Carbon nanoparticles have been widely used in various applications. However, they are commonly known to have low dispersibility and chemical inertness which limit their practical ability in medical or biological area. Some studies have been performed to modify carbon nanoparticles such as carbon nanotubes using ultraviolet (UV)-Ozone system. However, little is known on the effects of such system towards other types of carbon nanoparticles such as mesoporous hollow carbon nanoparticles (MHCNs). Thus, in this study, improvement of MHCNs physiochemical properties have been studied using UV-Ozone treatment for the first time. The treatment was conducted in water as dispersant agent at ozone flowrate of 1.0 L/min and exposure time of 45 min. SEM images observed that MHCNs morphology and surface structure remain intact after the treatment. Observations on the dispersibility of MHCNs in phosphate buffered saline (PBS) solution shows that the dispersibility was improved compared to the untreated ones. This was supported by the low Z-average and PDI values of treated MHCNs obtained at ~400 nm and 0.2, respectively when compared to the untreated MHCNs which was obtained at 970 nm and 0.417, respectively. Thermogravimetric analysis (TGA) showed an increased in weight loss of treated MHCNs at the lower temperature compared to untreated MHCNs. Results from Fourier Transform Infrared (FTIR) showed an increase number of new functional groups that includes carboxylic acid group presence at the surface of treated MHCNs which contributes to the improvement of their dispersibility, thermal properties and chemical functionality. These findings opened a new possibility of using UV-Ozone treatment to improve physicochemical properties of MHCNs for medical area such as in drug delivery application in addition to their excellent storage and carrier system.
The compatibility and performance of an Isoreticular Metal-Organic Frameworks (IRMOF-1) impregnated with choline-based ionic liquids (ILs) for selective adsorption of H2S/CO2, were studied by molecular dynamics (MD) simulation. Cholinium alanate ([Chl][Ala]) was nominated as the suitable IL for impregnation into IRMOF-1, consistent with the low RMSD values (0.546 nm, 0.670 nm, 0.776 nm) at three IL/IRMOF-1 w/w ratios (WIL/IRMOF-1 = 0.4, 0.8, and 1.2). The [Chl]+ and [Ala]- ion pair was located preferentially around the carboxylate group within the IRMOF-1 framework, with the latter interacting strongly with the host than the [Chl]+. Results of radius of gyration (Rg) and root mean square displacement (RMSD) revealed that a ratio of 0.4 w/w of IL/IRMOF-1 (Rg = 1.405 nm; RMSD = 0.546 nm) gave the best conformation to afford an exceptionally stable IL/IRMOF-1 composite. It was discovered that the IL/IRMOF-1 composite was more effective in capturing H2S and CO2 compared to pristine IRMOF-1. The gases adsorbed in higher quantities in the IL/IRMOF-1 composite phase compared to the bulk phase, with a preferential adsorption for H2S, as shown by the uppermost values of adsorption ( [Formula: see text] = 17.954 mol L-1 bar-1) and an adsorption selectivity ( [Formula: see text] = 43.159) at 35 IL loading.
Current study is based on the biology-oriented drug synthesis (BIODS) of 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl aryl carboxylate derivatives 1-26, by treating metronidazole with different aryl and hetero-aryl carboxylic acids in the presence of 1,1'-carbonyl diimidazole (CDI) as a coupling agent. Structures of all synthetic derivatives were confirmed with the help of various spectroscopic techniques such as EI-MS, (1)H -NMR and (13)C NMR. CHN elemental analyses were also found in agreement with the calculated values. Synthetic derivatives were evaluated to check their β-glucuronidase inhibitory activity which revealed that except few derivatives, all demonstrated good inhibition in the range of IC50 = 1.20 ± 0.01-60.30 ± 1.40 μM as compared to the standard d-saccharic acid 1,4-lactone (IC50 = 48.38 ± 1.05 μM). Compounds 1, 3, 4, 6, 9-19, and 21-24 were found to be potent analogs and showed superior activity than standard. Limited structure-activity relationship is suggested that the molecules having electron withdrawing groups like NO2, F, Cl, and Br, were displayed better activity than the compounds with electron donating groups such as Me, OMe and BuO. To verify these interpretations, in silico study was also performed, a good correlation was observed between bioactivities and docking studies.
