental organizations (NGOs) to optimize production, improve micronutrient adequacy, and guarantee household food security. Keywords: Fish farming, food security, dietary diversity, women's participation.

2.
Molecules ; 29(8)2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38675628

RESUMEN

In this study, we present a comprehensive investigation of 2-amino-4,6-diphenylnicotinonitriles (APNs, 1-6), including their synthesis, cytotoxicity against breast cancer cell lines, and photophysical properties. Compound 3 demonstrates exceptional cytotoxicity, surpassing the potency of Doxorubicin. The fluorescence spectra of the synthesized 1-6 in different solvents reveal solvent-dependent shifts in the emission maximum values, highlighting the influence of the solvent environment on their fluorescence properties. A quantum chemical TD-DFT analysis provides insights into the electronic structure and fluorescence behavior of 1-6, elucidating HOMO-LUMO energy gaps, electronegativity values, and dipole moments, contributing to a deeper understanding of their electronic properties and potential reactivity. These findings provide valuable knowledge for the development of APNs (1-6) as fluorescent sensors and potential anticancer agents.


Asunto(s)
Antineoplásicos , Nitrilos , Humanos , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Nitrilos/química , Nitrilos/síntesis química , Nitrilos/farmacología , Línea Celular Tumoral , Teoría Cuántica , Estructura Molecular , Espectrometría de Fluorescencia , Células MCF-7 , Supervivencia Celular/efectos de los fármacos
3.
Heliyon ; 10(6): e27639, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38496892

RESUMEN

Graphene has recently drawn exponential attention due to its surprising physicochemical properties and diversified field of applications. Although graphene oxides (GOs), itself is an exclusive material, it is also an intermediate product for the production of reduced graphene oxides (rGOs), graphene and their derivatives, which are other more superficial materials. In this study, GOs with higher oxygen to carbon ratios were synthesized following the Tour method, where the excess feed acid liquor (FAL) of mixed concentrated sulfuric and orthophosphoric acids at a ratio of 90:10 was recovered from the reaction slurries by applying the centrifugation technique. About 80-90 % of the FAL was recycled and reused as feed for the subsequent batches. The changes in the properties of FAL for the five consecutive recycling and reuse were studied. The properties of recycled FALs were investigated by measuring density, moisture content, pH, and ion concentration. The consecutive recycling of FALs tends to increase the moisture content about 0.5% in each recycles. Ion-chromatography (IC) was used to measure the variation in SO42- and PO43- ions in the FALs. The H2SO4 reacts with KMnO4 and crystalized out from the recovered FAL faster than the phosphoric acid. So, sulfuric acid content in the makeover FALs must be greater than primary FAL. The product GOs were characterized using FT-IR, FT-Raman, UVVis, STA, SEM, XPS, Zeta-potential, and particle size analyzers. The variation of the properties of GOs with the changes in the reaction parameters such as temperature and time were investigated and correlated with the product yield. It was observed that the effect of temperature on the reaction rate was found to be negatively and positive with the reaction time. The oxygen-to-carbon atomic ratio from XPS analysis was found 66.7%, which supported the increase in product yields 66.9% in the experimental results. The effect of acid concentration, reaction temperature, and time on the GOs properties were satisfactory, correlated, and easily controllable with the reaction conditions. A higher extent of oxidation and enhanced product yields 65-70% were observed at 60-70 °C and 14-18 h. A mixture of nano- and macro-molecular GOs was obtained, and their compositions were easily controllable and separable by controlling the reaction conditions. A correlation was made among the properties of synthesized GOs, FAL, and recycled FAL and reaction conditions.

4.
RSC Adv ; 13(51): 36209-36222, 2023 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-38090093

RESUMEN

The integration of bioactive substances with antibiotics has been extensively pursued for the treatment of osteomyelitis. These materials, also known as biomaterials, can serve both as bone replacements and targeted drug delivery systems for antibiotics. In this study, biomimetic nano-hydroxyapatite (nHAp) was synthesized via the coprecipitation technique where waste chicken eggshell (WCE) was employed as the source of Ca. Heat treatment was performed at four different temperatures (100 °C, 300 °C, 600 °C and 900 °C). Subsequently, the samples were characterized using XRD, FTIR spectroscopy, Raman spectroscopy, FESEM, EDX, XPS, DLS hydrodynamic size and zeta potential analysis. Also, their biomedical effectiveness was evaluated in terms of cytotoxicity, hemolysis, antibacterial performance, and bioactivity. Doxycycline hyclate (DOXh) was loaded in the synthesized nHAp samples, and subsequently its in vitro release was studied under stirring in simulated body fluid (SBF). The DOXh release kinetics was evaluated, and it was found that the first-order model was the best fitted kinetic model describing the release of DOXh from the nHAp samples, except for nHAp100, which was best described by the Korsmeyer-Peppas model. The nHAp synthesized utilizing WCE showed excellent potential for biomedical application and can be used as a drug delivery agent for antibiotics, such as DOXh.

