An electrochemical sensor based on copper-based metal–organic framework-reduced graphene oxide composites for determination of 2,4-dichlorophenol in water

In the present work, we reported the fabrication of a novel electrochemical sensing platform to detect 2,4-dichlorophenol (2,4-DCP) by using a copper benzene-1,3,5-tricarboxylate–graphene oxide (Cu–BTC/GO) composite. The sensor was prepared by drop-casting Cu–BTC/GO suspension onto the electrode surface followed by electrochemical reduction, leading to the generation of an electrochemically reduced graphene oxide network (ErGO). By combining the large specific area of the Cu–BTC matrix with the electrical percolation from the graphene network, the number of accessible reaction sites was strongly increased, which consequently improved the detection performance. The electrochemical characteristics of the composite were revealed by cyclic voltammetry and electrochemical impedance spectroscopy. For the detection of 2,4-DCP, differential pulse voltammetry was used to emphasize the faradaic reaction related to the oxidation of the analyte. The results displayed a low detection limit (83 × 10⁻⁹ M) and a linear range from 1.5 × 10⁻⁶ M to 24 × 10⁻⁶ M alongside high reproducibility (RSD = 2.5% for eight independent sensors) and good stability. Importantly, the prepared sensors were sufficiently selective against interference from other pollutants in the same electrochemical window. Notably, the presented sensors have already proven their ability in detecting 2,4-DCP in real field samples with high accuracy (recovery range = 97.17–104.15%).

In the present work, we reported the fabrication of a novel electrochemical sensing platform to detect 2,4-dichlorophenol (2,4-DCP) by using a copper benzene-1,3,5-tricarboxylate–graphene oxide (Cu–BTC/GO) composite.     

Pyridine appended 2-hydrazinylthiazole derivatives: design,synthesis, in vitro and in silico antimycobacterial studies

An array of pyridine appended 2-hydrazinylthiazole derivatives has been synthesized to discover novel chemotherapeutic agents for Mycobacterium tuberculosis (Mtb). The drug-likeness of pyridine appended 2-hydrazinylthiazole derivatives was validated using the Lipinski and Veber rules. The designed thiazole molecules have been synthesized through Hantzsch thiazole methodologies. The in vitro antimycobacterial studies have been conducted using Luciferase reporter phage (LRP) assay. Out of thirty pyridine appended 2-hydrazinylthiazole derivatives, the compounds 2b, 3b, 5b, and 8b have exhibited good antimycobacterial activity against Mtb, an H37Rv strain with the minimum inhibitory concentration in the range of 6.40–7.14 μM. In addition, in vitro cytotoxicity of active molecules has been observed against Human Embryonic Kidney Cell lines (HEK293t) using MTT assay. The compounds 3b and 8b are nontoxic and their cell viability is 87% and 96.71% respectively. The in silico analyses of the pyridine appended 2-hydrazinylthiazole derivatives have been studied to find the mode of binding of the active compounds with KasA protein of Mtb. The active compounds showed a strong binding score (−5.27 to −6.23 kcal mol⁻¹).

Thirty novel pyridine-appended 2-hydrazinylthiazole derivatives have been synthesized and tested for their antimycobacterial activity against Mictrobactrium tuberculosis, H37Rv strain.     

Quantification of salicylate in serum by use of salicylate hydroxylase

In this enzymatic method for salicylate in serum, Pseudomonas salicylate hydroxylase (EC 1.14.13.1) is used. This stable enzyme catalyzes the stoichiometric, unidirectional conversion of salicylate and NAD(P)H to catechol and NAD(P)+ in the presence of molecular oxygen. The concentration of salicylate in a clinical sample is determined by measuring the delta A at 340 nm as compared with a standard. This new method is rapid, highly specific, requires 40 microL or less of sample, and we saw no interference by any of 61 commonly used drugs. Lipemic, icteric, or hemolyzed samples can be used. Furthermore, this method does not involve extraction, deproteinization, or derivatization. Results are precise and agree well with those obtained by the Trinder test.     

