Benzotiyazol Halkası Taşıyan Bazı Bileşiklerin Antinosiseptif ve Anksiyolitik-Benzeri Etkileri

Yıl 2019, , 122 - 129, 30.06.2019

Ümide Demir Özkay , Umut İrfan Üçel Nazlı Turan Yücel , Özgür Devrim Can

https://doi.org/10.30607/kvj.524391

Öz

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.

Anahtar Kelimeler

Benzotiyazol halkası, antinosiseptif, anksiyolitik, Rota-rod

Antinociceptive and Anxiolytic-Like Effects of Some Compounds Carrying Benzothiazole Ring

Öz

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.

Anahtar Kelimeler

Benzothiazole ring, antinociceptive, anxiolytic, Rota-rod

Kaynakça

• Ali R, Siddiqui N. New benzo[d]thiazol-2-yl-aminoacetamides as potential anticonvulsants: synthesis, activity and prediction of molecular properties. Arch Pharm (Weinheim). 2015; 348(4):254-265.
• Amnerkar ND, Bhusari KP. Synthesis, anticonvulsant activity and 3D-QSAR study of some prop-2-eneamido and 1-acetyl-pyrazolin derivatives of aminobenzothiazole. Eur J Med Chem. 2010; 45(1):149-159.
• Anzini M, Chelini A, Mancini A, Cappelli A, Frosini M, Ricci L, Valoti M, Magistretti J, Castelli L, Giordani A, Makovec F, Vomero S. Synthesis and biological evaluation of amidine, guanidine, and thiourea derivatives of 2-amino(6-trifluoromethoxy)benzothiazole as neuroprotective agents potentially useful in brain diseases. J Med Chem. 2010; 53(2):734-744.
• Aouad MR, Soliman MA, Alharbi MO, Bardaweel SK, Sahu PK, Ali AA, Messali M, Rezki N, Al-Soud YA. Design, Synthesis and anticancer screening of novel benzothiazole-piperazine-1,2,3-triazole hybrids. Molecules. 2018; 23(11):pii: E2788.
• Azam MA, Dharanya L, Mehta CC, Sachdeva S. Synthesis and biological evaluation of some novel pyrazolopyrimidines incorporating a benzothiazole ring system. Acta Pharm. 2013; 63(1):19-30.
• Can OD, Altintop MD, Ozkay UD, Uçel UI, Doğruer B, Kaplancikli ZA. Synthesis of thiadiazole derivatives bearing hydrazone moieties and evaluation of their pharmacological effects on anxiety, depression, and nociception parameters in mice. Arch Pharm Res. 2012a; 35(4):659-669.
• Can OD, Demir Özkay U, Kıyan HT, Demirci B. Psychopharmacological profile of Chamomile (Matricaria recutita L.) essential oil in mice. Phytomedicine. 2012b; 19(3-4):306-310.
• Can ÖD, Demir Özkay Ü, Üçel Uİ. Anti-depressant-like effect of vitexin in BALB/c mice and evidence for the involvement of monoaminergic mechanisms. Eur J Pharmacol. 2013; 699(1-3):250-257.
• Can ÖD, Turan N, Alyu F. 1,3,5-triaril-4,5-dihidro-1h-pirazol türevi bazı bileşiklerin benzodiazepin reseptörleri aracılıklı anksiyolitik-benzeri etkileri. Cukurova Med J. 2016; 41(2):304-315.
• Carboni S, Hiver A, Szyndralewiez C, Gaillard P, Gotteland JP, Vitte PA. AS601245 (1,3-benzothiazol-2-yl (2-[[2-(3-pyridinyl) ethyl] amino]-4 pyrimidinyl) acetonitrile): a c-Jun NH2-terminal protein kinase inhibitor with neuroprotective properties. J Pharmacol Exp Ther. 2004; 310(1):25-32.
• Coelho LP, Reis PA, de Castro FL, Gayer CR, da Silva Lopes C, da Costa e Silva MC, de Carvalho Sabino KC, Todeschini AR, Coelho MG. Antinociceptive properties of ethanolic extract and fractions of Pterodon pubescens Benth. seeds. J Ethnopharmacol. 2005; 98(1-2):109-116.
• Costanzo MJ, Yabut SC, Almond HR Jr, Andrade-Gordon P, Corcoran TW, De Garavilla L, Kauffman JA, Abraham WM, Recacha R, Chattopadhyay D. Potent, small-molecule inhibitors of human mast cell tryptase. Antiasthmatic action of a dipeptide-based transition-state analogue containing a benzothiazole ketone. J Med Chem. 2003; 46(18):3865-3876.
