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In this study, we aimed to design and synthesize novel molecules carrying both the thiazole and piperazine rings in their structures and to investigate their antinociceptive activity. Targeted compounds were obtained by reacting thiosemicarbazide derivative and appropriate 2-bromoacetophenone in ethanol. The structures of the obtained compounds were determined using data from various spectroscopic methods (IR, 1H-NMR, 13C-NMR, and LCMSMS). Experimental data from in vivo tests showed that test compounds 3a–3c, 3f, and 3g (50 mg/kg) significantly prolonged reaction times of animals in tail-clip and hot-plate tests compared to the controls, indicating that these compounds possess centrally mediated antinociceptive activities. Furthermore, these compounds reduced the number of writhing behaviors in the acetic acid-induced writhing tests, showing that the compounds also possess peripheral antinociceptive activity. In the mechanistic studies, naloxone pre-treatments abolished the antinociceptive activities of compounds 3a–3c, 3f, and 3g, indicating that opioidergic mechanisms were involved in their antinociceptive effects. Molecular docking studies demonstrating significant interactions between the active compounds and µ- and δ-opioid receptor proteins supported the pharmacological findings. This study is the first showing that molecules designed to bear thiazole and piperazine moieties together on their structure exert centrally and peripherally mediated antinociceptive effects by activating the opioid system.

WOS: 000418498400031, PubMed ID: 29132093, Background: Acetylcholinesterase (AChE) inhibitors are frequently prescribed to mitigate the cognitive decline in Alzheimer's disease. Thus, we investigated the possible efficacy of the AChE inhibitor 2-[(6-Nitro-2-benzothiazolyl) amino]-2-oxoethyl4-[2-(N, N-dimethylamino) ethyl] piperazine-1 carbodithioate (BPCT) in a streptozotocin (STZ)-induced Alzheimer's disease model (SADM). Methods: First, we analyzed the molecular interaction of BPCT with AChE via a docking study. Then, the cognitive effects of BPCT (10 and 20 mg/kg) were evaluated in intracerebroventricular STZ- and vehicle-administered rats with the elevated plus maze (EPM), Morris water maze (MWM), and active avoidance (AA) tests. Locomotor activity was also assessed. Results: Docking analysis indicated significant binding of BPCT to the AChE active site. In behavioral tests, STZ administration impaired cognitive performance in SADM rats versus control rats. Treatment with donepezil or BPCT significantly decreased the prolonged 2nd retention transfer latency and 2nd retention latency time values of the SADM group in the EPM and MWM tests, respectively. Further, prolonged latency times were decreased and reduced frequency of avoidance events were increased in the AA test. Locomotor activity between groups was not different. Conclusion: BPCT appears to function as a central AChE inhibitor, and its improvement of deficits in SADM rats suggests that it has therapeutic potential in Alzheimer's disease., Anadolu University Research Foundation (Eskisehir, Turkey) [1105S084], The authors with to thank Assoc. Prof. Dr. Yusuf Ozkay for the synthesis of the test compounds. This work was financially supported by the Anadolu University Research Foundation (Eskisehir, Turkey), Project No. 1105S084.

WOS: 000459738800012, Background: Benzimidazole and piperidine rings are important pharmacophore groups for drug design studies. Objective: In this study, we aimed to investigate the antidepressant-like activity of some 2-(4- substituted-phenyl)-1-[2-(piperidin-1-yl)ethyl]-1H-benzimidazole derivatives. Methods: Tail-suspension Test (TST) and Modified Forced Swimming Tests (MFST) were used to assess antidepressant-like activities of the test compounds. Moreover, locomotor activity performances of the animals were evaluated by an activity cage device. Results: In the TST and MFST, compounds 2c-2h (10 mg/kg) and the reference drug fluoxetine (20 mg/kg) significantly reduced the immobility time of mice indicating the antidepressant-like activities of these compounds. Further, in MFST, the same compounds induced significant enhancement in the duration of active swimming behaviors without affecting the climbing performance of the animals. This prolongation in the swimming time, similar to fluoxetine, pointed out that antidepressant-like activity of the compounds 2c-2h might be related to the serotonergic rather than noradrenergic mechanisms. Besides, results of the activity cage tests demonstrated that none of the tested compounds caused an alteration in the locomotor activities of mice, signifying that antidepressant-like effects presented in this study were specific. Conclusion: In conclusion, results of this present study supported the previous papers reporting the therapeutic potential of compounds carrying benzimidazole and/or piperidine rings in their structure and emphasized, once again, the importance of these pharmacophore groups in drug design studies., Anadolu University Scientific Research Projects Commission [1606S567], This research was supported from the Anadolu University Scientific Research Projects Commission (Project No: 1606S567). Moreover, the authors thank to the Prof. Dr. Yusuf Ozkay for the synthesis of the test compounds.