5.
Pharmaceuticals (Basel) ; 16(9)2023 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-37765132

RESUMEN

In the pursuit of developing more potent and effective targeted kinase inhibitors (TKIs), a series of new compounds, specifically halogenated '(E)-4-((7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)-N'-benzylidenebenzohydrazides', were successfully synthesized in three steps with high yields. Among these novel compounds, namely 5e, 5h, 5k, and 5l, promising cytotoxic effects were observed against four different cancer cell lines, with IC50 values ranging from 29 to 59 µM. Notably, compound 5k emerged as the most potent inhibitor, exhibiting significant activity against EGFR, Her2, VEGFR2, and CDK2 enzymes, with IC50 values ranging from 40 to 204 nM, comparable to the well-known TKI sunitinib (IC50 = 261 nM). Mechanistic investigations of compound 5k revealed its ability to induce cell cycle arrest and apoptosis in HepG2 cells, accompanied by a notable increase in proapoptotic proteins caspase-3 and Bax, as well as the downregulation of Bcl-2 activity. Furthermore, molecular docking studies indicated similar binding interactions between compound 5k and the four enzymes, as observed with sunitinib. These findings highlight the potential of compound 5k as a promising candidate for further development as a multi-targeted kinase inhibitor with enhanced potency.

7.
Molecules ; 28(13)2023 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-37446696

RESUMEN

Ruthenium (Ru)-based organometallic drugs have gained attention as chemotherapeutic and bioimaging agents due to their fewer side effects and excellent physical optical properties. Tuning the electronic structures of Ru complexes has been proven to increase the cytotoxicity of cancer cells and the luminescent efficiency of the analytical probes. However, the relationship between electronic structures and bioactivities is still unclear due to the potential enhancement of both electron donor and acceptor properties. Thus, we investigated the relationship between the electronic structures of Ru(II) complexes and cytotoxicity by optimizing the electron-withdrawing (complex 1), electron-neutral (complex 2), and electron-donating (complex 3) ligands through DFT calculations, bioactivities tests, and docking studies. Our results indicated that it was not sufficient to consider only either the effect of electron-withdrawing or electron-donating effects on biological activities instead of the total electronic effects. Furthermore, these complexes with electron-donating substituents (complex 3) featured unique "off-on" luminescent emission phenomena caused by the various "HOMO-LUMO" distributions when they interacted with DNA, while complex with electron-withdrawing substituent showed an "always-on" signature. These findings offer valuable insight into the development of bifunctional chemotherapeutic agents along with bioimaging ability.


Asunto(s)
Complejos de Coordinación , Rutenio , Rutenio/química , Piridinas/química , ADN/química , Teoría Funcional de la Densidad , Complejos de Coordinación/farmacología , Complejos de Coordinación/química
8.
Arch Pharm (Weinheim) ; 356(8): e2300185, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37253118

RESUMEN

A series of 16 novel spirooxindole analogs 8a-p were designed and constructed via cost-effective single-step multicomponent [3+2] cycloaddition reaction of azomethine ylide (AY) generated in situ from substituted isatin (6a-d) with suitable amino acids (7a-c) and ethylene-engrafted pyrazole derivatives (5a,b). The potency of all compounds was assayed against a human breast cancer cell line (MCF-7) and a human liver cell line (HepG2). Spiro compound 8c was the most active member among the synthesized candidates, with exceptional cytotoxicity against the MCF-7 and HepG2 cell lines, with IC50 values of 0.189 ± 0.01 and 1.04 ± 0.21 µM, respectively. The candidate 8c exhibited more potent activity (10.10- and 2.27-fold) than the standard drug roscovitine (IC50 = 1.91 ± 0.17 µM (MCF-7) and 2.36 ± 0.21 µM (HepG2)). Compound 8c was investigated for epidermal growth factor receptor (EGFR) inhibition; it exhibited promising IC50 values of 96.6 nM compared with 67.3 nM for erlotinib. The IC50 value of 8c (34.98 nM) exhibited cyclin-dependent kinase 2 (CDK-2) inhibition, being more active than roscovitine the (IC50 = 140 nM) in targeting the CDK-2 kinase enzyme. Additionally, for apoptosis induction of compound 8c in MCF-7, it upregulated the expression levels of proapoptotic genes for P53, Bax, caspases-3, 8, and 9 at up to 6.18, 4.8, 9.8, 4.6, 11.3 fold-change, respectively, and downregualted the level of the antiapoptotic gene for Bcl-2 by 0.14-fold. Finally, a molecular docking study of the most active compound 8c highlighted a good binding affinity with Lys89 as the key amino acid for CDK-2 inhibition.


