Methoxy Substitution Research Articles

Antimicrobial Activity Evaluation of Newly Synthesized N,N-Disubstituted Taurinamidobenzenesulfonamide Derivatives

Herein we synthesized 6 new N,N-disubstituted taurinamidobenzensulfonamide derivatives and characterized their structures by means of 1H and 13C NMR, HR-MS analysis. In addition, their in vitro antibacterial and antifungal activities were tested against two gram-positive, two gram-negative bacteria, and two fungal strains by using broth microdilution method. Compounds 1 (methoxy substitution) and 2 (methyl substitution) displayed the best antibacterial activity against Escherichia coli and Staphylococcus aureus, respectively. E. faecalis was affected by compounds 1, 2, 4, and 6, becoming the most susceptible pathogen compared to other tested bacterial and fungal strains. Interestingly, changing fluoro atom in compound 6 with the chloro atom, as in compound 5, deteriorated the antibacterial activity against all bacterial strains. As a result, these results provide us to investigate the relationship between structural changes and antibacterial/antifungal activity, which can be further used to develop more effective taurine derivatives.

Introducing methoxy or fluorine substitutions on the conjugated side chain to reduce the voltage loss of organic solar cells

Herein, three benzotriazole (BTA)-based polymers and a fused benzotriazole-based small molecule were constructed to realize a relatively high power conversion efficiency (PCE) of above 11% with a high open-circuit voltage (VOC) approaching 0.99 V.

Intramolecular charge transfer excitation induced by CH3O substitution in the 3-methoxy-1-propoxy radical.

The oxy-substituted alkoxy radicals are generated from the oxidation of ethers. Their degradation path affects ozone production and the formation of the secondary organic aerosol in the atmosphere. In this work, three alkoxy radicals with methoxy (CH3O) substitution at β, γ, and δ carbon are studied using laser-induced fluorescence (LIF) spectroscopy and theoretical calculation methods. A charge transfer (CT) excited state induced by the CH3O substitution is identified to be because of the intramolecular electron transfer from the C-O-C p orbital to the radical O p orbital. Comparison of the structure and CT transition strength between GGt and TTt conformers of the 3-methoxy-1-propoxy radical (CH3OCH2CH2CH2O) suggests that this long-range charge transfer effect is mainly a through-bond interaction. The CT excited state of CH3OCH2CH2CH2O has a conical intersection with the CO σ → O p excited state, which, hence, changes the LIF spectrum of the radical. Only the decomposition product HCHO was observed in the LIF spectrum of β substituted radical CH3OCH2CH2O. For δ substituted radical CH3OCH2CH2CH2CH2O, the substitution effect on the radical stability is negligible and its LIF spectrum is close to that of unsubstituted alkoxy radicals. The results provide information for understanding the degradation chemistry of oxygenated hydrocarbon molecules in the atmosphere.

Studies on imidazo[2,1-b][1,3]benzothiazole derivatives as new radiosensitizers

The synthesis and characterization of potent 7-substituted-2-(4-substitutedphenyl)imidazo[2,1-b][1,3]benzothiazoles as effective radiosensitizers and anticarcinogenic compound is reported. The activity is determined against human liver cancer Hep G2 cell line, two parental melanoma cell lines (human melanoma cell line, A375C and mouse melanoma cell line, A375C). The compounds 7-sulfonamide-2-(4-fluorophenyl)imidazo[2,1-b][1,3]benzothiazole (3f, IC50 = 0.097 μM) and 7-sulfonamide-2-(4-methylphenyl)imidazo[2,1-b][1,3]benzothiazole (3g, IC50 = 0.114 μM) exhibited considerable in vitro anticancer activity against Hep G2 cell line while 7-bromo-2-(4-fluorophenyl)imidazo[2,1-b][1,3]benzothiazole showed effectiveness against both parental melanoma cell lines (3c, IC50 = 0.04 and 0.052 μM). Further the active molecules 3f, 3g and 3h are tested for radiosensitizing activity over Hep G2 cell line at 4 Gy, with the comet formed at 0.054 μM . Similarly, 3c tested against two parental melanoma cell lines, it has proven to be more potent when combined with 2 Gy ϒ-radiation. The present study reveals that presence of sulfonamide in combination with methoxy substitution enhanced DNA fragmentation and there by acting as effective derivative for Hepatocellular carcinoma.

