Oxidative stress responses of juvenile tambaqui Colossoma macropomum after short-term anesthesia with benzocaine and MS-222

ABSTRACT The present study aimed to evaluate the effects of benzocaine and tricaine methanesulfonate on oxidative stress parameters of juvenile tambaqui tissues. Fish (n=80) were anesthetized with benzocaine (100 mg L-1) or tricaine (240 mg L-1) and two control groups were used (non-anesthetized fish and fish exposed to ethanol-only). After anesthetic induction 10 fish/anesthetic were euthanized after 3, 12 and 24 hours post-anesthesia and tissue samplings (gills, liver and brain) were performed. Samples were submitted to analyses of enzyme activity glutathione-S-transferase (GST), cellular lipid peroxidation (TBARS) and total antioxidant capacity (ACAP). ACAP increased in gills of benzocaine treatment after 12 hours. The liver showed a reduction in ACAP of tricaine treatment after 12 hours. Both anesthetic treatments showed an increase of ACAP at 24 hours compared to control group. The activity of the GST enzyme increased in the gills for treatments benzocaine and tricaine after 3 and 12 hours. Liver showed increased GST activity (benzocaine after 24 hours and tricaine after 3 and 24 hours). Lipid damage decreased in gills (both anesthetics) and brain (tricaine) after 24 hours. The results demonstrate that benzocaine and tricaine did not cause oxidative damage in juvenile tambaqui under the experimental conditions herein established.

Design of next generation antibody drug conjugates / 药学学报

Chemotherapy remains one of the major tools, along with surgery, radiotherapy, and more recently targeted therapy, in the war against cancer. There have appeared a plethora of highly potent cytotoxic drugs but the poor discriminability between cancerous and healthy cells of these agents limits their broader application in clinical settings. Therapeutic antibodies have emerged as an important class of biological anticancer agents, thanks to their ability in specific binding to tumor-associated antigens. While this important class of biologics can be used as single agents for the treatment of cancer through antibody-dependent cell cytotoxicity (ADCC), their therapeutical efficacy is often limited. Antitumor antibody drug conjugates (ADCs) combine the target-specificity of monoclonal antibody (mAb) and the highly active cell-killing drugs, taking advantages of the best characteristics out of both components. Thus, insufficiency of most naked mAbs in cancer therapy has been circumvented by arming the immunoglobulin with cytotoxic drugs. Here mAbs are used as vehicles to transport potent payloads to tumor cells. ADCs contain three main components: antibody, linker and cytotoxics (also frequently referred as payload). Antibodies can recognize and specifically bind to the tumor-specific antigens, leading to an antibody-assisted internalization, and payload release. While ADC has demonstrated tremendous success, a number of practical challenges limit the broader applications of this new class of anticancer therapy, including inefficient cellular uptake, low cytotoxicity, and off-target effects. This review article aims to cover recent advances in optimizing linkers with increased stability in circulation while allowing efficient payload release within tumor cells. We also attempt to provide some practical strategies in resolving the current challenges in this attractive research area, particularly to those new to the field.

Synthesis of 2-hydroxyl-5-butyramidobenzoic acid and its effect on acetic acid-induced colitis in rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the method for synthesis of 2-hydroxyl-5- butyramidobenzoic acid and test its effect on acetic acid-induced colitis in rats.</p><p><b>METHODS</b>2-hydroxyl-5-butyramidobenzoic acid was synthesized from 5-aminosalicylic acid and butyric acid by amidation, esterification and hydrolization. The effect of 2-hydroxyl-5-butyramidobenzoic acid on acetic acid enema-induced colitis in rats was investigated.</p><p><b>RESULTS</b>The structure of 2-hydroxyl-5-butyramidobenzoic acid was identified by IR and 1H-NMR. After treatment with acetic acid, the colon mucosal damage index (CMDI), fecal occult blood (OB) test, and activity of myelperoxidase (MPO) increased significantly in the rats as compared to the control levels. 2-hydroxyl-5- butyramidobenzoic acid obviously reduced the CMDI and OB, and reduced the level of MPO in the rats with colitis.</p><p><b>CONCLUSION</b>The synthesis of 2-hydroxyl-5-butyramidobenzoic acid requires only mild conditions with simple procedures, and the synthesized 2-hydroxyl-5-butyramidobenzoic acid shows obvious therapeutic effects on mucosal damage of in rats with acetic acid-induced colitis.</p>