Asunto(s)
Antineoplásicos , Humanos , Oxindoles/farmacología , Oxindoles/química , Línea Celular Tumoral , Relación Estructura-Actividad , Roscovitina/farmacología , Simulación del Acoplamiento Molecular , Antineoplásicos/química , Proliferación Celular , Ensayos de Selección de Medicamentos Antitumorales , Estructura Molecular , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/química , Apoptosis
9.
ACS Appl Bio Mater ; 5(11): 5126-5139, 2022 11 21.
Artículo en Inglés | MEDLINE | ID: mdl-36259919

RESUMEN

Planar (2D) nanomaterials are garnering broad recognition in diverse scientific areas because of their intrinsic features. Herein, bulk graphitic carbon nitride (g-C3N4) was prepared from melamine, which was exfoliated to produce g-C3N4 nanosheets. The prepared g-C3N4 nanosheets were characterized by transmission electron microscopy (TEM), atomic force microscopy (AFM), photo luminescence (PL) spectroscopy, and dynamic light scattering (DLS). The stable dispersion of a g-C3N4 nanosheet was incorporated into a PVA/Gelatin matrix to explore its efficacy as a promising drug carrier. A remarkable 42% increase in tensile strength for 1% g-C3N4/PVA/Gelatin was attained compared with that of the PVA/Gelatin film. Thermal stability increased due to addition of g-C3N4 nanosheet in the PVA/Gelatin film, where the maximum thermal degradation temperature increased by 9.5 °C when the 1% nanosheet was added to the PVA/Gelatin film. Moreover, the g-C3N4 nanosheets and g-C3N4/PVA/Gelatin showed no cytotoxicity against HeLa and BHK-21 cells. To investigate the in vitro drug releasing efficacy, ciprofloxacin was incorporated into g-C3N4/PVA/Gelatin. Experimental results showed a 62% drug release within 120 min at physiological pH 7.4. The data was curve fitted by different kinetic models of drug release to understand the drug release mechanism. The experimental data was found to fit best with the Higuchi model and revealed the diffusion control mechanism of drug release. Additionally, antibacterial study confirmed the drug release potency from g-C3N4/PVA/Gelatin film on both Gram-positive and Gram-negative bacteria. The above-mentioned promising findings might lead to an opportunity of using g-C3N4 as a potential drug carrier.


Asunto(s)
Antibacterianos , Gelatina , Antibacterianos/farmacología , Gelatina/farmacología , Bacterias Gramnegativas , Bacterias Grampositivas , Portadores de Fármacos
10.
ACS Omega ; 7(25): 21465-21472, 2022 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-35785266

RESUMEN

Plinabulin (1, NPI2358), a vascular disrupting agent (VDA) molecule, is a synthetic analogue of the natural product phenylahistin (2, NPI 2350), which is isolated from Aspergillus ustus. Evaluation of the in vitro metabolic profile of VDA plinabulin using human liver microsomes (HLMs) and HepaRG Cells Cryopreserved is described. HLMs and HepaRG Cells Cryopreserved were prepared in-house and incubated with plinabulin according to published methodologies. The incubated mixtures were analyzed by liquid chromatography-ion trap mass spectrometry to identify possible metabolic products. The incubated plinabulin (1) revealed the presence of several peaks representing 19 tentative metabolites in HLMs and HepaRG Cells Cryopreserved in the presence of NADPH (nicotinamide adenine dinucleotide phosphate) and in the absence of NADPH-generating system, respectively. However, in NADPH absence, no metabolites and microsomes were generated for 1 in incubated HLMs, indicating a likely involvement of CYP450 enzymes in the metabolism. The metabolite structures, obtained from HLMs and HepaRG Cells Cryopreserved incubations, were elucidated by LC-MS/MS fragmentation study. Seventeen phase-I metabolites were proposed to be the results of isomerization, hydroxylation, hydration, and oxygenation of 1 in HLMs and two isomeric phase-II sulfate conjugate metabolites of 1 in HepaRG Cells Cryopreserved incubation.