Potential Anti-Acetylcholinesterase Activity of Cassia timorensis DC.

Seventeen methanol extracts from different plant parts of five different Cassia species, including C. timorensis, C. grandis, C. fistula, C. spectabilis, and C. alata were screened against acetylcholinesterase (AChE). C. timorensis extracts were found to exhibit the highest inhibition towards AChE whereby the leaf, stem, and flower methanol extracts showed 94–97% inhibition. As far as we are aware, C. timorensis is one of the least explored Cassia spp. for bioactivity. Further fractionation led to the identification of six compounds, isolated for the first time from C. timorensis: 3-methoxyquercetin (1), benzenepropanoic acid (2), 9,12,15-octadecatrienoic acid (3), β-sitosterol (4), stigmasterol (5), and 1-octadecanol (6). Compound 1 showed moderate inhibition towards AChE (IC50: 83.71 μM), while the other compounds exhibited poor to slightly moderate AChE inhibitory activity. Molecular docking revealed that the methoxy substitution of 1 formed a hydrogen bond with TYR121 at the peripheral anionic site (PAS) and the hydroxyl group at C5 formed a covalent hydrogen bond with ASP72. Additionally, the OH group at the C3′ position formed an interaction with the protein at the acyl pocket (PHE288). This possibly explains the activity of 1 in blocking the entry of acetylcholine (ACh, the neurotransmitter), thus impeding the hydrolysis of ACh.

GC–MS analysis of N-(bromodimethoxybenzyl)-2-, 3-, and 4-methoxyphenethylamines: Inverse analogues of the psychoactive 25B-NBOMe drug

The substituted phenethylamine analogues in this study are derivatives of N-(2-methoxybenzyl)-4-bromo-2,5-dimethoxyphenethylamine (25B-NBOMe) having the reverse substitution pattern for the two aromatic rings. These compounds contain only a single methoxy substituent in the phenethylamine part, and a bromodimethoxy substitution pattern in the benzyl portion. The regioisomers were prepared with variations in the substitution pattern in both the bromodimethoxy substitution pattern of the benzyl part as well as the methoxy substitution pattern in the phenethylamine part. The nine regioisomeric compounds were prepared from the regioisomeric 2-, 3-, and 4- methoxyphenethylamines via N-reductive alkylation with the three regioisomeric 2,4,5-substituted bromodimethoxybenzaldehydes.The EI-MS spectra of these regioisomers gave two major bromine containing ions at m/z 229/231 (base peak) and 258/260 and two non-brominated fragments at m/z 91 and 121. The relative abundance of the m/z 91 was higher for the 2-methoxyphenethylamine substituted isomers and the relative abundance of the m/z 121 fragment was higher in the 4-methoxy substituted isomers. The gas chromatographic separation for the regioisomeric methoxyphenethylamines of each bromodimethoxybenzyl aromatic ring substitution pattern showed the 2-methoxyphenethylamine substituted isomer eluted first followed by the 3-substituted isomer and the 4-methoxyphenethylamine substituted isomer was the last to elute and the three bromodimethoxybenzyl regioisomers for the 2-methoxyphenethylamine subseries were resolved as the trifluoroacetamides. The EI-MS for the TFA derivatives of the 2-bromo-4,5-dimethoxybenzyl substituted isomer gave unique fragment ions resulting from displacement of bromine from the molecular ion. This fragmentation pathway was confirmed using the model compounds N-(2-, 3- and 4-bromobenzyl)phenethylamine trifluoroacetamides.

Evaluation of Ligustrazine-Based Synthetic Compounds for their Antiproliferative Effects.