WOS: 000451641900153, PubMed ID: 30400609, Novel benzazole derivative compounds 4a-4h were obtained by the reaction of corresponding 2-(benzazol-2-ylthio)acetohydrazide and appropriate 4-substituted benzaldehydes. The chemical structures of the synthesized compounds were elucidated by FT-IR, H-1-NMR, C-13-NMR and LCMS spectroscopic methods. Antidepressant-like effects of the compounds were evaluated by tail suspension test (TST) and modified forced swimming tests (MFST). Moreover, locomotor activities of the animals were assessed by an activity cage apparatus. In the series, compounds 4a, 4b, 4e and 4f (at 50 mg/kg) significantly decreased the immobility time of mice in both of the TST and MFST. The same compounds prolonged the swimming time of animals in MFST without any change in the climbing duration. These data indicated that compounds 4a, 4b, 4e and 4f possess significant antidepressant-like activities. Moreover, pre-treatments with p-chloro-phenylalanine methyl ester (an inhibitor of serotonin synthesis), NAN-190 (a 5-HT1A antagonist), ketanserin (a 5-HT2A/2C antagonist), and ondansetron (a 5-HT3 antagonist) reversed the exhibited pharmacological effects. Results of the mechanistic studies suggested the involvement of serotonergic system and contributions of 5-HT1A, 5-HT2A/2C and 5-HT3 receptors to the antidepressant-like effects of compounds 4a, 4b, 4e and 4f. Furthermore, unchanged locomotor activity of mice following the administrations of these four derivatives confirmed that the presented antidepressant-like effects are specific., Anadolu University Scientific Research Projects Commission [1805S189], This research was supported from the Anadolu University Scientific Research Projects Commission (Project No: 1805S189).

WOS: 000385057400006, PubMed ID: 27590609, Aims: This study was planned to examine the antinociceptive efficacy of agomelatine against acute mechanical, thermal, and chemical nociceptive stimuli, as well as to determine the opioid receptor subtypes mediating these effects. Main methods: Tail-clip, hot-plate, and acetic acid-induced writhing tests were performed to evaluate antinociceptive effect. Besides, possible effect of agomelatine on the motor coordination of animals was assessed with a Rota-rod test. Keyfindings: Agomelatine (40 mg/kg and 60 mg/kg) significantly prolonged the reaction time of mice in both the tail-clip and hot-plate tests, suggesting the antinociceptive activity is related to both spinal and supraspinal mechanisms. This drug also reduced the number of writhing behaviors indicating the presence of a peripherally mediated antinociceptive effect Rota-rod testing displayed no notable effect on the motor activity of the animal supporting the conclusion that the observed antinociceptive effect is specific. The agomelatine-induced antinociceptive activity abrogated following pretreatment with naloxone (a non-selective opioid receptor antagonist, 5.48 mg/kg, i.p.), which suggested the participation of opioid mechanisms to the antinociception. The possible contribution of mu, delta and kappa subtypes of opioid receptors to the anti-nociceptive effect were evaluated using naloxonazine (7 mg/kg, s.c.), naltrindole (0.99 mg/kg, i.p.), and nor-binaltorphimine (1.03 mg/kg, i.p.), respectively. Pretreatments using these antagonists abolished the antinociceptive activity of agomelatine in all of the nociceptive test paradigms used, which pointed out that mu, delta, and kappa opioid receptors participated to the action of agomelatine on pain. Significance: These results demonstrated the therapeutic potential of agomelatine in the treatment of pain disorders, Anadolu University Research Foundation (Eskisehir, Turkey) [1404S127], This work was financially supported by the Anadolu University Research Foundation (Eskisehir, Turkey), project no. 1404S127.

