Experimental pharmacological research regarding some newly synthesized benzamides on central nervous system functions

Three newly synthesized benzamides by the Department of Pharmaceutical Chemistry of the Faculty of pharmacy from the University of Medicine and Pharmacy „Carol Davila” Bucharest were tested in order to determine whether these new molecules have similar effects on the central nervous system as those already in therapeutic use belonging to the same chemical group, such as tiapride (neuroleptic) or lidocaine (local anaesthetic). Tests were carried out on NMRI mice which were given new compounds, conventionally named I5C, I14C, and II5C in a dose of 1/20 of the lethal dose 50% (LD50), as previously determined. They received this treatment daily for 21 days. The evasive–investigating capacity of mice was determined using the platform test, and the motor activity using an Activity cage device. The results have shown that compounds I5C and II5C decrease the investigation capacity of the mice; and compound I5C inhibits motor activity, while II5C stimulates it. Thus we concluded that only compounds I5C and II5C have a neuroleptic potential that might be investigated further

Experimental pharmacological research regarding some new quinazolin-4-ones derivatives

A series of new compounds with quinazolin-4-one structure, synthesized by the Pharmaceutical Chemistry Department of the Faculty of Pharmacy of the University of Medicine and Pharmacy “Carol Davila” Bucharest, was studied. Five of them were selected, conventionally named S1, S2, S3, S4, S5, and investigated in terms of their potential influence on the central nervous system (CNS). For this purpose, the antidepressant effect was determined using the forced swimming test; the anxiolytic/ anxiogenic effect was determined using the suspended plus-shaped maze (Ugo Basile); the effect on the motor activity was determined using the Ugo Basile activity cage; and the potential analgesic effect was investigated using the hot plate test (Ugo Basile). Compounds S3 and S5 lowered the motor activity and showed an anxiolytic effect, while S1 and S2 proved to have antidepressant and analgesic effects. A good correlation between antidepressant and analgesic effects was observed, consistent with the fact that analgesic drugs, by increasing norepinephrine and serotonin levels in the pain inhibiting descendent pathways, can be used as co-analgesics in therapy

Experimental pharmacological research regarding the antidepressant effect of associating doxepin and selegiline in normal mice

The severity and complexity of depression can vary widely among individuals, thus making single drug therapy ineffective in some cases. Taking this fact into account and using a mouse model, we set on investigating the possibility of obtaining a synergism of action between a classical tricyclic antidepressant that inhibits noradrenalin and serotonin reuptake (doxepin), and a modern antidepressant that inhibits type-B monoamine oxidase (selegiline). We measured the antidepressant effect using the forced swimming test and the tail suspension test. We determined motor activity using the Activity Cage test. Our results have shown that the antidepressant effect intensifies significantly in the animals treated with both antidepressants simultaneously compared to those treated only with doxepin. Furthermore, we observed that selegiline decreases the sedative effect of doxepin in the Activity Cage test

Respiratory burst oxidase-D Expression and Biochemical Responses in Festuca arundinacea under Drought Stress

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases catalyze the production of superoxide, a type of reactive oxygen species (ROS). In plants, the NADPH oxidase homologs have been identified as respiratory burst oxidase homologs (Rboh). They are involved in ROS production in response to drought stress. Three entries of tall fescue (Festuca arundinacea Schreb.) were used for analyses in the present study: tolerant (‘Isfahan’) and sensitive (‘Quchan’) accessions to drought during the germination stage, selected from 14 wild populations in Iran, as well as ‘Barvado’ as a control. Partial sequence of the Festuca respiratory burst oxidase-D (FrbohD) gene was isolated from Barvado. We compared expression levels of the FrbohD gene as well as hydrogen peroxide (H2O2), catalase activity and some biochemical responses among the three entries. Gene expression was evaluated for leaf and shoot samples subjected to 3, 6, and 9 d without water. The transcript level of FrbohD, H2O2 content, and catalase activity increased in Quchan under drought stress. It appears that lower levels of FrbohD gene transcription and H2O2 concentration in F. arundinacea leaves contributed to drought stress tolerance in Isfahan. Total protein and total soluble carbohydrate content also increased significantly in Isfahan when it was subjected to drought stress. Isfahan exhibited drought resistance through various strategies, which could serve as selection criteria for improving drought resistance in turfgrass breeding programs

Design, Synthesis and In Vitro Characterization of Novel Antimicrobial Agents Based on 6-Chloro-9H-carbazol Derivatives and 1,3,4-Oxadiazole Scaffolds

In this paper, we aimed to exploit and combine in the same molecule the carbazole and the 1,3,4-oxadiazole pharmacophores, to obtain novel carprofen derivatives, by using two synthesis pathways. For the first route, the following steps have been followed: (i) (RS)-2-(6-chloro-9H-carbazol-2-yl)propanonic acid (carprofen) treatment with methanol, yielding methyl (RS)-2-(6-chloro-9H-carbazol-2-yl)propanoate; (ii) the resulted methylic ester was converted to (RS)-2-(6-chloro-9H-carbazol-2-yl)propane hydrazide (carprofen hydrazide) by treatment with hydrazine hydrate; (iii) reaction of the hydrazide derivative with acyl chlorides led to N-[(2RS)-2-(6-chloro-9H-carbazol-2-yl)propanoil]-N′-R-substituted-benzoylhydrazine formation, which; (iv) in reaction with phosphorus oxychloride gave the (RS)-1-(6-chloro-9H-carbazol-2-yl)-1-(1,3,4-oxadiazol-2-yl)ethane derivatives. In the second synthesis pathway, new 1,3,4-oxadiazole ring compounds were obtained starting from carprofen which was reacted with isoniazid, in the presence of phosphorus oxychloride to form (RS)-1-(6-chloro-9H-carbazol-2-yl)-1-[5-(4-pyridyl)-1,3,4-oxadiazol-2-yl]ethane. The synthesized compounds were characterized by IR, 1H-NMR and 13C-NMR, screened for their drug-like properties and evaluated for in vitro cytotoxicity and antimicrobial activity. The obtained compounds exhibited a good antimicrobial activity, some of the compounds being particularly active on E. coli, while others on C. albicans. The most significant result is represented by their exceptional anti-biofilm activity, particularly against the P. aeruginosa biofilm. The cytotoxicity assay revealed that at concentrations lower than 100 μg/mL, the tested compounds do not induce cytotoxicity and do not alter the mammalian cell cycle. The new synthesized compounds show good drug-like properties. The ADME-Tox profiles indicate a good oral absorption and average permeability through the blood brain barrier. However, further research is needed to reduce the predicted mutagenic potential and the hepatotoxicity