Antinociceptive and anxiolytic-like effects of some compounds carrying benzothiazole ring

Bu çalışmanın amacı benzotiyazol halkası taşıyan bazı bileşiklerin antinosiseptif ve anksiyolitik-benzeri etkilerinin incelenmesidir. 40 mg/kg dozda uygulanan test bileşiklerinin antinosiseptif etkileri kuyruk sıkıştırma, sıcak plaka ve asetik asid ile indüklenen kıvranma testleri ile araştırılmıştır. Bileşiklerin anksiyolitik-benzeri etkilerini incelemek için delikli tahta ve yükseltilmiş artı labirent testleri gerçekleştirilmiştir. Farelerin motor koordinasyonlarını değerlendirmek üzere Rota-rod cihazı kullanılmıştır. Deneyler sonucunda 3f, 3g ve 3h kodlu bileşiklerin kuyruk sıkıştırma ve sıcak plaka testlerinde hayvanların reaksiyon sürelerini artırdığı ve 3e kodlu bileşiğin ise asetik asid ile indüklenen kıvranma testinde farelerin kıvranma sayılarını azalttığı belirlenmiştir. Diğer yandan, 3f, 3g ve 3h kodlu bileşikler delikli tahta testinde farelerin ilk baş daldırma sürelerini kısaltırken toplam baş daldırma sayılarını artırmıştır. Yükseltilmiş artı labirent testinde ise aynı türevlerin farelerin açık kola giriş sayılarının ve açık kolda kalma sürelerinin yüzdelerini artırdığı ortaya konulmuştur. Rota-rod testlerinde test bileşikleri farelerin dönen milden düşme sürelerini değiştirmemiştir. Tüm bu bulgular, 3f, 3g ve 3h kodlu bileşiklerin santral antinosiseptif ve anksiyolitik-benzeri etki gösterdiklerine; 3e kodlu bileşiğin ise periferal antinosiseptif etki gösterdiğine işaret etmektedir.The aim of this study was to examine the antinociceptive and anxiolytic-like effects of some compounds carrying benzothiazole ring. The antinociceptive effects of test compounds, administrated at a dose of 40 mg/kg, were investigated by tail clip, hot plate and acetic acid-induced writhing tests. Hole board and elevated plus maze tests were performed to evaluate the anxiolytic-like effects of the compounds. Rota-rod device was used to assess the motor coordinations of mice. As a result of the experiments, it was determined that compounds 3f, 3g and 3h increased the reaction times of animals in the tail clip and hot plate tests, and compound 3e reduced the writhing number of mice in the acetic acid-induced writhing test. On the other hand, in the hole board test, compounds 3f, 3g and 3h reduced the first head-dipping latencies of mice while increasing the total number of head-dips. In the elevated plus maze test, it has been shown that the same derivatives increase the percentages of open arm entries and time spent in the open arms. In the Rota-rod tests, test compounds did not change the falling time of mice from the rotating mill. All these findings point out that compounds 3f, 3g and 3h exhibit central antinociceptive and anxiolytic-like effects and compound 3e shows a peripheral antinociceptive effect

Synthesis and Antidepressant Activity Profile of Some Novel Benzothiazole Derivatives

Within the scope of our new antidepressant drug development efforts, in this study, we synthesized eight novel benzothiazole derivatives 3a–3h. The chemical structures of the synthesized compounds were elucidated by spectroscopic methods. Test compounds were administered orally at a dose of 40 mg/kg to mice 24, 5 and 1 h before performing tail suspension, modified forced swimming, and activity cage tests. The obtained results showed that compounds 3c, 3d, 3f–3h reduced the immobility time of mice as assessed in the tail suspension test. Moreover, in the modified forced swimming tests, the same compounds significantly decreased the immobility, but increased the swimming frequencies of mice, without any alteration in the climbing frequencies. These results, similar to the results induced by the reference drug fluoxetine (20 mg/kg, po), indicated the antidepressant-like activities of the compounds 3c, 3d, 3f–3h. Owing to the fact that test compounds did not induce any significant alteration in the total number of spontaneous locomotor activities, the antidepressant-like effects of these derivatives seemed to be specific. In order to predict ADME parameters of the synthesized compounds 3a–3h, some physicochemical parameters were calculated. The ADME prediction study revealed that all synthesized compounds may possess good pharmacokinetic profiles