Ligustrazine and chalcones have been reported previously for various biological activities including anticancer effects. Based on the multitargeted biological activities approach of ligustrazine-based chalcones, in the current study 18 synthetic ligustrazine-containing α, β-unsaturated carbonyl-based 1, 3- Diphenyl-2-propen-1-one derivatives were evaluated for their inhibitory effects on the growth of five different types of cancer cells. All the compounds were evaluated for anticancer effects on various cancer cell lines by propidium iodide fluorescence assay and various other assays were performed for mechanistic studies. A majority of compounds exhibited strong inhibition of cancer cells, especially synthetic compounds 4a and 4b, bearing 1-Pyridin-3-yl-ethanone as a ketone moiety in the main structural backbone were found to be most powerful inhibitors of cancer cell growth. Nine most active compounds among the whole series were selected for further studies related to different cancer targets, including EGFR TK kinases, tubulin polymerization, KAF and BRAFV600E. Synthetic derivatives, including 4a-b and 5a-b showed a multitarget approach and strong inhibitory effects on EGFR, FAK and BRAF while three compounds, including 3e bearing methoxy substitution, 4a and 4b with 1-pyridin-3-yl-ethanone moiety showed the inhibition of tubulin polymerization.

Density functional theoretical tailoring of electronic effect through various substituents on calix[4]arene‐crown‐6 for efficient Cs+ ion encapsulation and extraction

AbstractThe structure, energetic, and quantum chemical descriptors of Cs+ complexes of calix[4]arene‐crown‐6 (C4C6) and substituted C4C6, that is, 1,3 alternate‐diethoxy C4C6, are reported here based on the analysis of results obtained using density functional theory (DFT). Substitution of benzo group in both C4C6 and 1,3 alternate‐diethoxy C4C6 resulted in a reduction of binding energy (BE). Further substitution of the benzo group with methyl, methoxy, and amino groups leads to an increase in BE, and nitro substitution leads to decrease in BE for C4C6, whereas in the case of 1,3 alternate‐diethoxy calix[4]arenebenzocrown‐6, methoxy substitution leads to the highest BE compared to other complexes. The calculated Gibbs free energy, ΔGgas also followed the same order as BE in the case of 1,3 alternate‐diethoxy C4C6 and their substituted ligands. Furthermore, the ΔG of complexation was computed using a thermodynamic cycle with conductor‐like screening model in different solvents: toluene, chloroform, octanol, and nitrobenzene. The values of ΔGext are found to be increased with an increase in the dielectric constant of the solvent and were found to be highest in the nitrobenzene. The atoms in molecule analysis reveals partial ionic character in the CsO bond. Among all the studied complexes, 1,3 alternate‐diethoxy calix[4]arene 3′‐methoxy benzo crown‐6 displays highest ΔGext in nitrobenzene. The calculated value of ∆∆Gext (∆∆G = ∆GCs+ − ∆GNa+) is found to be −41.82 kcal/mol with 1,3 alternate‐diethoxy calix[4]arene 3′‐methoxy benzocrown‐6, which is higher than that obtained with calix [4] bis‐crown‐6 (−5.24 kcal/mol). The newly designed ligand might be suitable for the selective extraction of Cs+ over Na+ in the reprocessing of nuclear waste and thus invites experimentalists to test this DFT finding in the laboratory.

Synthesis, anti-cancer evaluation and molecular docking studies of aryl bisindole derivatives

Abstract A simple and efficient method has been developed for the synthesis of aryl bis-indolyl derivatives (9a-9k) by the catalytic amount of 18-Crown-6 and evaluated for their cytotoxicity using lung cancer, breast cancer, colon and melanoma cancer cell lines. Among them, compounds 9f and 9i with methoxy substitutions on phenyl ring was found be to be potent inhibitors (IC50 = 0.11 to 0.19 µM) of all the tested cell lines. Compound 9c with difluoro substitution on phenyl ring was inhibited first three cell lines (IC50 = 0.12 to 0.15 µM) except melanoma. Compound 9h with both chloro and fluoro on phenyl ring were found to be having the higher potency against only lung cancer cell line (IC50 = 0.11 µM). These compounds showed higher anticancer potency than Adriamycin drug (0.9 to 3.5 µM). Molecular docking studies have been carried out to understand the binding modes of the active and inactive compounds.