Synthesis,crystal structure and in silico studies of novel 2,4-dimethoxy-tetrahydropyrimido[4,5-b]quinolin-6(7H)-ones

Herein, acetic acid mediated multicomponent synthesis of novel 2,4-dimethoxy-tetrahydropyrimido[4,5-b]quinolin-6(7H)-one (2,4-dimethoxy-THPQs) was reported. Single-crystal XRD analysis of four newly developed crystals of 2,4-dimethoxy-THPQs and their DFT study were also reported. The structure of all molecules was optimized using DFT B3LYP/6-31G(d) level and compared with the corresponding single-crystal XRD data. As a result, the theoretical and experimental geometrical parameters (bond lengths and bond angles) were found to be in good agreement. Frontier molecular orbital (FMO) and molecule electrostatic potential (MEP) analyses were used to investigate the physicochemical properties and relative reactivity of 2,4-dimethoxy-THPQs. The formation of strong C–H⋯O and N–H⋯O interaction was investigated by Hirshfeld analysis. Furthermore, electronic charge density concentration in 2,4-dimethoxy-THPQs was analysed by the Mulliken atomic charges which helps to predict the ability of 2,4-dimethoxy-THPQs to bind in the receptor. The molecular docking of the crystal structure of 2,4-dimethoxy-THPQs in the main protease (M^pro) of SARS-CoV-2 suggested that all four 2,4-dimethoxy-THPQs efficiently docked in M^pro. Furthermore, 2,4-dimethoxy-THPQs with a 3-chloro substitution in the phenyl ring have the highest binding affinity because of the additional formation of halogen bonds and highest dipole moment.

Single-crystal XRD analysis of 2,4-dimethoxy THPQs and their relative reactivity with properties were investigated using DFT calculation. Molecular docking studies show they effectively docked with main protease of SARS-CoV-2.     

In silico and in vitro design of cordycepin encapsulation in liposomes for colon cancer treatment

Cordycepin or 3′-deoxyadenosine is an interesting anti-cancer drug candidate that is found in abundance in the fungus Cordyceps militaris. It inhibits cellular growth of many cancers including lung carcinoma, melanoma, bladder cancer, and colon cancer by inducing apoptosis, anti-proliferation, anti-metastasis and by arresting the cell cycle. Cordycepin has, however, poor stability and low solubility in water, resulting in loss of its bioactivity. Liposomes can be used to overcome these obstacles. Our aim is to improve cordycepin''s anti-colon cancer activity by liposome encapsulation. Cordycepin-encapsulated liposomes were designed and fabricated based on a combination of theoretical and experimental studies. Molecular dynamics (MD) simulations and free energy calculations suggest that phosphatidylcholine (PC) lipid environment is favorable for cordycepin adsorption. Cordycepin passively permeates into PC lipid bilayers without membrane damage and strongly binds to the lipids'' polar groups by flipping its deoxyribose sugar toward the bilayer center. Our fabricated liposomes containing 10 : 1 molar ratio of egg yolk PC : cholesterol showed encapsulation efficiency (%EE) of 99% using microfluidic hydrodynamic focusing (MHF) methods. In our in vitro study using the HT-29 colon cancer cell line, cordycepin was able to inhibit growth by induction of apoptosis. Cell viability was significantly decreased below 50% at 125 μg mL⁻¹ dosage after 48 h treatment with non-encapsulated and encapsulated cordycepin. Importantly, encapsulation provided (1) a 2-fold improvement in the inhibition of cancer cell growth at 125 μg mL⁻¹ dosage and (2) 4-fold increase in release time. These in silico and in vitro studies indicate that cordycepin-encapsulated liposomes could be a potent drug candidate for colon cancer therapy.

Cordycepin-encapsulated liposomes could be a potent drug candidate for cancer therapy.     

