The current mechanistic study was conducted to explore the effects of increased lipophilicity of binuclear silver(I)-NHC complexes on cytotoxicity. Two new silver(I)-N-Heterocyclic Carbene (NHC) complexes (3 and 4), having lypophilic terminal alkyl chains (Octyl and Decyl), were derived from meta-xylyl linked bis-benzimidazolium salts (1 and 2). Each of the synthesized compounds was characterized by microanalysis and spectroscopic techniques. The complexes were tested for their cytotoxicity against a panel of human cancer c as well normal cell lines using MTT assay. Based on MTT assay results, complex 4 was found to be selectively toxic towards human colorectal carcinoma cell line (HCT 116). Complex 4 was further studied in detail to explore the mechanism of cell death and findings of the study revealed that complex 4 has promising pro-apoptotic and anti-metastatic activities against HCT 116 cells. Furthermore, it showed pronounced cytostatic effects in HCT 116 multicellular spheroid model. Hence, binuclear silver(I)-NHC complexes with longer terminal aliphatic chains have worth to be further studied against human colon cancer for the purpose of drug development.
It is seen that the regioselective functionalizations of halogenated heterocycles play an important role in the synthesis of several types of organic compounds. In this domain, the Suzuki-Miyaura reaction has emerged as a convenient way to build carbon-carbon bonds in synthesizing organic compounds. Some of the most important applications of these reactions can be seen in the synthesis of natural products, and in designing targeted pharmaceutical compounds. Herein, we present the regioselective synthesis of the novel series of 2-(bromomethyl)-5-aryl-thiophenes 3a-i, via Suzuki cross-coupling reactions of various aryl boronic acids with 2-bromo-5-(bromomethyl)thiophene (2).
Carbon Nanotubes (CNTs) are generally nano-scale tubes comprising a network of carbon atoms in a cylindrical setting that compared with silicon counterparts present outstanding characteristics such as high mechanical strength, high sensing capability and large surface-to-volume ratio. These characteristics, in addition to the fact that CNTs experience changes in their electrical conductance when exposed to different gases, make them appropriate candidates for use in sensing/measuring applications such as gas detection devices. In this research, a model for a Field Effect Transistor (FET)-based structure has been developed as a platform for a gas detection sensor in which the CNT conductance change resulting from the chemical reaction between NH3 and CNT has been employed to model the sensing mechanism with proposed sensing parameters. The research implements the same FET-based structure as in the work of Peng et al. on nanotube-based NH3 gas detection. With respect to this conductance change, the I-V characteristic of the CNT is investigated. Finally, a comparative study shows satisfactory agreement between the proposed model and the experimental data from the mentioned research.
Objective. To determine the diagnostic accuracy of placental alpha microglobulin-1 assay and standard diagnostic methods for detecting rupture of membrane. Study Design. Prospective diagnostic study, between June 2011 to November 2011 at a tertiary centre. Initial evaluation included both the standard diagnostic methods for rupture of membranes and placental alpha microglobulin-1 immunoassay. The actual rupture of membranes was diagnosed on review of the medical records after delivery (absence of membrane or a positive pad chart). Main Outcome Measures. Placental alpha microglobulin-1 immunoassay and standard diagnostic methods for diagnosis of rupture of membrane. Results. A total of 211 patients were recruited. At initial presentation, 187 patients (88.6%) had ruptured membranes, while 24 patients (11.4%) had intact membranes. Placental alpha microglobulin-1 immunoassay confirmed rupture of membranes at initial presentation with a sensitivity of 95.7% (179 of 187), specificity of 100% (24 of 24), positive predictive value of 100% (179 of 179), and negative predictive value of 75.0% (24 of 32). By comparison, the conventional standard diagnostic methods had a sensitivity of 78.1% (146 of 187), specificity of 100% (24 of 24), positive predictive value of 100% (146 of 146), and negative predictive value of 36.9% (24 of 65) in diagnosing rupture of membrane. Conclusion. Placental alpha-microglobulin-1 immunoassay is a rapid and accurate method for confirming the diagnosis of rupture of membrane. It was superior to conventional standard diagnostic methods (pooling, nitrazine, and ferning), the nitrazine test alone or fern test alone.