Teaching old precursors new tricks: Fast room temperature synthesis of surfactant-free colloidal platinum nanoparticles

A fast, simple, instrument-free room temperature synthesis of stable electroactive surfactant-free colloidal Pt nanoparticles in alkaline methanol and methanol-water mixtures is presented. Pair distribution function (PDF) analysis suggests that methoxy substitution of chloride ligands from H2PtCl6 occurs in methanol. X-ray absorption spectroscopy (XAS) studies and UV–vis measurements show that solutions of H2PtCl6 in methanol age and are reduced to Pt(II) species over time. These species are ideal precursors to significantly reduce the induction period typically observed in colloidal Pt nanoparticle syntheses as well as the temperature needed to form nanoparticles. The room temperature synthesis presented here allows designing simple in situ studies of the nanoparticle formation. In situ infra-red spectroscopy gives insight into the formation and stabilization mechanism of surfactant-free nanoparticles by CO surface groups. Finally, the surfactant-free nanoparticles ca. 2–3 nm in diameter obtained are shown to be readily active electrocatalysts e.g. for methanol oxidation. The synthesis approach presented bears several advantages to design new studies and new syntheses of surfactant-free colloidal nanomaterials.

Bioactivity and Molecular Docking Studies of Derivatives from Cinnamic and Benzoic Acids.

Over the last decade, there has been a dramatic increase in the prevalence and gravity of systemic fungal diseases. This study aimed therefore at evaluating the antifungal potential of ester derivatives of benzoic and cinnamic acids from three Candida species. The compounds were prepared via Fischer esterification, and the antifungal assay was performed by the microdilution method in 96-well microplates for determining the minimal inhibitory concentrations (MICs). The findings of the antifungal tests revealed that the analogue compound methyl ferulate, methyl o-coumarate, and methyl biphenyl-3-carboxylate displayed an interesting antifungal activity against all Candida strains tested, with MIC values of 31.25-62.5, 62.5-125, and 62.5 μg/ml, respectively. A preliminary Structure-Activity Relationship study of benzoic and cinnamic acid derivatives has led to the recognition of some important structural requirements for antifungal activity. The results of molecular docking indicate that the presence of the enoate moiety along with hydroxyl and one methoxy substitution in the phenyl ring has a positive effect on the bioactivity of compound 7 against Candida albicans. These observations further support the hypothesis that the antifungal activity of compound 7 could be due to its binding to multiple targets, specifically to QR, TS, and ST-PK. Additional experiments are required in the future to test this hypothesis and to propose novel compounds with improved antifungal activity.

Design, synthesis, in vitro and in vivo biological evaluation of 2-amino-3-aroylbenzo[b]furan derivatives as highly potent tubulin polymerization inhibitors

A new class of inhibitors of tubulin polymerization based on the 2-amino-3-(3′,4′,5′-trimethoxybenzoyl)benzo[b]furan molecular scaffold was synthesized and evaluated for in vivo and in vitro biological activity. These derivatives were synthesized with different electron-releasing or electron-withdrawing substituents at one of the C-4 through C-7 positions. Methoxy substitution and location on the benzene part of the benzo[b]furan ring played an important role in affecting antiproliferative activity, with the greatest activity occurring with the methoxy group at the C-6 position, the least with the substituent at C-4. The same effect was also observed with ethoxy, methyl or bromine at the C-6 position of the benzo[b]furan skeleton, with the 6-ethoxy-2-amino-3-(3′,4′,5′-trimethoxybenzoyl)benzo[b]furan derivative 4f as the most promising compound of the series. This compound showed remarkable antiproliferative activity (IC50: 5 pM) against the Daoy medulloblastoma cell line, and 4f was nearly devoid of toxicity on healthy human lymphocytes and astrocytes. The potent antiproliferative activity of 4f was derived from its inhibition of tubulin polymerization by binding to the colchicine site. The compound was also examined for in vivo activity, showing higher potency at 15 mg/kg compared with the reference compound combretastatin A-4 phosphate at 30 mg/kg against a syngeneic murine mammary tumor.