Uracil derivatives as HIV-1 capsid protein inhibitors: design,in silico,in vitro and cytotoxicity studies

A series of novel uracil derivatives such as bispyrimidine dione and tetrapyrimidine dione derivatives were designed based on the existing four-point pharmacophore model as effective HIV capsid protein inhibitors. The compounds were initially docked with an HIV capsid protein monomer to rationalize the ideas of design and to find the potential binding modes. The successful design and computational studies led to the synthesis of bispyrimidine dione and tetrapyrimidine dione derivatives from uracil and aromatic aldehydes in the presence of HCl using novel methodology. The in vitro evaluation in HIV p24 assay revealed five potential uracil derivatives with IC₅₀ values ranging from 191.5 μg ml⁻¹ to 62.5 μg ml⁻¹. The meta-chloro substituted uracil compound 9a showed promising activity with an IC₅₀ value of 62.5 μg ml⁻¹ which is well correlated with the computational studies. As expected, all the active compounds were noncytotoxic in BA/F3 and Mo7e cell lines highlighting the thoughtful design. The structure activity relationship indicates the position priority and lower log P values as the possible cause of inhibitory potential of the uracil compounds.

The paper describes the design, synthesis, computational and biological validation of a series of novel uracil derivatives as effective HIV capsid protein inhibitors.     

Inhibition of prolyl hydroxylase activity in the aorta of rats by propranolol in vitro

The enzyme of prolyl hydroxylase was prepared from the rat aorta. The prolyl hydroxylase activity was measured by the tritium release assay in vitro. Propranolol at concentrations of 3 X 10(-6)M, 10(-5)M inhibited the prolyl hydroxylase activity by 20.6%, 69.8% and 93.7% of control activity, respectively, when the reaction mixtures were incubated for 30 min. It is suggested that propranolol may exert some influence on the collagen biosynthesis of the blood vessels.     

Induction of aryl hydrocarbon hydroxylase in human pulmonary alveolar macrophages by cigarette smoking

Pulmonary alveolar macrophages were obtained from healthy volunteers by saline pulmonary lavage, and aryl hydrocarbon hydroxylase was measured in the cells. Enzyme activity was low in cells from five nonsmokers with a mean of 0.008±0.004 U/10⁶ cells. Cells obtained from nine cigarette smokers contained higher enzyme levels, with a mean of 0.095±0.024 U/10⁶ cells. A former cigarette smoker was lavaged on five occasions. Enzyme activity during two lavages 4 mo apart were 0.010 and 0.009 U/10⁶ cells, respectively. 1 wk after smoking was resumed, the enzyme activity rose slightly to 0.013, and reached 0.041 U/10⁶ cells by 1 mo. Upon cessation of smoking, the enzyme activity returned to control levels by the next lavage, 2 mo later. These data indicate that aryl hydrocarbon hydroxylase may be induced in pulmonary alveolar macrophages of subjects chronically exposed to cigarette smoke.     

Antiulcer secondary metabolites from Elaeocarpus grandis,family Elaeocarpaceae,supported by in silico studies

Elaeocarpus grandis has a very potent analgesic effect, especially to a δ-opioid receptor, but its antiulcer activity has not yet been validated. Therefore, the present study was carried out to evaluate the antiulcer potential of the total methanolic extract and its derived fractions of the aerial parts of the plant using an indomethacin-induced gastric ulcer method. One new compound, grandisine H (1), and five known compounds, P-methoxy benzaldehyde, methyl gallate, kaempferol, quercetin and heterophyllin A (2–6), were isolated from the ethyl acetate fraction, which was the most potent one with an ulcer index value of 5 ± 1.95 (mm) ** (*P < 0.05, **P < 0.01) and a preventive index of 92.9%, following a bioassay-guided fractionation. The isolated compounds were subjected to a molecular docking study in an attempt to explain their significant antiulcer potential, and the results revealed that kaempferol and quercetin bind to the active site of the M3 receptor with a strong binding affinity via strong hydrogen bonds of −6.081 kcal mol⁻¹ and −6.013 kcal mol⁻¹, respectively. Also, quercetin and heterophyllin A showed a binding affinity with the gastric proton pump receptor and a strong hydrogen bond interaction with the amino acid active sites in the case of an H₂-modeled receptor. These results clarify the effectiveness and importance of the ethyl acetate fraction as a natural anti-ulcer remedy.

Elaeocarpus grandis has a very potent analgesic effect, especially to a δ-opioid receptor, but its antiulcer activity has not yet been validated.     