Symmetrical and unsymmetrical dithiocarbamato pyridine solvated and non-solvated complexes of indium(III) with the general formula [In(S2CNRR')3]·n(py) [where py = pyridine; R,R' = Cy, n = 2 (1); R,R' = (i)Pr, n = 1.5 (2); NRR' = Pip, n = 0.5 (3) and R = Bz, R' = Me, n = 0 (4)] have been synthesized. The compositions, structures and properties of these complexes have been studied by means of microanalysis, IR and (1)H-NMR spectroscopy, X-ray single crystal and thermogravimetric (TG/DTG) analyses. The applicability of these complexes as single source precursors (SSPs) for the deposition of β-In2S3 thin films on fluorine-doped SnO2 (FTO) coated conducting glass substrates by aerosol-assisted chemical vapour deposition (AACVD) at temperatures of 300, 350 and 400 °C is studied. All films have been characterized by powder X-ray diffraction (PXRD) and energy dispersive X-ray analysis (EDX) for the detection of phase and stoichiometry of the deposit. Scanning electron microscopy (SEM) studies reveal that precursors (1)-(4), irrespective of different metal ligand design, generate comparable morphologies of β-In2S3 thin films at different temperatures. Direct band gap energies of 2.2 eV have been estimated from the UV-vis spectroscopy for the β-In2S3 films fabricated from precursors (1) and (4). The photoelectrochemical (PEC) properties of β-In2S3 were confirmed by recording the current-voltage plots under light and dark conditions. The plots showed anodic photocurrent densities of 1.25 and 0.65 mA cm(-2) at 0.23 V vs. Ag/AgCl for the β-In2S3 films made at 400 and 350 °C from the precursors (1) and (4), respectively. The photoelectrochemical performance indicates that the newly synthesised precursors are highly useful in fabricating β-In2S3 electrodes for solar energy harvesting and optoelectronic application.
Perovskite-structured lead titanate thin films have been grown on FTO-coated glass substrates from a single-source heterometallic molecular complex, [PbTi(μ2-O2CCF3)4(THF)3(μ3-O)]2 (1), which was isolated in quantitative yield from the reaction of tetraacetatolead(IV), tetrabutoxytitanium(IV), and trifluoroacetic acid from a tetrahydrofuran solution. Complex 1 has been characterized by physicochemical methods such as melting point, microanalysis, FTIR, (1)H and (19)F NMR, thermal analysis, and single-crystal X-ray diffraction (XRD) analysis. Thin films of lead titanate having spherical particles of various sizes have been grown from 1 by aerosol-assisted chemical vapor deposition at 550 °C. The thin films have been characterized by powder XRD, scanning electron microscopy, and energy-dispersive X-ray analysis. An optical band gap of 3.69 eV has been estimated by UV-visible spectrophotometry.
6-Chloro-2-Aryl-1H-imidazo[4,5-b]pyridine derivatives 1-26 were synthesized and characterized by various spectroscopic techniques. All these derivatives were evaluated for their antiglycation, antioxidant and β-glucuronidase potential followed their docking studies. In antiglycation assay, compound 2 (IC50=240.10±2.50μM) and 4 (IC50=240.30±2.90μM) was found to be most active compound of this series, while compounds 3 (IC50=260.10±2.50μM), 6 (IC50=290.60±3.60μM), 13 (IC50=288.20±3.00μM) and 26 (IC50=292.10±3.20μM) also showed better activities than the standard rutin (IC50=294.50±1.50μM). In antioxidant assay, compound 1 (IC50=69.45±0.25μM), 2 (IC50=58.10±2.50μM), 3 (IC50=74.25±1.10μM), and 4 (IC50=72.50±3.30μM) showed good activities. In β-glucuronidase activity, compounds 3 (IC50=29.25±0.50μM), compound 1 (IC50=30.10±0.60μM) and compound 4 (IC50=46.10±1.10μM) showed a significant activity as compared to than standard D-Saccharic acid 1,4-lactonec (IC50=48.50±1.25μM) and their interaction with the enzyme was confirm by docking studies.
