Synthesis Of Some 2,3-Dihydro-1,3,4-Oxadiazoles And 4,5-Dihydro-1,2,4-Triazoles As Anticancer Agents

Objective: The main objective of this work was to synthesize and evaluate the novel 2,3-dihydro-1,3,4-oxadiazole and 4,5-dihydro-1,2,4-triazole derivatives for cytotoxic activities. Methods: The 2,3-dihydro-1,3,4-oxadiazole derivatives 4a-h were synthesized by cyclization of N'-(substituted-benzylidene) isonicotinohydrazide 3a-e in refluxing acetic anhydride. The 2,3-dihydro-1,3,4-oxadiazole derivatives 4a-h were converted into the corresponding 4,5-dihydro-1,2,4-triazoles 5a-h using ammonia. All the synthesized compounds were identified, depending on the physical and spectral data. Title compounds were assessed for their cytotoxic activity against human cancer cell line (MCF-7) by using Sulforhodamine B (SRB) colorimetric assay. Results: All the synthesized compounds showed characteristic peaks in FTIR, 1HNMR and Mass spectral analysis. The results of the in vitro cytotoxic activity revealed that the compound 4c exhibited equipotent cytotoxic activity with an IC50 value of 8.04 µM when compared with that of standard drug doxorubicin (IC50= 8.02 µM). The reminder compounds have shown good to moderate cytotoxic activities when compared with that of a reference standard. Conclusion: We synthesized a series of title compounds in quantitative yields. Most derivatives showed moderate to good cytotoxic activity.

Evaluation as antioxidant agents of 1,2,4-triazole derivatives: effects of essential functional groups.

A series of 1,2,4-triazole derivative compounds substituted with groups of phenol and pyridine were synthesized in high yields and screened against several antioxidant activity parameters such as DPPH, ABTS, metal chelating, reducing power and the total antioxidant activity. The compounds showed better than expected antioxidant activity between the studied biological activity parameters. Among these, compound G(2-(5- mercapto-4H-1,2,4-triazol-3-yl)phenol) had a high total antioxidant activity potential with value of 232.12±6.89 mmol/ml. Also showed fairly good ABTS cation radical and DPPH radical scavenging activity with values of IC50 = 4.59±4.19 and IC50 = 7.12±2.32μg/mL respectively. Further, the antioxidant potential of heterocyclic compounds that 1,2,4-triazole derivatives containing different functional groups were compared with various tests performed and has been shown to increase the activity of electron donating groups. Therefore, the present study demonstrates that phenol and pyridine substituted 1,2,4-triazole compounds would be a better prospective in the development of antioxidant agent.

Antioxidant effects of methylprednisolone and hydrocortisone on the impairment of endothelium dependent relaxation induced by reactive oxygen species in rabbit abdominal aorta / 대한마취과학회지

BACKGROUND: The reperfusion following ischemia produces reactive oxygen species (ROS). We studied the influences of methylprednisolone (MPD) and hydrocortisone (CRT) on ROS effects using the endothelium of rabbit abdominal aorta. METHODS: Isolated rabbit aortic rings were suspended in an organ bath filled with Krebs-Henseleit (K-H) solution. After precontraction with norepinephrine, changes in arterial tension were recorded following the cumulative administration of acetylcholine (ACh). The percentages of ACh-induced relaxation of aortic rings before and after exposure to ROS, generated by electrolysis of K-H solution, were used as the control and experimental values, respectively. The aortic rings were pretreated with MPD or CRT at the same concentrations, and the effects of these agents were compared with the effects of ROS scavenger inhibitors: superoxide dismutase inhibitor, diethylthiocarbamate (DETCA), and the catalase inhibitor, 3-amino-1,2,4-triazole (3AT). RESULTS: Both MPD and CRT maintained endothelium-dependent relaxation induced by ACh in a dose-related manner in spite of ROS attack. The restored ACh-induced relaxation of MPD and CRT group was not attenuated by pretreatment of 3AT and DETCA. CONCLUSIONS: MPD and CRT preserve the endothelium-dependent vasorelaxation against the attack of ROS, in a dose-related manner. Endothelial protection mechanisms of MPD and CRT may be not associated with hydrogen peroxide and superoxide scavenging.

Antioxidant effect of lidocaine and procaine on reactive oxygen species-induced endothelial dysfunction in the rabbit abdominal aorta / 대한마취과학회지

BACKGROUND: Reactive oxygen species (ROS) induce lipid peroxidation and tissue damage in the endothelium. We tested the antioxidant effect of lidocaine and procaine on ROS-induced endothelial damage in the rabbit aorta. METHODS: Aortic rings isolated from rabbits were suspended in an organ bath filled with Krebs-Henseleit (K-H) solution bubbled with 5% CO2 and 95% O2 at 37.5degrees C. After precontraction with phenylephrine (PE, 10(-6) M), changes in tension were recorded following a cumulative administration of acetylcholine (ACh 3 x 10(-8) to 10(-6) M). Differences were measured as percentages of ACh-induced relaxation of aortic rings before and after exposure to ROS as generated by electrolysis of the K-H solution. The aortic rings were pretreated with lidocaine or procaine (10(-5) M to 3 x 10(-3) M) to compare their effects, as well as ROS scavengers, catalase, mannitol, sodium salicylate, and deferoxamine, and a catalase inhibitor, 3-amino-1,2,4-triazole (3AT). RESULTS: Lidocaine and procaine dose-dependently maintained endothelium-dependent relaxation induced by ACh despite ROS activity (P < 0.05 vs control value). The 3AT pretreated procaine (3 x 10(-3) M) group decreased more significantly than the un-pretreated procaine group (P < 0.05). CONCLUSIONS: These findings suggest that lidocaine and procaine dose-dependently preserve endothelium-dependent vasorelaxation against ROS attack, potentially via hydrogen peroxide scavenging.

Spectrophotometric determination of chondroitin sulfate with 4-amino-3-hydrazine-5-mercapto-1,2,4-triazole / 中国海洋药物

To establish a new method for the determination of chondroitin sulfate. The method was based on the interaction of sodium chondroitin sulfate with 4-amino-3-hydrazino-5-mercapto-1,2,4-triazole to yield a violet product, 6-mercapto-3-substituted-s-triazolo-\[4,3-b\]-s-tetrzaine derivatives. Absorbance at 540 nm obeyed Beer's Law within the concentration range from 0.1 to 1.0 g?L~(-1)and the results were precise and accurate. The method was operationally simple and had a good precision and sensitivity.