Reduction of globotriaosylceramide in Fabry disease mice by substrate deprivation

We used a potent inhibitor of glucosylceramide synthase to test whether substrate deprivation could lower globotriaosylceramide levels in alpha-galactosidase A (alpha-gal A) knockout mice, a model of Fabry disease. C57BL/6 mice treated twice daily for 3 days with D-threo-1-ethylendioxyphenyl-2-palmitoylamino-3-pyrrolidi no-propanol (D-t-EtDO-P4) showed a concentration-dependent decrement in glucosylceramide levels in kidney, liver, and spleen. A single intraperitoneal injection of D-t-EtDO-P4 resulted in a 55% reduction in renal glucosylceramide, consistent with rapid renal glucosylceramide metabolism. A concentration-dependent decrement in renal and hepatic globotriaosylceramide levels was observed in alpha-Gal A(-) males treated for 4 weeks with D-t-EtDO-P4. When 8-week-old alpha-Gal A(-) males were treated for 8 weeks with 10 mg/kg twice daily, renal globotriaosylceramide fell to below starting levels, consistent with an alpha-galactosidase A-independent salvage pathway for globotriaosylceramide degradation. Complications observed with another glucosylceramide synthase inhibitor, N-butyldeoxynojirimycin, including weight loss and acellularity of lymphatic organs, were not observed with D-t-EtDO-P4. These data suggest that Fabry disease may be amenable to substrate deprivation therapy.     

小鼠垂体瘤细胞内表达人酪氨酸羟化酶诱导产生内源性多巴胺的细胞毒性作用

目的:观察人酪氨酸羟化酶转染小鼠垂体瘤细胞产生的内源性多巴胺对细胞生存能力的影响,同时观察转染细胞对体外实验中证实可诱导多巴胺能神经元凋亡具有细胞毒性作用的选择性植物源鱼藤酮敏感性的变化(多巴胺含量越多,对鱼藤酮越敏感,鱼藤酮处理后死亡细胞越多),进一步证实多巴胺的毒性作用。方法:实验于2002-06/2003-06在美国匹兹堡大学神经生物实验室进行。将野生型和变异型人酪氨酸羟化酶表达质粒hTH-wt/pcDNA3.1和hTH-RREE/pcDNA3.1(Arg37Glu及Arg38Glu,具有持续活性)转染小鼠垂体瘤细胞细胞。将细胞随机分为hTH-wt/pcDNA3.1转染组和hTH-RREE/pcDNA3.1转染组及用相同转染方法处理,但不加入表达质粒的对照组。用Westernblot和高效液相色谱法检测人酪氨酸羟化酶、内源性多巴胺的含量;用四唑盐比色法检测转染细胞生存率;用新型细胞核萤光染料,不能透过细胞膜的SYTOXgreen试验检测死亡细胞数量及对鱼藤酮的敏感性;再用半胱氨酸天冬氨酸蛋白酶3免疫染色结合Hoechst核染色检测转染细胞凋亡情况。结果:①细胞生存率:小鼠垂体瘤细胞转染3d后,hTH-wt/pcD-NA3.1和hTH-RREE/pcDNA3.转染组分别是对照组的80.3%和81.4%(P<0.05),但两组间无差异(P>0.05)。②细胞死亡率:hTH-wt/pcDNA3.1转染细胞经鱼藤酮处理后,是未经鱼藤酮处理的1.57倍(P<0.05),hTH-RREE/pcDNA3.1转染细胞用鱼藤酮处理后,是未经鱼藤酮处理的1.88倍,但两组间无差异(P>0.05)。③凋亡细胞比率:转染hTH-wt/pcDNA3.1和hTH-RREE/pcDNA3.1后,分别是对照组的4.84和4.24倍(P<0.05)。④多巴胺、二羟苯乙酸含量:转染hTH-RREE的细胞多巴胺含量是转染hTH-wt者的4.5倍(P=0.027),但两种细胞内的二羟苯乙酸含量无明显差异。结论:小鼠垂体瘤细胞转染人酪氨酸羟化酶后可产生内源性多巴胺,可导致细胞死亡,可增加小鼠垂体瘤细胞对鱼藤酮的敏感性,同时产生的细胞凋亡参与转染细胞的死亡过程。     