11.
Sci Rep ; 12(1): 4757, 2022 03 19.
Artículo en Inglés | MEDLINE | ID: mdl-35306510

RESUMEN

Simvastatin (SV) is a hypolipidemic agent, and it is the 2nd most widely prescribed lipid-lowering drug. Here, the detection and characterization of SV and its metabolites was studied in selected organs/tissues (lung, liver, brain, heart and kidney) and biological samples (blood, urine and feces) of rats. MALDI Orbitrap MS was used as a high-resolution mass analyzer. 2,5-Dihydroxybenzoic acid (DHB) and 1,5-diaminonaphthalene (DAN) were used as matrices. Several sample loading methods onto the MALDI plate were attempted and dried droplet method was found to be superior. Two different cell disruption methods, pulverization and homogenization, were also evaluated for the optimum sensitivity in MALDI. Pulverization allowed the detection of more metabolites in all organs except the liver, where homogenization led to the detection of more metabolites. Altogether, 13 metabolites were detected, and one metabolite tentatively identified as a reduced product is being reported for the first time. SV and its metabolites were distributed to all the tissues studied except the brain. Overall, the results implied that the pulverized samples were more uniform and larger in surface area, resulting in their more efficient and complete extraction during sample preparation. As shown in the present study, MALDI Orbitrap MS is a useful tool to study drug and metabolite detection and characterization.


Asunto(s)
Hígado , Simvastatina , Animales , Heces/química , Riñón , Hígado/metabolismo , Ratas , Simvastatina/metabolismo , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos
12.
J Med Chem ; 65(4): 3388-3403, 2022 02 24.
Artículo en Inglés | MEDLINE | ID: mdl-35133171

RESUMEN

Histone acetylation is a prominent epigenetic modification linked to the memory loss symptoms associated with neurodegenerative disease. The use of existing histone deacetylase inhibitor (HDACi) drugs for treatment is precluded by their weak blood-brain barrier (BBB) permeability and undesirable toxicity. Here, we address these shortcomings by developing a new class of disulfide-based compounds, inspired by the scaffold of the FDA-approved HDACi romidepsin (FK288). Our findings indicate that our novel compound MJM-1 increases the overall level of histone 3 (H3) acetylation in a prostate cancer cell line. In mice, MJM-1 injected intraperitoneally (i.p.) crossed the BBB and could be detected in the hippocampus, a brain region that mediates memory. Consistent with this finding, we found that the post-training i.p. administration of MJM-1 enhanced hippocampus-dependent spatial memory consolidation in male mice. Therefore, MJM-1 represents a potential lead for further optimization as a therapeutic strategy for ameliorating cognitive deficits in aging and neurodegenerative diseases.


Asunto(s)
Encéfalo/metabolismo , Inhibidores de Histona Desacetilasas/síntesis química , Memoria Espacial/efectos de los fármacos , Animales , Línea Celular Tumoral , Inhibidores de Histona Desacetilasas/farmacocinética , Inhibidores de Histona Desacetilasas/farmacología , Ratones , Ratones Endogámicos BALB C
13.
J Enzyme Inhib Med Chem ; 36(1): 2055-2067, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34551654