Isatin base Schiff bases (1-20) were synthesized, characterized by (1)H NMR and EI/MS and evaluated for α-glucosidase inhibitory potential. Out of these twenty (20) compounds only six analogs showed potent α-glucosidase inhibitory potential with IC50 value ranging in between 2.2±0.25 and 83.5±1.0μM when compared with the standard acarbose (IC50=840±1.73μM). Among the series compound 2 having IC50 value (18.3±0.56μM), 9 (83.5±1.0μM), 11 (3.3±0.25μM), 12 (2.2±0.25μM), 14 (11.8±0.15μM), and 20 (3.0±0.15μM) showed excellent inhibitory potential many fold better than the standard acarbose. The binding interactions of these active analogs were confirmed through molecular docking.
Medicinal plants represent one of the most accessible resources available for snake and scorpion bite among the rural communities of Northern Pakistan. This first ethno-botanical study aimed to document the indigenous knowledge and practices of using plants for snake and scorpion bite disorders in Northern Pakistan.
Pyrus pashia Buch.-Ham. ex D. Don. has been used conventionally by many communities in the Himalayan region for the management of gastrointestinal, respiratory, and vascular complications. Set against this background, this study was carried out to justify the scientific basis to validate folkloric uses of fruits of Pyrus pashia Buch.-Ham. ex D. Don. (Pp.Cr) in traditional systems of medicine.
Introduction: Leptospirosis is a re-emerging zoonotic disease caused by Leptospira bacteria. The clinical manifes-tations of leptospirosis include mild-fever to a severe or even fatal. Increased levels of inflammatory cytokines pro-duced in response to the Leptospira infection by the host immune system were hypothesized as among the causes of severity in leptospirosis. Besides the classical presentation with the triad of febrile, jaundice, and renal failure, patients with leptospirosis also can pose with predominant sign and symptoms of pulmonary involvement. This study aimed to compare the levels of TNF-α, IL-1b, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17A, IL-18, and IL-22 In the plasma of samples of leptospirosis patients with and without pneumonia. Methods: Circulating cytokine levels in plasma were measured in seventeen patients hospitalized and diagnosed with leptospirosis in Malaysia (January 2016 – December 2017) and nineteen healthy individuals as controls. Patients were categorized into leptospirosis without pneumonia (n=12) and with pneumonia (n=5). Cytokine was measured using SimplePlexTM assays (San Jose, CA, USA). Measurement was performed in triplicate and statistical analysis was conducted using Graphpad® Prism v6 (San Diego, CA, USA). Results: Elevation of plasma TNF-α, IL-6, IL-8, IL-10, IL-18, and IL-22 levels were observed among leptospirosis patients with pneumonia compared to without, although no statistical differences were observed between these two groups. Conclusion: There are no significant differences observed between the levels of plasma TNF-α, IL-6, IL-8, IL-10, IL-18, and IL-22 in patients with pneumonia compared to without.