WOS: 000374883700008, This study was planned to investigate possible antinociceptive activity of 1,5-diaryl-3-[4-(methylsulfonyl) phenyl]-4,5-dihydro-1H-pyrazole derivatives (2a-s), based on the analgesia-inducing potential of 4,5-dihydro-1H-pyrazole moiety carrying compounds. Tail-clip and hot-plate tests, measuring centrally organized responses to a noxious stimulus, were performed in order to examine antinociceptive potential of the test compounds (100 mg/kg, i.p). In addition, peripherally mediated antinociceptive effect was evaluated by acetic acid-induced writhing tests. Motor coordination of the animals was tested in a Rota-rod apparatus. Among the tested compounds 2c, 2e, 2g, 2h, 2j, 2l, 2m, 2o and 2r prolonged the reaction time, measured in the tail-clip and hot-plate tests, with respect to the control values. The same compounds also decreased the quantity of acetic acid-induced writhing behaviours. In the Rota-rod tests, compound 2r was the only derivative decreasing the falling latency of mice. The obtained results indicated that some of the tested 4,5-dihydro-1H-pyrazole derivatives induce notable antinociceptive activity by effecting both of the central and peripheral nociceptive pathways. In addition, this study provided some information about structure-activity relationship for the compounds carrying similar chemical scaffold. Nevertheless, it should be noted that mechanism of action for these agents should be clarified with further detailed investigations.

WOS: 000540959600007, PubMed: 32388433, …, Hacettepe University Scientific Research Projects Coordination Unit, Ankara, TurkeyHacettepe University [THD-2018-16721], This study was supported by Hacettepe University Scientific Research Projects Coordination Unit, Ankara, Turkey (Project number: THD-2018-16721). We thank Hacettepe University Technology Transfer Center for providing English language editing service.

WOS: 000355933000011, In the present study, new 4-[4-[2-(2-(4-substituted benzylidene)hydrazinyl)-2-oxoethoxy]phenyl]-4-oxobutanoic acid derivatives were synthesized, and their anti-nociceptive and anti-inflammatory activities were investigated. In the synthesis of the compounds, 4-[4-(2-ethoxy-2-oxoethoxy)phenyl]-4-oxobutanoic acid molecule was used as starting material. The intermediate hydrazide compound (1) was reacted with appropriate aromatic aldehydes to obtain final hydrazone compounds (2a-i). All final compounds are well characterized by IR, H-1 NMR, C-13 NMR, and MS spectroscopic data. Hot-plate and tail-clip tests, measuring centrally organized responses to a nociceptive stimulus, were performed in order to examine anti-nociceptive potentials of the compounds (50 mg/kg). In addition, peripherally mediated anti-nociceptive effect was assessed by acetic acid-induced writhing tests. Further, carrageenan-induced paw edema method was used in order to evaluate the anti-inflammatory activity potential of the compounds. Motor coordination of the animals was examined in a Rota-rod apparatus. The obtained data indicated that compounds 2a, 2b, 2c, 2d, 2e, 2f decreased the number of acetic acid-induced writhing behaviors comparable with diclofenac sodium (10 mg/kg). The same compounds significantly decreased the paw swelling rate (%) of the mice with respect to the control values. These results indicated that compounds 2a, 2b, 2c, 2d, 2e, and 2f have peripherally mediated anti-nociceptive and anti-inflammatory activities. On the other hand, none of the tested compounds changed the reaction time of mice in hot-plate or tail-clip tests indicating that neither supraspinal nor spinal pathways were affected. The observed effect seems to be specific, since Rota-rod tests did not point out any motor impairment induced by the test compounds.

WOS: 000398360500015, 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 Acetyl cholinesterase (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., Anadolu University [1305S83], This study was financially supported by Anadolu University Scientific Research Projects Funds. Project No: 1305S83.