小鼠垂体瘤细胞内表达人酪氨酸羟化酶诱导产生内源性多巴胺的细胞毒性作用

目的：观察人酪氨酸羟化酶转染小鼠垂体瘤细胞产生的内源性多巴胺对细胞生存能力的影响，同时观察转染细胞对体外实验中证实可诱导多巴胺能神经元凋亡具有细胞毒性作用的选择性植物源鱼藤酮敏感性的变化（多巴胺含量越多，对鱼藤酮越敏感，鱼藤酮处理后死亡细胞越多），进一步证实多巴胺的毒性作用。方法：实验于2002-06／2003-06在美国匹兹堡大学神经生物实验室进行。将野生型和变异型人酪氨酸羟化酶表达质粒hTH-wt／pcDNA3.1和hTH-RREE／pcDNA3．1（Arg37Glu及Arg38Glu，具有持续活性）转染小鼠垂体瘤细胞细胞。将细胞随机分为hTH-wt／pcDNA3．1转染组和hTH-RREE／pcDNA3．1转染组及用相同转染方法处理，但不加入表达质粒的对照组。用Western blot和高效液相色谱法检测人酪氨酸羟化酶、内源性多巴胺的含量；用四唑盐比色法检测转染细胞生存率；用新型细胞核萤光染料，不能透过细胞膜的SYTOX green试验检测死亡细胞数量及对鱼藤酮的敏感性；再用半胱氨酸天冬氨酸蛋白酶3免疫染色结合Hoechst核染色检测转染细胞凋亡情况。结果；①细胞生存率：小鼠垂体瘤细胞转染3d后，hTH-wt／pcD-NA3.1和hTH-RREE／pcDNA3．转染组分别是对照组的80.3％和81．4％（P〈0．05），但两组间无差异（P〉0．05）。②细胞死亡率：hTH-wt／pcDNA3．1转染细胞经鱼藤酮处理后，是未经鱼藤酮处理的1．57倍（P〈0．05），hTH-RREE／pcDNA3．1转染细胞用鱼藤酮处理后，是未经鱼藤酮处理的1．88倍，但两组间无差异（P〉0．05）。④凋亡细胞比率：转染hTH-wt／pcDNA3．1和hTH-RREE／pcDNA3．1后，分别是对照组的4．84和4．24倍（P〈0．05）。④多巴胺、二羟苯乙酸含量：转染hTH-RREE的细胞多巴胺含量是转染hTH-wt者的4．5倍（P=0．027），但两种细胞内的二羟苯乙酸含量无明显差异。结论：小鼠垂体瘤细胞转染人酪氨酸羟化酶后可产生内源性多巴胺，可导致细胞死亡，可增加小鼠垂体瘤细胞对鱼藤酮的敏感性，同时产生的细胞凋亡参与转染细胞的死亡过程。     

Design,synthesis, in silico docking,ADMET and anticancer evaluations of thiazolidine-2,4-diones bearing heterocyclic rings as dual VEGFR-2/EGFRT790M tyrosine kinase inhibitors