Synthesis and antitumor activity of benzoic nitrogen mustard derivatives / 药学学报

To study the effect of isoprenoid and aliphatic saturated alcohols as modificator on benzoic nitrogen mustard, the intermediate 4-[N,N-bis(2-chloroethyl) amino] benzoic acid 4 was prepared in four steps utilizing p-amino benzoic acid as the starting material. Target compounds were synthesized by the catalytic esterification of DCC/DMAP and the structures of the six new esters were characterized by elemental analysis, 1H NMR, 13C NMR and MS. Antitumor activities were evaluated in vitro using MTT assay. The result showed that some derivatives were more potent than the intermediate 4, and compound 5c modified with dodecanol exhibited similar activity to the commercial drug melphalan.

Effect of aromatic hydrotropies on the solubility of carbamazepine part I: effect of sodium salt of hydroxy and amino derivatives of benzoic acid

It was found that the hydrotropic agents enhance the water-solubility of carbamazepine as a function of their concentration. The solubilizing power of these hydrotropes was shown to be highly dependent on their chemical structure. The solubilizing power of the amino derivatives is generally higher than that of the hydroxy derivatives. The position of the hydroxyl or amino groups relevant to the carboxylate group in the hydrotrope molecule plays a major role in its solubilizing effect. The spectral pattern of carbamazepine was found to undergo a change in presence of these compounds. Applying the continuous variation method revealed formation of 2:1 carbamazepine complex with each of sodium salicylate and sodium anthranilate as well as a 1:2 complex with sodium p-amino benzoate. Also, the drug forms 1:1 complexes with both sodium m-hydroxybenzoate and sodium p-hydroxybenzoate. On the other hand, two species of complexes appear to be formed in carbamazepine-sodium p- aminosalicylate system, viz., 1:2 and 2:1 complexes. An apparent correlation seems to exist between the solubilizing power of the investigated hydrotropes and the stability constant of their respective complexes with the drug. Calculating the amount of drug solubilized in free as well as in complexed forms in these systems revealed that the decrease in the activity coefficient of carbamazepine in presence of the investigated hydrotropes may be responsible for the increase in carbamazepine solubility beside complex-formation

Flourimetric and colorimetric determination of 1-amino-2-propanol, ethanolamine, benzocaine and 4-amino benzoic acid

A convenient and simple fluorimetric method for the determination of 1-amino-2-propanol, ethanolamine, benzocaine and 4-amino benzoic acid has been developed. The method depends on the reaction of the previously mentioned amines with m-hydroxy benzaldehyde to form highly fluorescent Schiff bases in absolute alcohol at 70C for 20 minutes. On the other hand, these primary amine-containing compounds were determined by colorimetric method. The Schiff bases obtained possess yellow with maximum absorption wave length range of 460-480 nm. Beer's law obeyed in the range of 0.1-5 mg/ml. The effect of pH, temperature, time and solvent of the reaction for both fluorimetric and colorimetric methods were studied and optimized

Spectroscopic studies of the arylidene derivatives of some aminobenzoic acids hydrazides

The electronic absorption spectra of the arylidene derivatives of m- and p-aminobenzoic hydrazides were investigated in organic solvents of varying polarities and buffer solutions of different pH values. The behavior in buffer solutions was utilized for the determination of the acid dissociation constant. The important bands in the IR-spectra of compounds as well as the main signals in the 1H-NMR spectra were assigned and discussed in relation to molecular structure

Synthesis and structural studies of some new oxovanadium [IV] complexes with ON donor schiff bases derived from 2-acetyl pyrole and o-and p-aminobenzoic acids

Coordination compounds of oxovanadium [IV] with various bases have been investigated extensively but those of the Schiff bases which are derived from heterocyclic glyoxalic aldehydes have drawn attention in recent years. In this paper we present spectroscopic and magnetic studies of new VO [IV] complexes of two ON donor Schiff bases formed by the condensation of 2-acetyl pyrrole with o- and p-aminobenzoic acids. Since the tetragonal distortion seems to be the dominant feature in the present complexes, various radial parameters have been evaluated