WOS: 000413397800016, PubMed ID: 28942286, Aims: This study was planned to examine the antidepressant potency of gallic acid (30 and 60 mg/kg), a phenolic acid widely distributed in nature, together with its possible underlying monoaminergic mechanisms. Main methods: Antidepressant-like activity was assessed using the tail suspension (TST) and the modified forced swimming tests (MFST). Locomotor activity was evaluated in an activity cage. Key findings: Administration of gallic acid at 60 mg/kg reduced the immobility duration of mice in both the TST and MFST without any changes in the locomotor activity. The anti-immobility effect observed in the TST was abolished with pre-treatment of p-chlorophenylalanine methyl ester (an inhibitor of serotonin synthesis; 100 mg/kg i. p. administered for 4-consecutive days), ketanserin (a 5-HT2A/2C antagonist; 1 mg/kg i. p.), ondansetron (a 5-HT3 antagonist; 0.3 mg/kg i. p.), alpha-methyl-para-tyrosine methyl ester (an inhibitor of catecholamine synthesis; 100 mg/kg i. p.), phentolamine (non-selective alpha-adrenoceptor antagonist; 5 mg/kg i. p.), SCH 23390 (a dopamine D1 antagonist; 0.05 mg/kg s. c.), and sulpiride (a dopamine D2/D3 antagonist; 50 mg/ kg i. p.). However, NAN 190 (a 5-HT1A antagonist; 0.5 mg/kg i. p.) and propranolol (a non-selective beta-adrenoceptor antagonist; 5 mg/kg i. p.) pre-treatments were ineffective at reversing the antidepressant-like effects of gallic acid. Significance: The results of the present study indicate that gallic acid seems to have a dual mechanism of action by increasing not only serotonin but also catecholamine levels in synaptic clefts of the central nervous system. Further alpha adrenergic, 5-HT2A/2C and 5-HT3 serotonergic, and D1, D2, and D3 dopaminergic receptors also seem to be involved in this antidepressant-like activity.

Bu calismanin amaci benzotiyazol halkasi tasiyan bazi bilesiklerin antinosiseptif ve anksiyolitik-benzeri etkilerinin incelenmesidir. 40 mg/kg dozda uygulanan test bilesiklerinin antinosiseptif etkileri kuyruk sikistirma, sicak plaka ve asetik asid ile induklenen kivranma testleri ile arastirilmistir. Bilesiklerin anksiyolitik-benzeri etkilerini incelemek icin delikli tahta ve yukseltilmis arti labirent testleri gerceklestirilmistir. Farelerin motor koordinasyonlarini degerlendirmek uzere Rota-rod cihazi kullanilmistir. Deneyler sonucunda 3f, 3g ve 3h kodlu bilesiklerin kuyruk sikistirma ve sicak plaka testlerinde hayvanlarin reaksiyon surelerini artirdigi ve 3e kodlu bilesigin ise asetik asid ile induklenen kivranma testinde farelerin kivranma sayilarini azalttigi belirlenmistir. Diger yandan, 3f, 3g ve 3h kodlu bilesikler delikli tahta testinde farelerin ilk bas daldirma surelerini kisaltirken toplam bas daldirma sayilarini artirmistir. Yukseltilmis arti labirent testinde ise ayni turevlerin farelerin ac i k kola giris say i lar i n i n ve ac i k kolda kalma surelerinin y u zdelerini art i rd igi ortaya konulmustur. Rota-rod testlerinde test bilesikleri farelerin donen milden dusme surelerini degistirmemistir. Tum bu bulgular, 3f, 3g ve 3h kodlu bilesiklerin santral antinosiseptif ve anksiyolitik-benzeri etki gosterdiklerine; 3e kodlu bilesigin ise periferal antinosiseptif etki gosterdigine isaret etmektedir.

WOS: 000321605200004, PubMed ID: 23639588, In the present study, we determined the potential anti-nociceptive activity of vitexin, a C-glycosylated flavone, by conducting some acute nociceptive tests in mice. Centrally mediated anti-nociceptive effect was evaluated by hot-plate and tail-clip tests, whereas peripherally mediated anti-nociception was assessed by acetic acid-induced writhing tests. Rota-rod test was performed to evaluate the probable effect of vitexin on the motor coordination of mice. Vitexin administered orally at doses of 10, 20, and 30 mg/kg significantly increased the reaction times of animals in the hot-plate and tail-clip tests and reduced the number of acetic acid-induced writhes and stretches in writhing tests, which clearly indicated the presence of the anti-nociceptive effect. This effect disappeared by pretreatment with naloxone (a non-selective opioid receptor antagonist, 5.48 mg/kg, i.p.), which indicated the involvement of opioid mechanisms in anti-nociception. We evaluated the contribution of mu, delta, and kappa subtypes of opioid receptors to the anti-nociceptive activity by using naloxonazine (7 mg/kg, s.c.), naltrindole (0.99 mg/kg, i.p.), and nor-binaltorphimine (1.03 mg/kg, i.p.), respectively. Pretreatment using these antagonists reversed the anti-nociceptive effect of vitexin in all the nociceptive tests, which indicated that mu, delta, and kappa opioid receptors contributed to the anti-nociceptive effect of this flavonoid. Falling latencies of mice in the Rota-rod test did not change upon the administration of vitexin, which indicated that vitexin showed specific anti-nociceptive effect. To the best of our knowledge, this is the first study on centrally and peripherally mediated anti-nociceptive effect of vitexin via opioid-related mechanisms