Synthesis and Herbicidal Activity of Trifluoromethyl‐Substituted Phenyl Alkyl Ketoxime Esters of Bispyribac

AbstractA series of new trifluoromethyl‐substituted phenyl alkyl ketoxime esters of Bispyribac were synthesized as potential herbicides. All synthesized compounds were characterized by nuclear magnetic resonance (NMR) spectroscopy and high‐resolution mass spectrometry (HRMS). Sprout method and foliar spray method were used to study the herbicidal activity of the synthesized compounds. Among all synthesized compounds, compound 3 (4‐trifluoromethylphenyl n‐butyl ketoxime ester of Bispyribac) exhibits the highest herbicidal activity against Echinochloa crusgalli (L.) Beauv with median effect dose (ED50) of 1.7 μg/mL in pre‐emergence herbicidal activity study. The structure‐activity relationship analysis indicates that trifluoromethyl substitution on the phenyl group exhibits better activity than methoxy and methyl substitution on the phenyl group. The alkyl chain length also affects the activity significantly and the optimal alkyl chain length is four among the tested compounds. However, the substitution position of trifluoromethyl exhibits very limited influence on the activity. In post‐emergence herbicidal activity study, compound 3 (ED90 69.1056 g/hm2) exhibits better herbicidal activity against Echinochloa crusgalli (L.) Beauv than Pyribenzoxim (ED90 99.0810 g/hm2). Moreover, compound 3 exhibits better safety to hybrid rice variety II you 084 and rice variety Nanjing 44 than Pyribenzoxim in crop safety study. Compound 3 may serve as a lead compound for future herbicide discovery.

Solution processed deep blue thermally activated delayed fluorescent emitters using a solubility enhancing acceptor

A blue solution type organic light-emitting diode was developed by designing a thermally activated delayed fluorescent emitter with tert-butylcarbazole donors and a methoxy substituted phenyltriazine acceptor. The methoxy substituted diphenyltriazine acceptor was adopted for both solubility through solubilizing effect of the methoxy unit and blue shifted emission color through electron donating character weakening the acceptor character of diphenyltriazine. The doping of the soluble blue emitter in the high triplet energy host provided high external quantum efficiency of 16.1% and blue color coordinate of (0.16, 0.20). The methoxy substitution in addition to the tert-butyl substitution enabled the high external quantum efficiency and deep blue color coordinate in the solution processed thermally activated delayed fluorescent devices.

Design, synthesis and biological evaluation of 2-alkoxycarbonyl-3-anilinoindoles as a new class of potent inhibitors of tubulin polymerization.

A new class of inhibitors of tubulin polymerization based on the 2-alkoxycarbonyl-3-(3',4',5'-trimethoxyanilino)indole molecular skeleton was synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization and cell cycle effects. The results presented show that the methoxy substitution and location on the indole nucleus plays an important role in inhibition of cell growth, and the most favorable position for the substituent was at C-6. In addition, a small-size ester function (methoxy/ethoxycarbonyl) at the 2-position of the indole core was desirable. Also, analogues that were alkylated with methyl, ethyl or n-propyl groups or had a benzyl moiety on the N-1 indolic nitrogen retained activity equivalent to those observed in the parent N-1H analogues. The most promising compounds of the series were 2-methoxycarbonyl-3-(3',4'.5'-trimethoxyanilino)-5-methoxyindole 3f and 1-methyl-2-methoxycarbonyl-3-(3',4'.5'-trimethoxyanilino)-6-methoxy-indole 3w, both of which target tubulin at the colchicine site with antitubulin activities comparable to that of the reference compound combretastatin A-4.