RESUMEN

A series of quinazolin-4(3H)-one derivatives were synthesised and evaluated for their cytotoxicity against human Caucasian breast adenocarcinoma (MCF-7) and human ovarian carcinoma (A2780) cell lines. Cytotoxicity of the most tested compounds was 2- to 30-fold more than the positive control lapatinib (IC50 of 2j = 3.79 ± 0.96; 3j = 0.20 ± 0.02; and lapatinib = 5.9 ± 0.74) against MCF7 cell lines except two compounds (IC50 of 2 b = 15.72 ± 0.07 and 2e = 14.88 ± 0.99). On the other hand, cytotoxicity was 4 - 87 folds (IC50 of 3a = 3.00 ± 1.20; 3 g = 0.14 ± 0.03) more the positive control lapatinib (IC50 = 12.11 ± 1.03) against A2780 cell lines except compound 2e (IC50 = 16.43 ± 1.80). Among the synthesised quinazolin-4(3H)-one derivatives, potent cytotoxic 2f-j and 3f-j were investigated for molecular mechanism of action. Inhibitory activities of the compounds were tested against multiple tyrosine protein kinases (CDK2, HER2, EGFR and VEGFR2) enzymes. As expected, all the quinazolin-4(3H)-one derivatives were showed comparable inhibitory activity against those kinases tested, especially, compound 2i and 3i showed potent inhibitory activity against CDK2, HER2, EGFR tyrosine kinases. Therefore, molecular docking analysis for quinazolin-4(3H)-one derivatives 2i and 3i were performed, and it was revealed that compounds 2i and 3i act as ATP non-competitive type-II inhibitor against CDK2 kinase enzymes and ATP competitive type-I inhibitor against EGFR kinase enzymes. However, in case of HER2, compounds 2i act as ATP non-competitive type-II inhibitor and 3i act as ATP competitive type-I inhibitor. Docking results of known inhibitors were compared with synthesised compounds and found synthesised 2i and 3i are superior than the known inhibitors in case of interactions. In addition, in silico drug likeness properties of quinazolin-4(3H)-one derivatives showed better predicted ADME values than lapatinib.


Asunto(s)
Antineoplásicos/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Quinazolinonas/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Estructura Molecular , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/química , Proteínas Tirosina Quinasas/metabolismo , Quinazolinonas/síntesis química , Quinazolinonas/química , Relación Estructura-Actividad
14.
J Fluoresc ; 31(5): 1489-1502, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34287764

RESUMEN

Fluorescein (1), a known fluorescent tracer in microscopy with high photophysical properties, was esterified to have fluorescein ethyl ester (2) and O-ethyl-fluorescein ethyl ester (3) in excellent yields. All of them were investigated for the photophysical and electrochemical properties as potential organic semiconductor materials. Absorptions and emission spectra were taken in various solvents, compound 2 showed emission maxima at λmax = 545 and compound 3 showed λmax = 550 nm. Optical band gap energy (Eg) was calculated for 1-3 and the values were found in between 2.34 - 2.39 eV. Possibility of shifting emission maxima was studied in various pH (5-9) buffers, and finally the thermal stability was examined using differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Increasing of conjugation system of 2 and 3 were studied by HOMO and LUMO distributions of 1-3. Experimental results showed that compounds 2 and 3 have excellent photophysical and electrochemical properties hence can be used as excellent organic semiconductor materials.

15.
Mymensingh Med J ; 30(3): 855-859, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34226480

RESUMEN

Management of critically ill obstetric patients is a great challenge for the ICU team. The safety of both mother and fetus are of real concerns. Teamwork is essential for better outcome in obstetric patients in the ICU. A 26 years old female was admitted in Dhaka Medical College Hospital, Dhaka, Bangladesh on 18 August 2019 with 7 months pregnancy with brain tumor (later diagnosed as Gliosarcoma) and was managed surgically by left temporal craniotomy with excision of the tumor. The patient was shifted to the ICU due to repeated convulsions and need mechanical ventilator support. Later on, she was suffering from sepsis with pseudomonas in blood culture, grade IV pressure ulcer and electrolyte imbalance and needed tracheostomy for airway management. On 34th weeks of her pregnancy she developed antepartum hemorrhage with respiratory distress. Emergency LUCS was done and she delivered a LBW baby who was managed in NICU. Mother was managed in the ICU and later on both mother and child were discharge with good conditions. Multidisciplinary team work is vital for better management of critically ill obstetric patients.