WOS: 000321387500003, PubMed ID: 23595553, In this study, we synthesized eight novel 1-phenyl-2-(4-substituted-piperazin-1-yl)-propanol derivatives and evaluated their antidepressant-like activities. The chemical structures of the synthesised compounds were elucidated by spectroscopy and elemental analyses. Potential antidepressant-like effects of the test compounds (20 mg kg(-1)) were investigated using the tail-suspension test and modified forced swimming test (MFST) in mice. Additionally, the spontaneous locomotor activity of the mice was assessed using the activity cage apparatus. Both the reference drug fluoxetine (20 mg kg(-1)) and the test compounds 3a-3e and 3g significantly shortened the immobility time of the mice in both the behavioural tests. These test compounds also increased the swimming time in MFST without any change in the climbing duration. Compounds 3c-3e and 3g were significantly more potent in inducing these effects than 3a and 3b. None of the compounds changed the locomotor activities of the animals, thus antidepressant-like effects of test compounds were specific. The findings support those of previous studies that reported antidepressant-like activities of aryl alkanol piperazine derivatives.

WOS: 000388251400004, PubMed ID: 27789142, In the current study, 14 new benzothiazole-piperazine compounds were designed to meet the structural requirements of acetylcholine esterase (AChE) inhibitors. The target compounds were synthesised in three steps. Structures of the newly synthesised compounds (7-20) were confirmed using IR, H-1 NMR, C-13 NMR, and HRMS methods. The inhibitory potential of the compounds on AChE (E.C.3.1.1.7, from electric eel) was then investigated. Among the compounds, 19 and 20 showed very good activity on AChE enzyme. Kinetics studies were performed to observe the effects of the most active compounds on the substrate-enzyme relationship. Cytotoxicity studies, genotoxicity studies, and theoretical calculation of pharmacokinetics properties were also carried out. The compounds 19 and 20 were found to be nontoxic in both of the toxicity assays. A good pharmacokinetics profile was predicted for the synthesised compounds. Molecular docking studies were performed for the most active compounds, 19 and 20, and interaction modes with enzyme active sites were determined. Docking studies indicated a strong interaction between the active sites of AChE enzyme and the analysed compounds, Anadolu University Scientific Projects Fund [1605S314], This study was financially supported by Anadolu University Scientific Projects Fund, Project No: 1605S314.

WOS: 000382334600043, PubMed ID: 27490523, 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., Anadolu University Scientific Research Projects Commission [1605S299], This study was supported by Anadolu University Scientific Research Projects Commission under grant No: 1605S299.

WOS: 000310420500006, PubMed ID: 23087135, Background: In this study, benzothiazolc-piperazine compounds were synthesized by condensing the functional groups of donepezil (DNP), FK-960, and sabeluzole, which are known to have therapeutic potential against Alzheimer's disease, with the aim of obtaining new and potent anti-Alzheimer agents. Methods: Initially, acetylcholinesterase/butyrylcholinesterase enzyme inhibition activities of the synthesized test compounds were investigated by Ellman's method. Effects of the compounds on a streptozotocin (STZ) model of Alzheimer's disease (SMAD) were investigated in rats. SMAD was established by intracerebroventricular (icy) injection of STZ (3 mg/kg), bilaterally. The elevated plus maze, Morris water maze, and active avoidance tests were used to examine the effects of test compounds (I, 5, and 10 mg/kg) on learning and memory parameters of icy STZ-injected rats. Effects of the test compounds on spontaneous locomotor activities of rats were examined with the activity cage test. Results: The compounds B2-B5 and DNP exhibited significant selective inhibitory potencies against acetylcholinesterase. Compounds B2 and B3 at 10 mg/kg doses and compounds B4 and B5 at 5 and 10 mg/kg doses, as well as the reference drug DNP (1 and 3 mg/kg), significantly improved the learning and memory parameters of animals in all cognition tests. None of the test compounds changed spontaneous locomotor activities. Conclusion: Results of the present study revealed that compounds B2-B5 repaired the parameters related to the learning and memory deficits of icy STZ-injected rats. Potencies of these test compounds were comparable to the activity of DNP., Anadolu University Research Foundation (Eskisehir, Turkey) [070321], This work was financially supported by Anadolu University Research Foundation (Eskisehir, Turkey). Project No. 070321. The authors would like to thank Dr. Erols ener from Anadolu University, Faculty of Pharmacy, Department of Analytical Chemistry, for his help in stereotaxic applications.