• D’Amour FE, Smith DL. A method for determining loss of pain sensation. J Pharmacol Exp Ther. 1941; 72(1):74-79.
• Demir Özkay U, Can OD. Anti-nociceptive effect of vitexin mediated by the opioid system in mice. Pharmacol Biochem Behav. 2013; 109:23-30.
• Demir Özkay Ü, Can ÖD, Sağlık BN, Turan N. A benzothiazole/piperazine derivative with acetylcholinesterase inhibitory activity: Improvement in streptozotocin-induced cognitive deficits in rats. Pharmacol Rep. 2017a; 69(6):1349-1356.
• Demir Özkay Ü, Kaya C, Acar Çevik U, Can ÖD. Synthesis and antidepressant activity profile of some novel benzothiazole derivatives. Molecules. 2017b; 22(9):pii: E1490.
• File SE, Pellow S. The effects of triazolobenzodiazepines in two animal tests of anxiety and in the holeboard. Br J Pharmacol. 1985; 86(3):729-735.
• Gabra BH, Sirois P. Beneficial effect of chronic treatment with the selective bradykinin B1 receptor antagonists, R-715 and R-954, in attenuating streptozotocin-diabetic thermal hyperalgesia in mice. Peptides. 2003; 24(8):1131-1139.
• Gökce M, Cakir B, Erol K, Sahin MF. Synthesis and antinociceptive activity of [(2-oxobenzothiazolin-3-yl)methyl]-4-alkyl/aryl-1,2,4-triazoline-5-thiones. Arch Pharm (Weinheim). 2001; 334(8-9):279-283.
• Hamdy NA, Abdel-Aziz HA, Kamel GM, Fakhr IM. Convenient synthesis, anti-inflammatory, analgesic and ulcerogenic activites of some new bis-hydrazones and pyrazole derivatives. Acta Pol Pharm. 2013; 70(3):469-480.
• Hassan MZ, Khan SA, Amir M. Design, synthesis and evaluation of N-(substituted benzothiazol-2-yl)amides as anticonvulsant and neuroprotective. Eur J Med Chem. 2012; 58:206-213.
• Hroch L, Aitken L, Benek O, Dolezal M, Kuca K, Gunn-Moore F, Musilek K. Benzothiazoles - scaffold of interest for CNS targeted drugs. Curr Med Chem. 2015; 22(6):730-747.
• Kaplancikli ZA, Turan-Zitouni G, Ozdemir A, Can Ov, Chevallet P. Synthesis and antinociceptive activities of some pyrazoline derivatives. Eur J Med Chem. 2009; 44(6):2606-2610.
• Karali N, Güzel O, Ozsoy N, Ozbey S, Salman A. Synthesis of new spiroindolinones incorporating a benzothiazole moiety as antioxidant agents. Eur J Med Chem. 2010; 45(3):1068-1077.
• Kasap M, Can, ÖD. Opioid system mediated anti-nociceptive effect of agomelatine in mice. Life Sci. 2016; 163:55-63.
• Keri RS, Quintanova C, Marques SM, Esteves AR, Cardoso SM, Santos MA. Design, synthesis and neuroprotective evaluation of novel tacrine-benzothiazole hybrids as multi-targeted compounds against Alzheimer's disease. Bioorg Med Chem. 2013; 21(15):4559-4569.
• Koster R, Anderson M, De Beer EJ. Acetic acid for analgesic screening. Fed Proc. 1959; 18:412-415.
• Kumar KV, Krishna DR, Palit G. Histaminergic H1 receptors mediate L-histidine-induced anxiety in elevated plus-maze test in mice. Behav Pharmacol. 2007; 18(3):213-217.
• Liu DC, Zhang HJ, Jin CM, Quan ZS. Synthesis and biological evaluation of novel benzothiazole derivatives as potential anticonvulsant agents. Molecules. 2016; 21(3):164.
• Mariappan G, Prabhat P, Sutharson L, Banerjee J, Patangia U, Nath S. Synthesis and antidiabetic evaluation of benzothiazole derivatives. J Korean Chem Soc. 2012; 56(2):251-256.
• Moreno-Díaz H, Villalobos-Molina R, Ortiz-Andrade R, Díaz-Coutiño D, Medina-Franco JL, Webster SP, Binnie M, Estrada-Soto S, Ibarra-Barajas M, León-Rivera I, Navarrete-Vázquez G. Antidiabetic activity of N-(6-substituted-1,3-benzothiazol-2-yl)benzenesulfonamides. Bioorg Med Chem Lett. 2008; 18(9):2871-2877.