A new micro heat exchanger was analyzed using numerical formulation of conjugate heat transfer for single-phase fluid flow across copper microchannels. The flow across bent channels harnesses asymmetric laminar flow and dean vortices phenomena for heat transfer enhancement. The single-channel analysis was performed to select the bent channel aspect ratio by varying width and height between 35-300 μm for Reynolds number and base temperature magnitude range of 100-1000 and 320-370 K, respectively. The bent channel results demonstrate dean vortices phenomenon at the bend for Reynolds number of 500 and above. Thermal performance factor analysis shows an increase of 18% in comparison to straight channels of 200 μm width and height. Alumina nanoparticles at 1% and 3% concentration enhance the Nusselt number by an average of 10.4% and 23.7%, respectively, whereas zirconia enhances Nusselt number by 16% and 33.9% for same concentrations. On the other hand, thermal performance factor analysis shows a significant increase in pressure drop at high Reynolds number with 3% particle concentration. Using zirconia for nanofluid, Nusselt number of the bent multi-channel model is improved by an average of 18% for a 3% particle concentration as compared to bent channel with deionized water.
Rising prevalence of autism spectrum disorders (ASD) in the last decades has led research to focus on the diagnosis and identification of factors associated with ASD. This paper sought for possible factors that put children at risk for ASD. In this study, we investigated the association between ASD and parental ages, parental age gaps, birth order and birth delivery method in Malaysian population. In this school-based case control study, 465 children with ASD 464 controls participated. Questionnaires were distributed to the parents of the selected children through the respective principals. Among the tested variables, Caesarean section (OR = 1.63, 95% CI 1.20, 2.20), earlier order of birth in the family (OR = 0.68, 95% CI 0.59, 0.77) and increasing gap in parental ages (OR = 1.04, 95% CI 1.001, 1.07) were significantly associated with ASD. This study concludes that Caesarean section, earlier order of birth in the family and increasing gap in parental age are independent risk factors for developing autism among Malaysian children.
In this paper, a simple analysis yet a straight forward method of determining the Planck’s constant by
evaluating the stopping potential of five different colors of light emitting diodes (LEDs) is presented.
The study aimed to identify the Planck’s constant based on the relationship between the potential
difference of LEDs to their respective frequencies under room temperature with low illumination of
ambient light by applying a simple theoretical analysis. The experiment was performed by connecting
the circuit in series connection and the voltage reading of LEDs were recorded and then presented in a
graph of frequency, f versus stopping voltage, Vo. To determine the Planck’s constant, the best fit line
was analyzed and the centroid was also identified in order to find the minimum and maximum errors
due the gradient of the graph. From the analysis, results showed that the Planck constant value was
(5.997 ± 1.520) × 10–34 J.s with approximately 10% of deviation from the actual value. This
demonstrates that a simple analysis can be utilized to determine the Planck’s constant for the purpose
of the laboratory teaching and learning at the undergraduate level and can be served as a starting point
for the students to understand the concept of quantization of energy in Modern Physics more
effectively. This is to further suggest that the Planck’s constant can be identified via a low-cost and
unsophisticated experimental setup.
Dental fluorosis incidence had been reported to be affecting children widely, especially in water-fluoridated ar-ea. As these children grow into young adults, perceived aesthetic problems arise mainly due to their concern with generalized mottled and stained teeth appearance. Fixed prosthodontics treatment involving single anterior tooth in patients with generalized fluorosis condition had been found challenging due to aesthetic restorability to blend with fluorosis condition. Clinical considerations: A simplified procedural direct chair-side technique of mimicking fluorosis condition onto anterior all-ceramic crowns are discussed in this paper. The mimicked fluoro-sis is reversible and has the opportunity to be adjusted according to the patient’s fluorosis condition thus hinder-ing the need to redo the crown in the future. Conclusions: The appearance of anterior all-ceramic crowns with direct chair-side staining technique provided blended and harmonized well with the dental fluorosis condition in both patients thus, giving natural looking smile.