WOS: 000434717300008, PubMed ID: 29561803, 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), H-1 Nuclear Magnetic Resonance Spectroscopy (H-1-NMR), C-13 Nuclear Magnetic Resonance Spectroscopy (C-13-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., Anadolu University [1606S567], This study was financially supported by Anadolu University Scientific Research Projects. Commission, Project no. 1606S567.

WOS: 000350748200049, PubMed ID: 25658142, In an effort to develop potent antidepressant agents, new pyrazoline derivatives 2a-s were synthesized and evaluated for their antidepressant-like activity by tail suspension test (TST) and modified forced swimming test (MFST). The effects of the compounds on spontaneous locomotor activity were also investigated using an activity cage apparatus. Among these derivatives, compounds 2b, 2d, 2f, 2o, and 2r decreased both horizontal and vertical activity number of the mice. On the other hand, compounds 2a, 2h, 2j, 2k, 2l, 2m, and 2n, which did not induce any significant change in the locomotor activity, significantly shortened the immobility time of mice in TST and MFST, representing the presence of the antidepressant-like effect. Additionally, the same compounds increased the swimming time of mice in MFST without any change in climbing duration, similar to the reference drug fluoxetine (10 mg/kg). In the light of previous papers examining the effects of pyrazolines on central nervous system, this study, once more, pointed out remarkable antidepressant activity potential of pyrazoline derivatives., Anadolu University Scientific Research Projects Commission [1406S315, 1206S105], This study was supported by Anadolu University Scientific Research Projects Commission under the grant no: 1406S315 and 1206S105.

WOS: 000411499400085, PubMed ID: 28880242, 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., Anadolu University Scientific Projects Fund [1705S312], This study was financially supported by Anadolu University Scientific Projects Fund, Project No: 1705S312.

WOS: 000408602900137, PubMed ID: 28825626, 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, H-1-NMR, C-13-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., Anadolu University Scientific Research Projects Commission [1105S101, 1606S567], This study was financially supported by Anadolu University Scientific Research Projects Commission, Project no. 1105S101 and 1606S567.

WOS: 000307246100013, PubMed ID: 22797467, The aim of this study was to examine the effect of simvastatin (SMV), a 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitor, in rats fed with a standard or a high-fat diet (HFD) throughout the prenatal and the postnatal periods. The emotional status of the animals was evaluated by elevated plus-maze and modified forced swimming tests, whereas cognitive performance was assessed by a Morris water maze task. Morphological changes in the hippocampus were examined by design-based stereology. HFD exposure significantly increased blood serum triglycerides without altering cholesterol levels relative to the controls. After four weeks of oral SMV (5 mg/kg) administration, serum triglycerides reverted to the control level. SMV caused significant anxiolytic, antidepressant-like, and nootropic effects in animals fed the standard diet. In the HFD group, enhanced anxiety and depression, and reduced cognitive performances of animals were reversed by SMV treatment. Although a total volume estimation of the hippocampal subfields indicated no significant change among the groups, the total number of pyramidal neurons decreased significantly in animals fed the HFD; following SMV treatment, this detrimental effect was reversed. In conclusion, chronic SMV administration has significant therapeutic potential for the treatment of affective and cognitive disorders with or without altering the serum lipid profiles. Behavioural Pharmacology 23:582-592 (c) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