Design, Synthesis, and Biological Evaluation of 2-(2-Bromo-3-nitrophenyl)-5-phenyl-1,3,4-oxadiazole Derivatives as Possible Anti-Breast Cancer Agents.

Breast Cancer (BCa) is the most often diagnosed cancer among women who were in the late 1940's. Breast cancer growth is largely dependent on the expression of estrogen and progesterone receptor. Breast cancer cells may have one, both, or none of these receptors. The treatment for breast cancer may involve surgery, hormonal therapy (Tamoxifen, an aromatase inhibitor, etc.) and oral chemotherapeutic drugs. The molecular docking technique reported the findings on the potential binding modes of the 2-(2-bromo-3-nitrophenyl)-5-phenyl-1,3,4-oxadiazole derivatives with the estrogen receptor (PDB ID: 3ERT). The 1,3,4-oxadiazole derivatives 4a-4j have been synthesized and described by spectroscopic method. 2-(2-Bromo-6-nitrophenyl)-5-(4-bromophenyl)-1,3,4-oxadiazole (4c) was reconfirmed by single-crystal XRD. All the compounds have been tested in combination with generic Imatinib pharmaceutical drug against breast cancer cell lines isolated from Caucasian woman MCF-7, MDA-MB-453 and MCF-10A non-cancer cell lines. The compounds with the methoxy (in 4c) and methyl (in 4j) substitution were shown to have significant cytotoxicity, with 4c showing dose-dependent activation and decreased cell viability. The mechanism of action was reported by induced apoptosis and tested by a DNA enzyme inhibitor experiment (ELISA) for Methyl Transferase. Molecular dynamics simulations were made for hit molecule 4c to study the stability and interaction of the protein-ligand complex. The toxicity properties of ADME were calculated for all the compounds. All these results provide essential information for further clinical trials.

Design, Synthesis and In vitro Biological Activity of Some New 1,3- thiazolidine-4-one Derivatives as Chemotherapeutic Agents using Virtual Screening Strategies

Designing of a new series of derivatives possessing thiazolidine-4-one moiety, their virtual screening using various computational tools, synthesis of prioritized compounds, spectral characterization and biological evaluation along with the comparison of in silico & in vitro results. WHO has come up with a list of antibiotic-resistant "priority pathogens" i.e. families of bacteria, that pose the greatest threat to human health. Some virulent bacteria are focused in the present study namely Mycobacterium tuberculosis (multi drug resistant), Staphylococcus aureus (methicillin-resistant) Streptococcus pneumoniae, (penicillin-non-susceptible) and Pseudomonas aeruginosa (Carbapenem-resistant) One of the neglected pathogenic disease which needs an urgent attention is Leishmaniasis which has a major burden among the poorest segments of populations in Asia, Africa, and South America. 1. To design of a series of new heteroaryl-1,3-thiazolidin-4-one derivatives. 2. To prioritize the molecules for synthesis using virtual screening techniques. 3. To synthesize the virtually predicted molecules via different synthetic schemes. 4. To characterize the synthesized molecules by spectroscopic analysis. 5. To evaluate the synthesized compounds for in vitro biological activity. A series of new heteroaryl thiazolidine-4-one derivatives was designed and subjected to in silico prioritization using various virtual screening strategies. The prioritized thiazolidinone derivatives were synthesized and screened for their in vitro antitubercular, anticancer, antileishmanial and antibacterial (Staphylococcus aureus; Streptococcus pneumonia; Escherichia coli; Pseudomonas aeruginosa) activities. The compounds with electronegative substitutions exhibited positive antitubercular activity, the derivatives possessing a methyl substitution exhibited good inhibitory response against breast cancer cell line MCF-7 while the compounds possessing a hydrogen bond acceptor site like hydroxyl and methoxy substitution in their structures exhibited good in vitro antileishmanial activity. Some compounds exhibited potent activity against gram positive bacteria Pseudomonas aeruginosa as compared to the standards. The designed compounds exhibited good in vitro anti-infective potential which was in good agreement with the in silico predictions and they can be developed as important lead molecules for anti-infective and chemotherapeutic drug research.