• Muttu CT, Bhanushali MD, Hipparagi SM, Tikare VP, Karigar A. Microwave assisted synthesis and evaluation of some fluoro chloro 2-N-(substituted Schiff’s bases)aminobenzothiazoles derivatives for their antiinflamatory activity. Int J Res Ayurveda Pharm. 2010; 1(2):522-528.
• Osmaniye D, Levent S, Karaduman AB, Ilgın S, Özkay Y, Kaplancıklı ZA. Synthesis of new benzothiazole acylhydrazones as anticancer agents. Molecules. 2018; 23(5):pii: E1054.
• Park SH, Sim YB, Kang YJ, Kim SS, Kim CH, Kim SJ, Seo JY, Lim SM, Suh HW. Hop extract produces antinociception by acting on opioid system in mice. Korean J Physiol Pharmacol. 2012; 16(3):187-192.
• Pinheiro MM, Boylan F, Fernandes PD. Antinociceptive effect of the Orbignya speciosa Mart. (Babassu) leaves: evidence for the involvement of apigenin. Life Sci. 2012; 91(9-10):293-300.
• Sampath C, Holbik M, Krenn L, Butterweck V. Anxiolytic effects of fractions obtained from Passiflora incarnata L. in the elevated plus maze in mice. Phytother Res. 2011; 25(6):789-795.
• Sarkar S, Siddiqui AA, Saha SJ, De R, Mazumder S, Banerjee C, Iqbal MS, Nag S, Adhikari S, Bandyopadhyay U. Antimalarial activity of small-molecule benzothiazole hydrazones. Antimicrob Agents Chemother. 2016; 60(7):4217-4228.
• Sasaki-Hamada S, Sacai H, Sugiyama A, Iijima T, Saitoh A, Inagaki M, Yamada M, Oka J. Riluzole does not affect hippocampal synaptic plasticity and spatial memory, which are impaired by diazepam in rats. J Pharmacol Sci. 2013; 122(3):232-236.
• Siddiqui N, Rana A, Khan SA, Ahsan W, Alam MS, Ahmed S. Analgesic and antidepressant activities of benzothiazole-benzamides. Biomed Pharmacol J. 2008; 1(2):297-300.
• Siddiqui N, Rana A, Khan SA, Bhat MA, Haque SE. Synthesis of benzothiazole semicarbazones as novel anticonvulsants–the role of hydrophobic domain. Bioorg Med Chem Lett. 2007; 17(15):4178-4182.
• Singh MK, Tilak R, Nath G, Awasthi SK, Agarwal A. Design, synthesis and antimicrobial activity of novel benzothiazole analogs. Eur J Med Chem. 2013; 63:635-644.
• Takeda H, Tsuji M, Matsumiya T. Changes in head-dipping behavior in the hole-board test reflect the anxiogenic and/or anxiolytic state in mice. Eur J Pharmacol. 1998; 350(1):21-29.
• Thakkar SS, Thakor P, Ray A, Doshi H, Thakkar VR. Benzothiazole analogues: Synthesis, characterization, MO calculations with PM6 and DFT, in silico studies and in vitro antimalarial as DHFR inhibitors and antimicrobial activities. Bioorg Med Chem. 2017; 25(20):5396-5406.
• Ugwu DI, Okoro UC, Ukoha PO, Gupta A, Okafor SN. Novel anti-inflammatory and analgesic agents: synthesis, molecular docking and in vivo studies. J Enzyme Inhib Med Chem. 2018; 33(1): 405-415.
• Wang S, Chen Y, Zhao S, Xu X, Liu X, Liu BF, Zhang G. Synthesis and biological evaluation of a series of benzoxazole/benzothiazole-containing 2,3-dihydrobenzo[b][1,4]dioxine derivatives as potential antidepressants. Bioorg Med Chem Lett. 2014; 24(7):1766-1770.
• Wong CH, Dey P, Yarmush J, Wu WH, Zbuzek VK. Nifedipine-induced analgesia after epidural injection in rats. Anesth Analg. 1994; 79(2):303-306.Woolfe G, MacDonald AD. The evaluation of the analgesic action of pethidine hydrochloride (Demerol). J Pharmacol Exp Ther. 1944; 80(3):300-307.
• Zha GF, Leng J, Darshini N, Shubhavathi T, Vivek HK, Asiri AM, Marwani HM, Rakesh KP, Mallesha N, Qin HL. Synthesis, SAR and molecular docking studies of benzo[d]thiazole-hydrazones as potential antibacterial and antifungal agents. Bioorg Med Chem Lett. 2017; 27(14):3148-3155.