WOS: 000314659600034, PubMed ID: 23099258, The present study was designed to investigate the putative effect of vitexin, a flavone C-glucoside present in some drugs, medicinal plants and nutraceuticals, on the central nervous system. Vitexin (10-30 mg/kg) did not show significant alterations in the behaviour of mice tested in hole-board, plus-maze or activity cage tests. However, immobility time of the mice significantly reduced by vitexin administrations in both the tail-suspension and modified forced swimming tests. The anti-immobility effect of vitexin in the tail-suspension test was reversed with alpha-methyl-para-tyrosine methyl ester (AMPT, an inhibitor of catecholamine synthesis, 100 mg/kg, i.p.), yohimbine (an alpha(2)-adrenoceptor antagonist, 1 mg/kg, i.p.), NAN 190 (a 5-HT1A antagonist, 0.5 mg/kg, i.p.), SCH 23390 (a dopamine D-1 antagonist, 0.05 mg/kg, s.c.) and sulpiride (a dopamine D-2/D-3 antagonist, 50 mg/kg, i.p.). The same effect was not reversed, however, by p-chlorophenylalanine methyl ester (PCPA; an inhibitor of serotonin synthesis 100 mg/kg, i.p., administered for 4 consecutive days), ketanserin (a 5-HT2A/2C antagonist, 1-4 mg/kg, i.p.), ondansetron (a 5-HT3 antagonist, 0.1-0.4 mg/kg, i.p.), prazosin (an alpha(1)-adrenoceptor antagonist, 1-4 mg/kg, i.p.), or propranolol (a non-selective beta-adrenoceptor antagonist, 5-20 mg/kg, i.p.). These results suggest that the anti-depressant-like effect of vitexin is mediated through an increase in catecholamine levels in the synaptic cleft as well as through interactions with the serotonergic 5-HT1A, noradrenergic alpha(2), and dopaminergic D-1, D-2, and D-3 receptors. To our knowledge, this is the first study to show findings that indicate an anti-depressant-like effect of vitexin and its underlying mechanisms

WOS: 000303532800011, PubMed ID: 22553059, Novel thiadiazole derivatives bearing hydrazone moieties were synthesized through the reaction of 2-[(5-methyl-1,3,4-thiadiazol-2-yl)thio)]acetohydrazide with aldehydes/ketones. The chemical structures of the compounds were elucidated by H-1-NMR, C-13-NMR, MS-FAB spectral data, and elemental analyses. Behavioral effects of the test compounds in mice were examined by hole-board, activity cage, tail suspension and modified forced swimming tests (MFST). Antinociceptive activities were evaluated using the hot-plate and tail-clip methods. Results of the experiments indicated that the test compounds did not significantly change the exploratory behaviors or locomotor activities of animals in the hole-board and activity cage tests, respectively. Administration of the reference drug fluoxetine (10 mg/kg) and compounds 3a, 3b, 3c, 3j, 3k, and 3l significantly shortened the immobility times of animals in the tail suspension and MFST tests, indicating the antidepressant-like effects of these derivatives. Morphine (10 mg/kg) and compounds 3a, 3b, 3c, 3d, 3e, 3j, 3k, and 3l increased the reaction times of mice in both the hot-plate and tail-clip tests, indicating the antinociceptive effects of these compounds. To the best of our knowledge, this is the first study of central nervous system activities of chemical compounds carrying thiadiazole and hydrazone moieties together on their structures.

WOS: 000302928400017, PubMed ID: 22070986, In this study, the effect of Matricaria recutita L essential oil (MEO) on the central nervous system (CNS) of mice was investigated using some behavioral methods. Chemical profiling both by GC and GC-MS analyses of the hydrodistilled essential oil of M. recutita revealed alpha-bisabolol oxide A (28%), alpha-bisabolol oxide B (17.1%), (Z)-beta-Farnesene (15.9%) and alpha-bisabolol (6.8%) as the main components. Changes induced by MEO (25,50 and 100 mg/kg) and reference drug caffeine (25 mg/kg) in spontaneous locomotor activities and motor coordinations of mice were investigated by activity cage measurements and Rota-Rod tests, respectively. Open field, social interaction and elevated plus-maze tests were applied to assess the emotional state of the animals. Further, tail-suspension test was performed for evaluating the effect of MEO on depression levels of mice. As a result, at 50 and 100 mg/kg, MEO significantly increased the numbers of spontaneous locomotor activities, exhibited anxiogenic effect in the open field, elevated plus-maze and social interaction tests and decreased the immobility times of animals in tail suspension tests. The falling latencies in Rota-Rod tests did not change. This activity profile of MEO was similar to the typical psychostimulant caffeine. The exact mechanism of action underlying this stimulant-like effect should be clarified with further detailed studies

WOS: 000304463600012, This study was designed to evaluate the potential antinociceptive activities of some triazole-pyrazoline derivatives. All of the test compounds (100 mg/kg) increased the reaction times of mice in hotplate and tail-clip tests and decreased the total licking times of animals at both phases of formalin test. Compounds 3a, 3b, and 3c were more potent than the others in all nociception tests. None of the test compounds changed the spontaneous locomotor activities of animals. The findings obtained in this study supported the results of previous studies reporting the analgesic activities of triazole and/or pyrazoline derivatives.