Biferrocenyl Schiff bases as efficient corrosion inhibitors for an aluminium alloy in HCl solution: a combined experimental and theoretical study.

The corrosion inhibitive capabilities of some ferrocene-based Schiff bases on aluminium alloy AA2219-T6 in acidic medium were investigated using Tafel polarization, electrochemical impedance spectroscopy (EIS), weight loss measurement, FT-IR spectroscopy and scanning electron microscopic (SEM) techniques. The influence of molecular configuration on the corrosion inhibition behavior has been explored by quantum chemical calculation. Ferrocenyl Schiff bases 4,4′-((((ethane-1,2-diylbis(oxy))bis(4,1-phenylene))bis(methaneylylidene))bis(azaneylylidene))bisferrocene (Fcua), 4,4′-((((ethane-1,2-diylbis(oxy))bis(2-methoxy-1,4-phenylene))bis(methaneylylidene))bis(azaneylylidene))bisferrocene (Fcub) and 4,4′-((((ethane-1,2-diylbis(oxy))bis(2-ethoxy-1,4-phenylene))bis(methaneylylidene))bis(azaneylylidene))bisferrocene (Fcuc) have been synthesized and characterized by FT-IR, 1H and 13C NMR spectroscopic studies. These compounds showed a substantial corrosion inhibition against aluminium alloy in 0.1 M of HCl at 298 K. Fcub and Fcuc showed better anticorrosion efficiency as compared with Fcua due to the electron donating methoxy and ethoxy group substitutions, respectively. Polarization curves also indicated that the studied biferrocenyl Schiff bases were mixed type anticorrosive materials. The inhibition of the aluminium alloy surface by biferrocenyl Schiff bases was evidenced through scanning electron microscopy (SEM) studies. Semi-empirical quantum mechanical studies revealed a correlation between corrosion inhibition efficiency and structural functionalities.

Structural Study of Phenolic Acids by Triple Quadrupole Mass Spectrometry with Electrospray Ionization in Negative Mode and H/D Isotopic Exchange

This work reports the theoretical and experimental study of fragmentation reactions in the gas phase of five phenolic acids using triple quadrupole mass spectrometry by electrospray ionization in negative ionic mode, as well as the isotope exchange experiments. MS/MS spectra were analyzed to suggest the fragmentation mechanisms, while theoretical calculations at the theory level B3LYP/6-311+G** were performed to expose the proposed mechanisms viability for this class of compounds. As expected, compounds with aromatic methoxy substitution presented •CH3 radical elimination as the principal fragmentation pathway, forming dystonic ions. Compounds without methoxy substituents dissociate with higher energies losing the CO2, CO and H2O. The isotopic marking experiments indicated the exchange of hydrogens by deuterases in the hydroxyl protons, which corroborates with the proposed mechanisms.

The discovery of novel indazole derivatives as tubulin colchicine site binding agents that displayed potent antitumor activity both in vitro and in vivo

Tubulin inhibitors that bind to the colchicine site are widely studied anticancer agents. In continuous our researches, we designed a series of novel indazole derivatives as microtubule-targeting agents (MTAs). The structure-activity relationships (SARs) investigations indicated that a 3,4,5-trimethoxyphenyl moiety and a methyl or methoxy substitution were preferred for the better antiproliferative activity. The indazole derivatives 3c and 3f showed noteworthy low nanomolar potency against HepG2, HCT116, SW620, HT29 and A549 tumor cells. In mechanism studies, 3c and 3f were proved to target the colchicine site, inhibited tubulin polymerization and disrupted cellular microtubule networks, arrested HCT116 cell in G2/M phase and induced cell apoptosis. In the HCT116 xenografts mouse model, 3c and 3f suppressed tumor growth by 45.3% and 58.9% at an orally dose of 25 mg/kg without causing obvious weight loss. The indazole 3f may serve as a good lead or drug candidate for colorectal cancer therapy.