Fourteen recent thiazolidine-2,4-diones bearing furan and/or thiophene heterocyclic rings have been designed, synthesized and assessed for their anticancer activities against four human tumor cell lines HepG2, A549, MCF-7 and HCT-116 targeting both VEGFR-2 and EGFR tyrosine kinases. Molecular design was carried out to investigate the binding mode of the proposed compounds with VEGFR-2 and EGFR receptors. HepG2 was the most susceptible cell line to the influence of our derivatives. Compounds 5g and 4g revealed the highest activities against HepG2 (IC₅₀ = 3.86 and 6.22 μM), A549 (IC₅₀ = 7.55 and 12.92 μM), MCF-7 (IC₅₀ = 10.65 and 10.66 μM) and HCT116 (IC₅₀ = 9.04 and 11.17 μM) tumor cell lines. Sorafenib (IC₅₀ = 4.00, 4.04, 5.58 and 5.05 μM) and elotinib (IC₅₀ = 7.73, 5.49, 8.20 and 13.91 μM) were used as reference standards. Furthermore, the most active cytotoxic compounds 4d, 4e, 4f, 4g, 5d, 5e, 5f and 5g were selected to assess their VEGFR-2 inhibitory effects. Derivatives 5g, 4g and 4f were observed to be the highest effective derivatives that inhibited VEGFR-2 at the submicromolar level (IC₅₀ = 0.080, 0.083 and 0.095 μM respectively) in comparison to sorafenib (IC₅₀ = 0.084 μM). As well, compounds 4d, 4e, 4f, 4g, 5d, 5e, 5f and 5g were additionally assessed for their inhibitory activities against mutant EGFR^T790M. Compounds 5g and 4g could interfere with the EGFR^T790M activity exhibiting stronger activities than elotinib with IC₅₀ = 0.14 and 0.23 μM respectively. Finally, our derivatives 4g, 5f and 5g showed a good in silico calculated ADMET profile. The obtained results showed that our compounds could be useful as a template for future design, optimization, adaptation and investigation to produce more potent and selective dual VEGFR-2/EGFR^T790M inhibitors with higher anticancer activity.

Fourteen recent thiazolidine-2,4-diones bearing furan and/or thiophene heterocyclic rings have been designed, synthesized and assessed for their anticancer activities against four human tumor cell lines HepG2, A549, MCF-7 and HCT-116 targeting both VEGFR-2 and EGFR tyrosine kinases.     

Ion Torrent PGM~(TM)测序仪检测苯丙酮尿症患儿苯丙氨酸羟化酶基因突变

目的评价Ion Torrent PGMTM测序仪检测苯丙酮尿症(PKU)患儿苯丙氨酸羟化酶基因(PAH)突变的可行性。方法提取15例确诊为经典型PKU的患儿及其父母外周血DNA,对PAH全部外显子及外显子-内含子交界区进行PCR反应,用Ion Torrent PGMTM测序仪测序,再对检出突变的样本进行Sanger法验证。结果 Ion Torrent PGMTM平均覆盖深度为1 465倍,平均覆盖率为99.3%;共检出29个突变位点,分属17种突变,其中p.P292L为新发突变,所有检测结果均与Sanger法相一致。结论用Ion Torrent PGMTM测序仪可快速简便检测PKU患儿PAH基因突变。     

The anti-Alzheimer potential of Tamarindus indica: an in vivo investigation supported by in vitro and in silico approaches

Tamarindus indica Linn. (Tamarind, F. Fabaceae) is one of the most widely consumed fruits in the world. A crude extract and different fractions of T. indica (using n-hexane, dichloromethane, ethyl acetate, and n-butanol) were evaluated in vitro with respect to their DPPH scavenging and AchE inhibition activities. The results showed that the dichloromethane and ethyl acetate fractions showed the highest antioxidant activities, with 84.78 and 86.96% DPPH scavenging at 0.10 μg mL⁻¹. The n-hexane, dichloromethane, and ethyl acetate fractions inhibited AchE activity in a dose-dependent manner, and the n-hexane fraction showed the highest inhibition at 20 μg mL⁻¹. The results were confirmed by using n-hexane, dichloromethane, and ethyl acetate fractions in vivo to regress the neurodegenerative features of Alzheimer''s dementia in an aluminum-intoxicated rat model. Phytochemical investigations of those three fractions afforded two new diphenyl ether derivative compounds 1–2, along with five known ones (3–7). The structures of the isolated compounds were confirmed via 1D and 2D NMR and HRESIMS analyses. The isolated compounds were subjected to extensive in silico-based investigations to putatively highlight the most probable compounds responsible for the anti-Alzheimer activity of T. indica. Inverse docking studies followed by molecular dynamics simulation (MDS) and binding free energy (ΔG) investigations suggested that both compounds 1 and 2 could be promising AchE inhibitors. The results presented in this study may provide potential dietary supplements for the management of Alzheimer''s disease.

In vivo anti-Alzheimer''s and antioxidant potential of Tamarindus indica supported by molecular docking.     