A series of monoamide isomers have been successfully synthesised and characterised using combination of common spectroscopic techniques such Fourier Transform Infrared (FT-IR), 1H and 13C Nuclear Magnetic Resonance (NMR) and Ultraviolet-visible (UV-vis). The monoamide compounds namely 6-(3-methyl-pyridin-2-ylcarbamoyl)-pyridine2-carboxylic acid methyl ester (L1), 6-(4-methyl-pyridin-2-ylcarbamoyl)-pyridine-2-carboxylic acid methyl ester (L2), 6-(5-methyl-pyridin-2-ylcarbamoyl)-pyridine-2-carboxylic acid methyl ester (L3) and 6-(6-methyl-pyridin-2ylcarbamoyl)-pyridine-2-carboxylic acid methyl ester (L4) were prepared from reaction between 6-(methoxycarbonyl) pyridine-2-carboxylic acid with 2-amino-N-methylpyridine (where N = 3, 4, 5 and 6) by using acyl chloride reaction. In this present studies, the synthesis and characterization of these compounds are discussed along with the inductive effects contributed by methyl substituted groups at the pyridine ring.
Salmonella enterica serovar Typhi (S. Typhi) is strictly a human intracellular pathogen. It causes acute systemic (typhoid fever) and chronic infections that result in long-term asymptomatic human carriage. S. Typhi displays diverse disease manifestations in human infection and exhibits high clonality. The principal factors underlying the unique lifestyle of S. Typhi in its human host during acute and chronic infections remain largely unknown and are therefore the main objective of this study.
This study is based on the removal of methylene blue (MB) from aqueous solution by cost effective and biodegradable adsorbent carboxymethyl starch grafted polyvinyl pyrolidone (Car-St-g-PVP). The Car-St-g-PVP was synthesized by grafting vinyl pyrolidone onto carboxymethyl starch by free radical polymerization reaction. The structure and different properties of Car-St-g-PVP were determined by 1H NMR, FT-IR, XRD, TGA and SEM. A series of batch experiments were conducted for the removal of MB, The adsorption affecting factors such as temperature, contact time, initial concentration of MB dye, dose of Car-St-g-PVP and pH were studied in detail. The other parameters like the thermodynamic study, kinetics and isothermal models were fitted to the experimental data. The results showed that pseudo 2nd order kinetics and Langmuir's adsorption isotherms were best fitted to experimental data with regression coefficient R2 viz. 0.99 and 0.97. The kinetic study showed that the adsorption mechanism favored chemisorption. The Gibbs free energy (ΔG°) for the adsorption process was found to be -7.31 kJ/mol, -8.23 kJ/mol, -9.00 kJ/mol and -10.10 kJ/mol at 25 °C, 35 °C, 45 °C and 55 °C respectively. The negative values of ΔG° suggested the spontaneous nature of the adsorption process. Similarly, the positive values of entropy (ΔS°) and enthalpy (ΔH°) 91.27 J/k.mol and 19.90 kJ/mol showed the increasing randomness and endothermic nature of the adsorption process. The value of separation factor (RL) was found to be less than one (RL
In the current research work, a facile synthesis of a series of novel thiophene-based derivatives of 5-bromothiophene-2-carboxylic acid ( 1 ) have been synthesized. All analogs ( 5a - 5e , 10a - 10f ) were obtained from the coupling reaction of 5-bromothiophene-2-carboxylic acid ( 1 ) and different arylboronic acids with moderate-to-good yields under controlled and optimal conditions. The structures of the newly synthesized compounds were characterized through spectral analysis and their spasmolytic activity, and most of the compounds exhibited potentially good spasmolytic effect. Among the synthesized analogs, compound phenethyl 5-(3,4-dichlorophenyl)thiophene-2-carboxylate ( 10d ) particular showed an excellent spasmolytic effect with an EC 50 value of 1.26. All of the compounds were also studied for their structural and electronic properties by density functional theory (DFT) calculations. Through detailed insight into frontier molecular orbitals of the compounds and their different reactivity descriptors, it was found that the compounds 10c and 5c are the most reactive, while 10a is the most stable in the series. Furthermore, compounds 10c and 5c showed a very good NLO response with the highest β values.
A new series of 4H-chromene-3-carboxylate derivatives were synthesized using multicomponent reaction of salicylaldehyde, ethyl acetoacetate and dimedone in ethanol with K3PO4 as a catalyst at 80 °C. The structures of all newly synthesized compounds were confirmed by spectral techniques viz. IR, 1H NMR, 13C NMR, and LCMS analysis. The newly synthesized compounds 4a to 4j were screened against elastase enzyme. Interestingly, all these compounds found to be potent elastase inhibitors with much lower IC50 value. The compound 4b was found to be most potent elastase inhibitor (IC50 = 0.41 ± 0.01 µM) amongst the synthesized series against standard Oleanolic Acid (IC50 value = 13.45 ± 0.0 µM). The Kinetics mechanism for compound 4b was analyzed by Lineweaver-Burk plots which revealed that compound inhibited elastase competitively by forming an enzyme-inhibitor complex. Along with this, all the synthesized compounds (4a - 4j) exhibits excellent DPPH free radical scavenging ability. The inhibition constant Ki for compound 4b was found to be 0.6 µM. The computational study was comprehensible with the experimental results with good docking energy values (Kcal/mol). Therefore, these molecules can be considered as promising medicinal scaffolds for the treatment of skin-related maladies.
