Synthesis, In Vitro Anticholinesterase and Antimicrobial Evaluation of New 1,3,4-Thiadiazole-Piperazine Derivatives

Yıl 2019, Cilt: 6 Sayı: 2, 424 - 432, 26.12.2019

Ulviye Acar Çevik , Begüm Nurpelin Sağlık

https://doi.org/10.35193/bseufbd.601344

Cited By: 1

Öz

In this study, 8 new compounds having 2-((5-substituted-1,3,4-thiadazol-2-yl)amino)-2-oxoethyl-4- substituepiperazine-1-carbodithioate structures were synthesized, antimicrobial and anticholinesterase activities were evaluated. The structures of synthesized compounds were proved by 1H NMR, 13C NMR and mass spectra. The synthesized compounds were tested for antibacterial activity against eight bacteria strains and antifungal activity against four fungus strains. When the antibacterial activities of the compounds were examined, it was found that the compounds 3c, 3d, 3g and 3h were effective against E. faecalis (ATCC 29212) and E. faecalis (ATCC 51922) with MIC value of 25 µg/mL. It was determined that the carbon chain at the para position of piperazine increased the activity but where as the addition of benzyl group to the para position (3a, 3b, 3e, 3f) did not affect the activity. Furthermore, the acetylcholinesterase activity of the synthesized compounds was examined but none of the compounds showed AChE inhibitory activity as much as standard drug Donepezil.

Anahtar Kelimeler

1, 3, 4-Thiadiazole, Antimicrobial, Anticholinesterase, Piperazine

Yeni 1,3,4-Tiyadiazol-Piperazin Türevlerinin Sentezi, İn Vitro Antikolinesteraz ve Antimikrobiyal Değerlendirilmesi

Öz

Bu çalışmada
2-((5-substitüe-1,3,4-tiyadiazl-2-il)amino)-2-oksoetil-4- substituepiperazin-1-karboditiyat
yapısında 8 yeni bileşiğin sentezi yapılarak, antimikrobiyal ve
antikolinesteraz aktiviteleri incelenmiştir. Sentezlenen bileşiklerin yapıları ¹H-NMR,
¹³ C-NMR ve kütle spektrumları kullanılarak kanıtlanmıştır. Aktivite
sonuçları incelendiğinde, çoğu bileşiğin S. aureus (ATCC 25923), E.
fecalis (ATCC 29212), E. fecalis (ATCC 51922), L. monocytogenes
(ATCC 1911), K. pneumoniae (ATCC 700603), P. aeruginosa (ATCC
27853), E.coli (ATCC 35218), E. coli (ATCC 25923), C. albicans
(ATCC 90028), C. glabrata (ATCC 90030), C. krusei (ATCC  6258), C. parapsilopsis (ATCC 22019)
karşı standart bileşikler olan kloramfenikol ve ketakonazol kadar etkili
olmadıkları görülmüştür. Bileşiklerin antibakteriyel aktiviteleri
incelendiğinde 3c, 3d, 3g ve 3h kodlu bileşiklerin diğer bileşiklere göre daha
yüksek aktiviteye sahip olduğu görülmüştür. Piperazinin para konumunda bulunan
karbon zincirinin aktiviteyi arttırdığı (3c, 3d, 3g, 3h), ancak para konumuna benzil grubunun eklenmesinin (3a, 3b, 3e, 3f) aktiviteyi etkilemediği
belirlenmiştir. Ayrıca, sentezlenen bileşiklerin asetilkolinesteraz aktivitesi
incelenmiş ancak bileşiklerden hiçbiri standart ilaç Donepezil kadar AChE
inhibe edici aktivite göstermemiştir.

Anahtar Kelimeler

Thiadiazole, Antimicrobial, Anticholinesterase, Piperazine

Kaynakça

• [1] Er, M., Özer, A., Direkel, Ş., Karakurt, T., Tahtaci, H. (2019). Novel substituted benzothiazole and Imidazo [2,1-b][1,3,4] Thiadiazole derivatives: Synthesis, characterization, molecular docking study, and investigation of their in vitro antileishmanial and antibacterial activities. Journal of Molecular Structure, 1194, 284-296.
• [2] Mannam, M.R., & Kumar, P. (2019). Synthesis of Novel 1‐(5‐(Benzylsulfinyl)‐3‐methyl‐1,3,4‐thiadiazol‐2 (3H)‐ylidene)‐thiourea/urea derivatives and evaluation of their antimicrobial activities. Journal of Heterocyclic Chemistry, 56, 2179-2191.
• [3] Barmak, A., Niknam, K., Mohebbi, G., & Pournabi, H. (2019). Antibacterial studies of hydroxyspiro [indoline-3, 9-xanthene] trione against spiro [indoline3, 9-xanthene] trione and their use as acetyl and butyrylcholinesterase inhibitors. Microbial pathogenesis, 130, 95-99.
• [4] Kamboj, V. K., Kapoor, A., & Jain, S. (2019). Synthesis, Antimicrobial, and Antioxidant Screening of Aryl Acetic Acid Incorporated 1,2,4-Triazolo-1,3,4-Thiadiazole Derivatives. Journal of Heterocyclic Chemistry, 56, 1376-1382.
• [5] Mali, S.N., Sawant, S., Chaudhari, H.K., & Mandewale, M.C. (2019). In silico appraisal, synthesis, antibacterial screening and DNA cleavage for 1, 2, 5-thiadiazole derivative. Current computer-aided drug design, 15, 445-455.
• [6] Ali, A.A.A., Lee, Y.R., Chen, T.C., Chen, C.L., Lee, C.C., Shiau, C.Y., ... & Huang, H.S. (2016). Novel anthra [1, 2-c][1, 2, 5] thiadiazole-6, 11-diones as promising anticancer lead compounds: Biological evaluation, characterization & molecular targets determination. PloS one, 11, e0154278.
• [7] Kaplancıklı, Z.A., Turan-Zitouni, G., Revial, G., Işcan, G. (2004). Synthesis of some dithiocarbamate derivatives and their antimicrobial activity. Phosphorus, Sulfur, and Silicon, 179, 1449-1454.
• [8] Ellman, G. L., Courtney, K. D., Andres Jr, V., & Featherstone, R. M. (1961). A new and rapid colorimetric determination of acetylcholinesterase activity. Biochemical pharmacology, 7, 88-95.
• [9] Wikler, M.A. (2006). Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically: approved standard. CLSI (NCCLS), 26, M7-A7.
• [10] Pandit, N., Shah, K., Agrawal, N., Upmanyu, N., Shrivastava, S. K., & Mishra, P. (2016). Synthesis, characterization and biological evaluation of some novel fluoroquinolones. Medicinal Chemistry Research, 25(5), 843-851.
• [11] Levent, S., Acar Çevik, U., Sağlık, B. N., Özkay, Y., Can, Ö. D., Özkay, Ü. D., & Uçucu, Ü. (2017). Anticholinesterase activity screening of some novel dithiocarbamate derivatives including piperidine and piperazine moieties. Phosphorus, Sulfur, and Silicon and the Related Elements, 192(4), 469-474.