New quinoxaline-based VEGFR-2 inhibitors: design,synthesis, and antiproliferative evaluation with in silico docking,ADMET, toxicity,and DFT studies

A new series of 3-methylquinoxaline-based derivatives having the same essential pharmacophoric features as VEGFR-2 inhibitors have been synthesized and evaluated for their antiproliferative activities against two human cancer cell lines, MCF-7 and HepG-2. Compounds 15b and 17b demonstrated a significant antiproliferative effect with IC₅₀ ranging from 2.3 to 5.8 μM. An enzymatic assay was carried out for all the tested candidates against VEGFR-2. Compound 17b was the most potent VEGFR-2 inhibitor (IC₅₀ = 2.7 nM). Mechanistic investigation including cell cycle arrest and apoptosis was performed for compound 17b against HepG-2 cells, and the results revealed that 17b induced cell apoptosis and arrested cell cycle in the G2/M phase. Moreover, apoptosis analyses were conducted for compound 17b to evaluate its apoptotic potential. The results showed upregulation in caspase-3 and caspase-9 levels, and improving the Bax/Bcl-2 ratio by more than 10-fold. Docking studies were performed to determine the possible interaction with the VEGFR-2 active site. Further docking studies were carried out for compound 17b against cytochrome P450 to present such compounds as non-inhibitors. In silico ADMET, toxicity, and physico-chemical properties revealed that most of the synthesized members have acceptable values of drug-likeness. Finally, DFT studies were carried out to calculate the thermodynamic, molecular orbital and electrostatic potential properties.

A new series of 3-methylquinoxaline-based derivatives having the same pharmacophoric features of VEGFR-2 inhibitors have been synthesized and evaluated for their antiproliferative activities against MCF-7 and HepG-2 cells.     

Efficient corrosion inhibition by sugarcane purple rind extract for carbon steel in HCl solution: mechanism analyses by experimental and in silico insights

Sugarcane purple rind ethanolic extract (SPRE) was evaluated as an efficient corrosion inhibitor for carbon steel (C-steel) in 1 M HCl solution. Dynamic weight loss, potentiodynamic polarization, electrochemical impedance spectroscopy (EIS) and frequency modulation (EFM) measurements were employed to evaluate the anticorrosive efficiency of SPRE, which was further validated by morphological and wettability analyses. The results of the weight loss tests showed that the inhibition efficiency (η_w) for C-steel in HCl solution increased with an increase in the concentration of SPRE. An increase in temperature moderately impaired the anticorrosive efficacy of SPRE. The maximum η_w of 96.2% was attained for C-steel in the inhibition system with 800 mg L⁻¹ SPRE at 298 K. The polarization curves indicated that SPRE simultaneously suppressed the anodic and cathodic reactions for C-steel in HCl solution, which can be categorized as a mixed-type corrosion inhibitor with a predominant anodic effect. The corrosion current density (i_corr-P) was monotonously reduced with an increase in the concentration of SPRE. The charge transfer resistance (R_ct) was enhanced for C-steel in the inhibition solution with a restrained capacitive property due to the adsorption of SPRE. A high temperature caused partial desorption of SPRE on the C-steel surface and a slight increase in i_corr-P and decrease in R_ct. However, SPRE still fully maintained its morphology and wettability at 328 K. The electrochemical kinetics of C-steel in HCl solution without and with SPRE was also supported by EFM spectra. The adsorption of SPRE conformed to the Langmuir isotherm and increased the corrosion activation energy of C-steel. Complementing the experimental observations, calculations based on density functional theory indicated that the hydroxyl-substituted pyran moiety on the carthamin (CTM) and anthocyanin (ATC) constituents in SPRE hardly contributed to its reactive activity due to their adsorption processes. Therefore, CTM and ATC exhibited imperfect parallel adsorption on the Fe (100) plane according to the molecular dynamics simulation, while anthoxanthin (ATA) and catechinic acid (CCA) constituents exhibited a flat orientation on the iron surface.

The anticorrosive mechanism of extracted components from sugarcane purple rind for carbon steel in HCl solution is clarified by weight loss, electrochemical and theoretical (novel DFT calculation and molecular dynamics simulation) analyses.