Asunto(s)
Enfermedad Crítica , Complicaciones del Embarazo , Adulto , Bangladesh , Niño , Femenino , Humanos , Unidades de Cuidados Intensivos , Grupo de Atención al Paciente , Embarazo , Complicaciones del Embarazo/cirugía
16.
J Hazard Mater ; 401: 123277, 2021 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-33113710

RESUMEN

Multiple contaminants including heavy metals and phenolic compounds are normally co-exist in wastewater, which caused the treatment process is rather complicated. Herein, the synergistic photoredox of Cr(VI) and p-cresol (pC) by innovative fibrous silica zirconia (FSZr) photocatalyst was reported. The high surface area of FSZr comprised of microspheres with a bicontinuous concentric lamella structure morphology consisted of silica, while its core consisted of ZrO2 structure. The rearrangement of FSZr framework increased the crystallinity, formed Si-O-Zr bonds and narrowed the band gap of ZrO2 for enhanced of photoredox of Cr(VI) and pC. Compared to the reaction, the photoredox efficiency of FSZr for removing Cr(VI) and pC in simultaneous system was found to be 96 % and 59 %, respectively which are higher than that in its single system owing to the efficient electron-hole charge separation. Phenolic compound with high degree of electron donating group gave beneficial effect to photoreduction of Cr(VI). Consequently, a proposed mechanism involving multi-photoredox pathway were proposed based on photoredox reaction and scavengers studies. FSZr sustained the simultaneous photoredox activities after five runs demonstrating its possibility to be use in the wastewater treatment of various pollutants.

17.
Molecules ; 25(24)2020 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-33322201

RESUMEN

Galeon, a natural cyclic-diarylheptanoid (CDH), which was first isolated from Myrica gale L., is known to have potent cytotoxicity against A549 cell lines, anti-tubercular activity against Mycobacterium tuberculosis H37Rv, chemo-preventive potential, and moderate topoisomerase inhibitory activity. Here, in silico metabolism and toxicity prediction of galeon by CYP450, in vitro metabolic profiling study in rat liver microsomes (RLMs), and molecular interactions of galeon-CYP450 isoforms were performed. An in silico metabolic prediction study showed demethyl and mono-hydroxy galeon were the metabolites with the highest predictability. Among the predicted metabolites, mono-hydroxy galeon was found to have plausible toxicities such as skin sensitization, thyroid toxicity, chromosome damage, and carcinogenicity. An in vitro metabolism study of galeon, incubated in RLMs, revealed eighteen Phase-I metabolites, nine methoxylamine, and three glutathione conjugates. Identification of possible metabolites and confirmation of their structures were carried out using ion-trap tandem mass spectrometry. In silico docking analysis of galeon demonstrated significant interactions with active site residues of almost all CYP450 isoforms.


Asunto(s)
Sistema Enzimático del Citocromo P-450/química , Sistema Enzimático del Citocromo P-450/metabolismo , Diarilheptanoides/química , Diarilheptanoides/metabolismo , Microsomas Hepáticos/metabolismo , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Animales , Sitios de Unión , Isoenzimas , Conformación Molecular , Estructura Molecular , Unión Proteica , Ratas , Relación Estructura-Actividad
18.
PLoS One ; 15(12): e0239918, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33270656

RESUMEN

This study describes, for the first time, the experimental and computational investigations for evaluation of kolliphor RH 40 as a fluorescence enhancer surfactant in development of a spectrofluorimetric method for determination of lapatinib (LAP), a tyrosine kinase-inhibitor drug approved for targeted therapy of breast cancer. The investigations involved the ability of kolliphor RH 40 to form micelles with LAP and its enhancing effect on the weak native fluorescence of LAP at 420 nm after its excitation at 292 nm. Different variables were experimentally investigated: types of organized media, diluting solvent, buffer type and its pH value. The optimum values of the most influencing variables on the interaction of kolliphor RH 40 with LAP were refined by the computational response surface methodology (RSM). Under the optimized conditions, it was found that kolliphor RH 40 forms micelles with LAP, and its fluorescence enhancing ability was higher than other surfactants tested by ~ 10-folds. This micellar-enhanced effect of kolliphor RH 40 was employed in the development of a new sensitive spectrofluorimetric method for the accurate determination of LAP. The method was validated according to the guidelines of the International Conference on Harmonization (ICH) for validation of analytical procedures. The relative fluorescence intensity (RFI) was in excellent linear relationship (correlation coefficient was 0.998) with the LAP concentrations in the range of 50-1000 ng/mL. The method limit of detection (LOD) was 27.31 ng/mL and its accuracy was ≥ 99.82%. The method was successfully applied to the determination of LAP in its pharmaceutical tablets, tablets dissolution testing and content uniformity. The method application was extended to the determination of LAP in urine samples with an accuracy of 99.82 ± 3.45%. The method is considered as an eco-friendly green approach and more efficient alternative method to the existing analytical methodologies for determination of LAP.