Synthesis and Biological Evaluation of Some Novel Dithiocarbamate Derivatives

18 novel dithiocarbamate derivatives were synthesized in order to investigate their inhibitory potency on acetylcholinesterase enzyme and antimicrobial activity. Structures of the synthesized compounds were elucidated by spectral data and elemental analyses. The synthesized compounds showed low enzyme inhibitory activity. However, they displayed good antimicrobial activity profile. Antibacterial activity of compounds 4a, 4e, and 4p (MIC = 25 μg/mL) was equal to that of chloramphenicol against Klebsiella pneumoniae (ATCC 700603) and Escherichia coli (ATCC 35218). Most of the compounds exhibited notable antifungal activity against Candida albicans (ATCC 10231), Candida glabrata (ATCC 90030), Candida krusei (ATCC 6258), and Candida parapsilosis (ATCC 7330). Moreover, compound 4a, which carries piperidin-1-yl substituent and dimethylthiocarbamoyl side chain as variable group, showed twofold better anticandidal effect against all Candida species than reference drug ketoconazole

Synthesis and Evaluation of New 1,3,4-Thiadiazole Derivatives as Antinociceptive Agents

In the current work, new 1,3,4-thiadiazole derivatives were synthesized and investigated for their antinociceptive effects on nociceptive pathways of nervous system. The effects of these compounds against mechanical, thermal and chemical stimuli were evaluated by tail-clip, hot-plate and acetic acid-induced writhing tests, respectively. In addition, activity cage was performed to assess the locomotor activity of animals. The obtained data indicated that compounds 3b, 3c, 3d, 3e, 3g and 3h increased the reaction times of mice both in the hot-plate and tail-clip tests, indicating the centrally mediated antinociceptive activity of these compounds. Additionally, the number of writhing behavior was significantly decreased by the administration of compounds 3a, 3c, 3e and 3f, which pointed out the peripherally mediated antinociceptive activity induced by these four compounds. According to the activity cage tests, compounds 3a, 3c and 3f significantly decreased both horizontal and vertical locomotor activity of mice. Antinociceptive behavior of these three compounds may be non-specific and caused by possible sedative effect or motor impairments

Synthesis of Some Novel Thiadiazole Derivative Compounds and Screening Their Antidepressant-Like Activities

Novel thiadiazole derivatives were synthesized through the reaction of acetylated 2-aminothiadiazole and piperazine derivatives. The chemical structures of the compounds were clarified by Infrared Spectroscopy (IR), 1H Nuclear Magnetic Resonance Spectroscopy (1H-NMR), 13C Nuclear Magnetic Resonance Spectroscopy (13C-NMR) and Electronspray Ionisation Mass Spectroscopy (ESI-MS) spectroscopic methods. Antidepressant-like activities were evaluated by the tail-suspension (TST) and modified forced swimming (MFST) methods. Besides, possible influence of the test compounds on motor activities of the animals were examined by activity cage tests. In the TST, administration of the compounds 2c, 2d, 2e, 2f, 2g and 2h significantly decreased the immobility time of mice regarding the control values. Further, in the MFST, the same compounds reduced the total number of immobility behaviors while increasing swimming performance. However, no change was observed in the total number of climbing behaviors. These data suggested that compounds 2c, 2d, 2e, 2f, 2g and 2h possess notable antidepressant-like activities. Reference drug fluoxetine (10 mg/kg) was also exhibited its antidepressant activity, as expected. No significant difference was seen between the locomotor activity values of the test groups signifying that observed antidepressant-like activities are specific. Theoretical calculation of absorption, distribution, metabolism, excretion (ADME) properties for the obtained compounds were performed and obtained data supported the antidepressant-like potential of these novel thiadiazole derivatives

The Effect of Agomelatine Treatment on Diabetes-Induced Cognitive Impairments in Rats: Concomitant Alterations in the Hippocampal Neuron Numbers