This study has evaluated the effect of functionalizing surface charges of hydroxyapatite on the modulation of loading and release of curcumin nanoparticles. The increase in loading and release of curcumin nanoparticles indirectly translates to enhanced anti-cancer effect. Owing to the hydrophobic characteristics of curcumin which have resulted in low bioavailability in cancer cells, the engineering curcumin into nanoparticles is therefore a viable solution to overcomes its limitation. In order to maintain a sustained release profile of curcumin nanoparticles, curcumin nanoparticles were loaded (Cur-NPs) onto hydroxyapatite (HA) via physical adsorption. To regulate the adsorption capacity of Cur-NPs onto HA, we functionalized HA with different carboxylic acids (lactic acid, tartaric acid and citric acid). The presence of carboxylic groups on HA significantly affected the binding and the release profile of Cur-NPs. The effects of Cur-NPs loaded HA were evaluated on breast cancer cell line (MCF-7), which included cell proliferation, cellular uptake of Cur-NPs, apoptosis and cell cycle analysis. The results showed that carboxylic acid-functionalized HA demonstrated higher anti-proliferating activity and time dependent cytoplasmic uptake of Cur-NPs in MCF-7 cells compared to unmodified HA. In addition, Cur-NPs loaded on functionalized HA induced higher apoptosis and cell cycle arrest in MCF-7 cells compared to unmodified HA. The present study indicates that the delivery of Cur-NPs to breast cancer using carboxylic acid-functionalized HA carrier could improve their anti-cancer activities.
Microtubule Targeting Agents (MTAs) including paclitaxel, colchicine and vinca alkaloids are widely used in the treatment of various cancers. As with most chemotherapeutic agents, adverse effects and drug resistance are commonly associated with the clinical use of these agents. Methyl 2-(5-fluoro-2-hydroxyphenyl)-1H- benzo[d]imidazole-5-carboxylate (MBIC), a benzimidazole derivative displays greater toxicity against various cancer compared to normal human cell lines. The present study, focused on the cytotoxic effects of MBIC against HeLa cervical cancer cells and possible actions on the microtubule assembly.
We recently reported that methyl 2-(-5-fluoro-2-hydroxyphenyl)-1H-benzo[d]imidazole-5-carboxylate (MBIC) is a microtubule targeting agent (MTA) with multiple mechanisms of action including apoptosis in two human breast cancer cell-lines MCF-7 and MDA-MB-231. In the present study, investigation of early molecular events following MBIC treatment demonstrated the induction of autophagy. This early (<24 h) response to MBIC was characterized by accumulation of autophagy markers; LC3-II, Beclin1, autophagic proteins (ATGs) and collection of autophagosomes but with different variations in the two cell-lines. MBIC-induced autophagy was associated with generation of reactive oxygen species (ROS). In parallel, an increased activation of SAPK/JNK pathway was detected, as an intersection of ROS production and induction of autophagy. The cytotoxic effect of MBIC was enhanced by inhibition of autophagy through blockage of SAPK/JNK signaling, suggesting that MBIC-induced autophagy, is a possible cellular self-defense mechanism against toxicity of this agent in both breast cancer cell-lines. The present findings suggest that inhibition of autophagy eliminates the cytoprotective activity of MDA-MB-231 and MCF-7 cells, and sensitizes both the aggressive and non-aggressive human breast cancer cell-lines to the cytotoxic effects of MBIC.