WOS: 000301069500014, PubMed ID: 21657947, In the present study, some acetamide derivatives were synthesized and their potential analgesic activities were investigated. N-(benzothiazol-2-yl)-2-[(1-substituted-1H-tetrazol-5-yl) thio] acetamide derivatives were obtained by the nucleophilic substitution reaction of 2-chloro-N-(benzothiazole-2-yl) acetamides with appropriate tetrazol-5-thioles. The chemical structures of the compounds were elucidated by IR, H-1-NMR, C-13-NMR and FAB(+)-MS spectral data and elemental analyses. The prepared compounds were investigated for their potential analgesic properties against thermal, mechanical and chemical nociceptive stimuli using hot-plate, tail-clip and acetic acid-induced writhing tests, respectively. The assessment of motor coordination was carried out using Rota-Rod test. Tested compounds applied at 100 mg/kg doses caused significant decrease in acetic acid-induced writhing responses and increase in hot-plate and tail-clip latencies. None of the compounds exhibited destructive effect on motor coordination of the mice in Rota-Rod performance.

WOS: 000299691000013, PubMed ID: 21462070, This study was designed to investigate possible antidepressant-like effects of the extract prepared from the flowers of Hypericum montbretti Spach. (Guttiferae, Clusiaceae). Phytochemical constituents of the methanolic extract were analysed by HPLC method. The main flavonoid component was detected as rutin, and another highly concentrated phenolic compound was quercitrin. Antidepressant activity of the extract was examined by tail suspension and modified forced swimming tests, whereas the motor coordination of the animals was tested by the Rota-Rod apparatus. Reboxetine at a dose of 20 mg kg(-1) was used as a reference drug. Dose-dependent antidepressant activity was observed in both tests following the administration of extract at 100 and 250 mg kg(-1) doses. To the best of our knowledge, this is the first study reporting the antidepressant activity of H. montbretti extract. Additionally, the results of this work support previous papers reporting the antidepressant activity of rutin.

WOS: 000266030800031, PubMed ID: 18922604, In the present study, some pyrazoline derivatives were synthesized to investigate their potential antinociceptive activities. 1-[(Benzoxazole/benzimidazole-2-yl)thioacetyl]pyrazoline derivatives were obtained by reacting 3,5-diaryl-1-(2-chloroacetyl)pyrazolines with 2-marcaptobenzoxazole/benzimidazole. The chemical structures of the compounds were elucidated by IR, H-1 NMR and FAB(+)-MS spectral data and Elemental Analyses. All of the compounds (100 mg/kg) exhibited significant antinociceptive activities in both hot plate and acetic acid-induced writhing tests. Naloxone (5 mg/kg) pre-treatment reversed the antinociceptive activities suggesting the involvement of opioid system in the analgesic actions. None of the compounds impaired motor coordination of animals when assessed in the Rota-Rod model. These results support the previous papers reporting the opioid sensitive antinociceptive activities of various benzoxazole/benzimidazole-pyrazoline derivative compounds

WOS: 000270159800016, PubMed ID: 19784586, The aim of the present study was examining the effects of some 1,3,5-trisubstituted-2-pyrazoline derivatives on depression, anxiety and spontaneous locomotor activity parameters of mice. None of the compounds was effective at 50 mg/kg dose whereas at 100 and 200 mg/kg, pyrazoline-benzoxazole derivative test compound 4a and pyrazoline-benzimidazole derivative test compound 4d in the series were exhibited significant antidepressant effects in modified forced swimming tests. These two pyrazolines decreased the immobility and increased the swimming times of mice without any change in climbing durations suggesting the antidepressant-like effects of the test compounds. In spite of significant antidepressant effect, none of the compounds changed the exploratory parameters in hole-board tests or total numbers of spontaneous locomotor activities in activity cage measurements at any of the applied doses. In other words, neither anxiolytic nor sedative effects induced by the test compounds. The results obtained from this study supported the previous findings reporting the antidepressant activities of pyrazoline derivative compounds. Exact mechanism of the antidepressant action exhibited in the present study need to be clarified with further detailed investigations.