There are various secondary metabolites that have been identified in Polygonum minus Huds. or kesum plant, but
the production is often very low and depending on growth stage. Therefore, elicitation and in vitro techniques have
been suggested as an effective way for inducing secondary metabolites production in plant. This study was conducted
to determine the optimal conditions for P. minus root formation in vitro and to profile the metabolite content from
P. minus root culture with and without elicitor treatment. From the root induction study, it was found that the fresh
weight of induced root for nodal explant in MS liquid media supplemented with 0.5 mg/L NAA and shaken had the
highest production (0.38±0.08 g) compared to other treatments including the control. The results from metabolite
profile showed that the volatile compound of P. minus root produced without any elicitation contained 50.11% aliphatic
(27.59% aldehide, 9.17% alkane and 13.35% others) and 19.39% sesquiterpene (β-caryophyllene, α-bergamotene,
β-farnesene, α-caryophyllene dan β-curcumene) where the dodecanal compound (22.27%) and β-caryophyllene
(8.09%) have the highest percentage value for aliphatic and sesquiterpene group, respectively. Moreover, elicitation of
P. minus root culture using yeast extract at 100 mg/L concentration for 1 day demonstrated the ability to increase the
production of secondary metabolites in many volatile compounds of kesum in vitro root including the sesquiterpene
compounds compared to control treatment and other yeast extract elicitation treatments.
The role of aldose reductase (ALR2) in diabetes mellitus is well-established. Our interest in finding ALR2 inhibitors led us to explore the inhibitory potential of new thiosemicarbazones. In this study, we have synthesized adamantyl-thiosemicarbazones and screened them as aldehyde reductase (ALR1) and aldose reductase (ALR2) inhibitors. The compounds bearing phenyl 3a, 2-methylphenyl 3g and 2,6-dimethylphenyl 3m have been identified as most potent ALR2 inhibitors with IC50 values of 3.99 ± 0.38, 3.55 ± 0.26 and 1.37 ± 0.92 µM, respectively, compared with sorbinil (IC50 = 3.14 ± 0.02 μM). The compounds 3a, 3g, and 3m also inhibit ALR1 with IC50 value of 7.75 ± 0.28, 7.26 ± 0.39 and 7.04 ± 2.23 µM, respectively. Molecular docking was also performed for putative binding of potent inhibitors with target enzyme ALR2. The most potent 2,6-dimethylphenyl bearing thiosemicarbazone 3m (IC50 = 1.37 ± 0.92 µM for ALR2) and other two compound 3a and 3g could potentially lead for the development of new therapeutic agents.
Novel bi-heterocyclic benzamides were synthesized by sequentially converting 4-(1H-indol-3-yl)butanoic acid (1) into ethyl 4-(1H-indol-3-yl)butanoate (2), 4-(1H-indol-3-yl)butanohydrazide (3), and a nucleophilic 5-[3-(1H-indol-3-yl)propyl]-1,3,4-oxadiazole-2-thiol (4). In a parallel series of reactions, various electrophiles were synthesized by reacting substituted anilines (5a-k) with 4-(chloromethyl)benzoylchloride (6) to afford 4-(chloromethyl)-N-(substituted-phenyl)benzamides (7a-k). Finally, the nucleophilic substitution reaction of 4 was carried out with newly synthesized electrophiles, 7a-k, to acquire the targeted bi-heterocyclic benzamides, 8a-k. The structural confirmation of all the synthesized compounds was done by IR, 1 H NMR, 13 C NMR, EI-MS, and CHN analysis data. The inhibitory effects of these bi-heterocyclic benzamides (8a-k) were evaluated against alkaline phosphatase, and all these molecules were identified as potent inhibitors relative to the standard used. The kinetics mechanism was ascribed by evaluating the Lineweaver-Burk plots, which revealed that compound 8b inhibited alkaline phosphatase non-competitively to form an enzyme-inhibitor complex. The inhibition constant Ki calculated from Dixon plots for this compound was 1.15 μM. The computational study was in full agreement with the experimental records and these ligands exhibited good binding energy values. These molecules also exhibited mild cytotoxicity toward red blood cell membranes when analyzed through hemolysis. So, these molecules might be deliberated as nontoxic medicinal scaffolds to render normal calcification of bones and teeth.