Microtubule Targeting Agents (MTAs) induce cell death through mitotic arrest, preferentially affecting rapidly dividing cancer cells over slowly proliferating normal cells. Previously, we showed that Methyl 2-(-5-fluoro-2-hydroxyphenyl)-1H-benzo[d]imidazole-5-carboxylate (MBIC) acts as a potential MTA. In this study, we demonstrated that MBIC exhibits greater toxicity towards non-aggressive breast cancer cell-line, MCF-7 (IC50 = 0.73 ± 0.0 μM) compared to normal fibroblast cell-line, L-cells (IC50 = 59.6 ± 2.5 μM). The IC50 of MBIC against the aggressive breast cancer cell-line, MDA-MB-231 was 20.4 ± 0.2 μM. We hypothesized that the relatively high resistance of MDA-MB-231 cells to MBIC is associated with p53 mutation. We investigated p53 and three of its downstream proteins: survivin, cyclin dependent kinase (Cdk1) and cyclin B1. Following treatment with MBIC, survivin co-immunoprecipitated with caspases with higher affinity in MDA-MB-231 compared to MCF-7 cells. Furthermore, silencing survivin caused a 4.5-fold increase in sensitivity of MDA-MB-231 cells to MBIC (IC50 = 4.4 ± 0.3). In addition, 4 weeks of MBIC administration in MDA-MB-231 cells inoculated BALB/c nude mice resulted in 79.7% reduction of tumor volume compared to the untreated group with no severe sign of toxicity. Our results demonstrated MBIC has multiple anti-tumor actions and could be a potential drug in breast cancer therapy.
A new dichlorinated pulvinic acid derivative, methyl-3',5'-dichloro-4,4'-di-O-methylatromentate, was isolated from the fruiting body of a Scleroderma sp. The structure was determined using spectroscopic methods, and an X-ray analysis was carried out for confirmation of the structure. Compound was found to display moderate antimicrobial activity against Bacillus subtilis.
The performances of various anhydrous and aqueous choline chloride-dicarboxylic acid based deep eutectic solvents (DESs) were evaluated for furfural production from oil palm fronds without any additional catalyst. The effects of different carbon chain length dicarboxylic acids and water content in each DES on furfural production were investigated. Oil palm fronds, DES and water (0-5 ml) were mixed and reacted in an oil bath (60-300 min). Reacted oil palm fronds had the potential to be reused as cellulose-rich-valuable by-products. At 100 °C, aqueous choline chloride-oxalic acid (16.4 wt% H2O) produced the highest furfural yield of 26.34% and cellulose composition up to 72.79% in the reacted oil palm fronds. Despite operating at suitable reaction duration for dicarboxylic acid with longer carbon chain length, aqueous choline chloride-malonic acid and aqueous choline chloride-succinic acid performed poorly with furfural yield of less than 1%.
Three fluorescent organic compounds-furocoumarin (FC), dansyl aniline (DA), and 7-hydroxycoumarin-3-carboxylic acid (CC)-are mixed to produce almost pure white light emission (WLE). This novel mixture is immobilised in silica aerogel and applied as a coating to a UV LED to demonstrate its applicability as a low-cost, organic coating for WLE via simultaneous emission. In ethanol solution and when immobilised in silica aerogel, the mixture exhibits a Commission Internationale d'Eclairage (CIE) chromaticity index of (0.27, 0.33). It was observed that a broadband and simultaneous emission involving coumarin carboxylic acid, furocoumarin and dansyl aniline played a vital role in obtaining a CIE index close to that of pure white light.
Perfluorooctanoic acid (PFOA) has been identified as the most toxic specie of the family of perfluorinated carboxylic acids (PFCAs). It has been widely distributed and frequently detected in environmental wastewater. The compound's unique features such as inherent stability, rigidity, and resistance to harsh chemical and thermal conditions, due to its multiple and strong C-F bonds have resulted in its resistance to conventional wastewater remediations. Photolysis and bioremediation methods have been proven to be inefficient in their elimination, hence this article presents intensive literature studies and summarized findings reported on the application of advanced oxidation processes (AOPs) and photocatalytic degradation techniques as the best alternatives for the PFOA elimination from wastewater. Techniques of persulfate, photo-Fenton, electrochemical, photoelectrochemical and photocatalytic degradation have been explored and their mechanisms for the degradation and defluorination of the PFOA have been demonstrated. The major advantage of AOPs techniques has been centralized on the generation of active radicals such as sulfate (SO4•-) hydroxyl (•OH). While for the photocatalytic process, photogenerated species (electron (e) and holes (h + vb)) initiated the process. These active radicals and photogenerated species possessed potentiality to attack the PFOA molecule and caused the cleavage of the C-C and C-F bonds, resulting in its efficient degradation. Shorter-chain PFCAs have been identified as the major intermediates detected and the final stage entails its complete mineralization to carbon dioxide (CO2) and fluoride ion (F-). The prospects and challenges associated with the outlined techniques have been highlighted for better understanding of the subject matter for the PFOA elimination from real wastewaters.