Asunto(s)
Lapatinib/análisis , Espectrometría de Fluorescencia/métodos , Comprimidos/química , Humanos , Micelas , Reproducibilidad de los Resultados
19.
Molecules ; 25(19)2020 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-32992673

RESUMEN

Isatin derivatives potentially act on various biological targets. In this article, a series of novel isatin-hydrazones were synthesized in excellent yields. Their cytotoxicity was tested against human breast adenocarcinoma (MCF7) and human ovary adenocarcinoma (A2780) cell lines using MTT assay. Compounds 4j (IC50 = 1.51 ± 0.09 µM) and 4k (IC50 = 3.56 ± 0.31) showed excellent activity against MCF7, whereas compound 4e showed considerable cytotoxicity against both tested cell lines, MCF7 (IC50 = 5.46 ± 0.71 µM) and A2780 (IC50 = 18.96± 2.52 µM), respectively. Structure-activity relationships (SARs) revealed that, halogen substituents at 2,6-position of the C-ring of isatin-hydrazones are the most potent derivatives. In-silico absorption, distribution, metabolism and excretion (ADME) results demonstrated recommended drug likeness properties. Compounds 4j (IC50 = 0.245 µM) and 4k (IC50 = 0.300 µM) exhibited good inhibitory activity against the cell cycle regulator CDK2 protein kinase compared to imatinib (IC50 = 0.131 µM). A molecular docking study of 4j and 4k confirmed both compounds as type II ATP competitive inhibitors that made interactions with ATP binding pocket residues, as well as lacking interactions with active state DFG motif residues.


Asunto(s)
Neoplasias de la Mama/enzimología , Quinasa 2 Dependiente de la Ciclina , Citotoxinas , Hidrazonas , Isatina , Simulación del Acoplamiento Molecular , Proteínas de Neoplasias , Neoplasias Ováricas/enzimología , Inhibidores de Proteínas Quinasas , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Quinasa 2 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 2 Dependiente de la Ciclina/química , Citotoxinas/química , Citotoxinas/farmacología , Femenino , Humanos , Hidrazonas/química , Hidrazonas/farmacología , Isatina/química , Isatina/farmacología , Células MCF-7 , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/química , Proteínas de Neoplasias/metabolismo , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/farmacología
20.
Mymensingh Med J ; 29(2): 488-494, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32506111

RESUMEN

Since the first recorded case of SARS-CoV-2 in Bangladesh on 8th March 2020, COVID-19 has spread widely through different regions of the country, resulting in a necessity to re-evaluate the delivery of cardiovascular services, particularly procedures pertaining to interventional cardiology in resource-limited settings. Given its robust capacity for human-to-human transmission and potential of being a nosocomial source of infection, the disease has specific implications on healthcare systems and health care professionals faced with performing essential cardiac procedures in patients with a suspected or confirmed diagnosis of COVID-19. The limited resources in terms of cardiac catheterization laboratories that can be designated to treat only COVID positive patients are further compounded by the additional challenges of unavailability of widespread rapid testing on-site at tertiary cardiac hospitals in Bangladesh. This document prepared for our nation by the Bangladesh Society of Cardiovascular Interventions (BSCI) is intended to serve as a clinical practice guideline for cardiovascular health care professionals, with a focus on modifying standard practice of care during the COVID-19 pandemic, in order to ensure continuation of adequate and timely treatment of cardiovascular emergencies avoiding hospital-based transmission of SARS-COV-2 among healthcare professionals and the patients. This is an evolving document based on currently available global data and is tailored to healthcare systems in Bangladesh with particular focus on, but not limited to, invasive cardiology facilities (cardiac catheterization, electrophysiology & pacing labs). This guideline is limited to the provision of cardiovascular care, and it is expected that specific targeted pharmaco-therapeutics against SARS-CoV-2 be prescribed as stipulated by the National Guidelines on Clinical Management of Corona virus Disease 2019 (COVID-19) published by the Director General of Health Services, Ministry of Health and Family Welfare of Bangladesh.


Asunto(s)
Enfermedades Cardiovasculares , Procedimientos Quirúrgicos Cardiovasculares , Infecciones por Coronavirus , Pandemias , Neumonía Viral , Bangladesh , Betacoronavirus , COVID-19 , Enfermedades Cardiovasculares/terapia , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/epidemiología , Humanos , Neumonía Viral/complicaciones , Neumonía Viral/epidemiología , SARS-CoV-2
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