Researches that are related to the central nervous system complications of diabetes have indicated higher incidence of cognitive disorders in patients. Since the variety of nootropic drugs used in clinics is limited and none of them consistently improves the outcomes, new and effective drug alternatives are needed for the treatment of diabetes-induced cognitive disorders. Based on the nootropic potential of agomelatine, the promising efficacy of this drug on cognitive impairments of diabetic rats was investigated in the current study. Experimental diabetes model was induced by streptozotocin. After development of diabetes-related cognitive impairments in rats, agomelatine (40 and 80 mg/kg) was administrated orally for two weeks. Cognitive performance was assessed by Morris water-maze and passive avoidance tests. Then, the total numbers of neurons in both dentate gyrus and Cornu Ammonis (CA) 1–3 subfields of the hippocampus were estimated by the optical fractionator method. Agomelatine treatment induced notable enhancement in the learning and memory performance of diabetic rats. Moreover, it reversed the neuronal loss in the hippocampal subregions of diabetic animals. Obtained results suggest that agomelatine has a significant potential for the treatment of diabetes-induced cognitive impairments. However, therapeutic efficacy of this drug in diabetic patients suffering from cognitive dysfunctions needs to be confirmed by further clinical trials

Catecholaminergic and Cholinergic Systems Mediate Beneficial Effect of Vortioxetine on Diabetes-Induced Neuropathic Pain

The therapeutic potential of vortioxetine on mechanical hyperalgesia/allodynia was investigated in rats with streptozotocin-induced diabetes, and its possible mechanism of action was elucidated in this study. The obtained findings demonstrated that subacute vortioxetine treatment (5 and 10 mg/kg for 2 weeks) increased the reduced paw-withdrawal thresholds of diabetic rats both in the Randall–Selitto and Dynamic plantar tests. Moreover, the falling latencies of animals did not change in the Rota-rod assessments. These results suggest that vortioxetine administration significantly improved diabetes-induced hyperalgesia and allodynia responses in the rats without affecting their motor coordination. The vortioxetine (5 mg/kg)-induced antihyperalgesic and antiallodynic effects were reversed by AMPT, yohimbine, ICI 118,551, sulpiride and atropine pre-treatments, suggesting the involvement of the catecholaminergic system, α2- and β2-adrenoceptors, D2/3 dopaminergic receptors and cholinergic muscarinic receptors in the exhibited pharmacological activity, respectively. Moreover, the data from the immunohistochemical studies indicated that the inhibition of c-Fos overexpression in dorsal horn neurons also mediates the beneficial effect of this drug. Vortioxetine induced no difference in plasma glucose levels in diabetic rats. If clinical studies confirm these findings, the concomitant beneficial effect of vortioxetine on mood disorders and its neutral activity profile on glycemic control may make it an alternative drug for the treatment of neuropathic pain

Pharmacological and Toxicological Screening of Novel Benzimidazole-Morpholine Derivatives as Dual-Acting Inhibitors

The aim of this study was to investigate acetylcholinesterase (AChE), monoamine oxidase A (MAO-A), monoamine oxidase B (MAO-B), cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzyme inhibitory, and antimicrobial activities of a new series of 2-(4-substituted phenyl)-1-[2-(morpholin-4-yl)ethyl]-1H-benzimidazole derivatives, for their possible use as multi-action therapeutic agents. Target compounds (n = 15) were synthesized under microwave irradiation conditions in two steps, and their structures were elucidated by FT-IR, 1H-NMR, 13C-NMR and high resolution mass spectroscopic analyses. Pharmacological screening studies revealed that two of the compounds (2b and 2j) have inhibitory potential on both COX-1 and COX-2 enzymes. In addition, cytotoxic and genotoxic properties of the compounds 2b, 2j and 2m were investigated via the well-known MTT and Ames tests, which revealed that the mentioned compounds are non-cytotoxic and non-genotoxic. As a concise conclusion, two novel compounds were characterized as potential candidates for treatment of frequently encountered inflammatory diseases

Anticholinesterase activity screening of some novel dithiocarbamate derivatives including piperidine and piperazine moieties

<p>The present study was undertaken to synthesize some novel lipophilic piperazine and piperidinedithiocarbamates and investigate their inhibitory potencies against cholinesterase enzymes. In the synthetic studies, 44 new compounds were isolated. The structures of the synthesized compounds were confirmed by spectroscopic analyses. Enzymatic studies were carried out using modified Ellman's assay against Acetylcholinesterase (AChE) and Butrylcholinesterase (BChE) enzymes, and it was observed that some of the compounds selectively inhibit AChE. Theoretical ADME predictions were calculated for selected compounds in the series. Enzyme kinetics and molecular docking studies were performed for the most active compound C41 and nature of inhibition and interactions between enzyme and ligand were explained.</p