Perfluoroalkyl carboxylic acids (PFCAs) are sub-class of perfluoroalkyl substances commonly detected in water matrices. They are persistent in the environment, hence highly toxic to living organisms. Their occurrence at trace amount, complex nature and prone to matrix interference make their extraction and detection a challenge. This study consolidates current advancements in solid-phase extraction (SPE) techniques for the trace-level analysis of PFCAs from water matrices. The advantages of the methods in terms of ease of applications, low-cost, robustness, low solvents consumption, high pre-concentration factors, better extraction efficiency, good selectivity and recovery of the analytes have been emphasized. The article also demonstrated effectiveness of some porous materials for the adsorptive removal of the PFCAs from the water matrices. Mechanisms of the SPE/adsorption techniques have been discussed. The success and limitations of the processes have been elucidated.
A new adenine-containing metal-organic framework (MOF), [Zn4O(adenine)4(benzene-1,3-dicarboxylate)4Zn2] (named as ZnBDCA), was synthesized solvothermally. ZnBDCA possesses high quantum yield (>50%) and nano-channels that can encapsulate acriflavine molecules to build a host-guest chemopalette for approaching white-light emission.
Single-walled carbon nanotubes (SWCNTs) are carbon-based nanomaterials that possess immense industrial potential. Despite accumulating evidence that exposure to SWCNTs might be toxic to humans, our understanding of the mechanisms for cellular toxicity of SWCNTs remain limited. Here, we demonstrated that acute exposure of short (1-3μm) and regular-length (5-30μm) pristine, carboxylated or hydroxylated SWCNTs inhibited cell proliferation in human somatic and human stem cells in a cell type-dependent manner. The toxicity of regular-length pristine SWCNT was most evidenced in NP69>CYT00086>MCF-10A>MRC-5>HaCaT > HEK-293T>HepG2. In contrast, the short pristine SWCNTs were relatively less toxic in most of the cells being tested, except for NP69 which is more sensitive to short pristine SWCNTs as compared to regular-length pristine SWCNTs. Interestingly, carboxylation and hydroxylation of regular-length SWCNTs, but not the short SWCNTs, significantly reduced the cytotoxicity. Exposure of SWCNTs also induced caspase 3 and 9 activities, mitochondrial membrane depolarization, and significant apoptosis and necrosis in MRC-5 embryonic lung fibroblasts. In contrast, SWCNTs inhibited the proliferation of HaCaT human keratinocytes without inducing cell death. Further analyses by gene expression profiling and Connectivity Map analysis showed that SWCNTs induced a gene expression signature characteristic of heat shock protein 90 (HSP90) inhibition in MRC-5 cells, suggesting that SWCNTs may inhibit the HSP90 signaling pathway. Indeed, exposure of MRC-5 cells to SWCNTs results in a dose-dependent decrease in HSP90 client proteins (AKT, CDK4 and BCL2) and a concomitant increase in HSP70 expression. In addition, SWCNTs also significantly inhibited HSP90-dependent protein refolding. Finally, we showed that ectopic expression of HSP90, but not HSP40 or HSP70, completely abrogated the cytotoxic effects of SWCNTs, suggesting that SWCNT-induced cellular toxicity is HSP90 dependent. In summary, our findings suggest that the toxic effects of SWCNTs are mediated through inhibition of HSP90 in human lung fibroblasts and keratinocytes.
Lactobacillus acidophilus is categorized as a probiotic strain because of its beneficial effects in human health and prevention of disease transmission. This study is aimed to characterize the probiotic potential of L. acidophilus 36YL originally isolated from the vagina of healthy and fertile Iranian women. The L. acidophilus 36YL strain was identified using 16S rDNA gene sequencing and characterized by biochemical methodologies, such as antibiotics susceptibility, antimicrobial activity, and acid and bile resistance. The bioactivity of the secretion of this strain on four human cancer cell lines (AGS, HeLa, MCF-7, and HT-29) and one normal cell line (HUVEC) was evaluated by cytotoxicity assay and apoptosis analysis. This newly isolated strain was found to exhibit notable probiotic properties, such as admirable antibiotic susceptibility, good antimicrobial activity, and favorable resistance to acid and bile salt. The results of bioactivity assessment demonstrated acceptable anticancer effects on the four tested cancer cell lines and negligible side effects on the assayed normal cell line. Our findings revealed that the anticancer effect of L. acidophilus 36YL strain secretions depends on the induction of apoptosis in cancer cells. L. acidophilus 36YL strain is considered as a nutraceutical alternative or a topical medication with a potential therapeutic index because of the absence of cytotoxicity to normal cells, but effective toxicity to cancer cell lines.