Tiyosemikarbazit ve bis-1,2,4-triazol Türevlerinin Antikanser, Apoptotik ve Antibakteriyal Etkileri

Year 2020, , 1124 - 1133, 26.09.2020

Gülden Koçak , Emine Akdemir

https://doi.org/10.17798/bitlisfen.679216

Abstract

Bu çalışmada, çıkış maddesi [piridin-2,5-dikarbohidrazin (2)] ile tiyosemikarbazit türevleri [2,2’-(piridin-2,5-diildikarbonil-bis(N-etilhidrazinkarbotiyoamit) (3B) ve 2,2’-(piridin-2,5-diildikarbonil)-bis(N-(p-metoksifenil)hidrazinkarbotiyoamit (3C)] ve bu bileşiklerin halkalaşmasında oluşan bis-1,2,4-triazol türevlerinin [5,5-piridin-2,5-diilbis(4-etil-4H-1,2,4-triazol-3-tiyol) (4B) ve 5,5’-piridin-2,5diilbis[4-(4-metoksifenil)-4H-1,2,4-triazol-3-tiyol)] (4C)] in vitro ortamda prostat kanser hücre hattı (PC-3) üzerindeki antikanser ve apoptotik etkileri ile bazı gram pozitif ve gram negatif bakteriler üzerindeki antibakteriyel etkileri belirlenmiştir. Antikanser etki sonuçlarına göre tüm maddelerin artan konsantrasyonlara bağlı olarak canlı kanser hücre sayısında azalma tespit edilmiştir. Tüm uygulanan maddelerde en yüksek sitotoksik etkinin 500 μM konsantrasyonda olduğu belirlenmiştir. Tüm maddelerin apoptozu tetiklediği belirlenmiş olup apoptotik indeks oranlarına bakıldığında en düşük apoptotik indeks oranı 4B maddesi uygulandığında, en yüksek apoptotik indeks oranı ise 3C maddesi uygulandığında tespit edilmiştir. Antibakteriyel çalışmada tüm bileşiklerin gram pozitif bakteriler üzerinde gram negatiflere nazaran daha fazla etkili olduğu görülmüştür.

Keywords

PC-3, Tiyosemikarbazit, Triazol, Antikanser, Apoptotik etki

Supporting Institution

Bingöl Üniversitesi BÜBAP

Project Number

BAP-712-297-2015

Anticancer, Apoptotic and Antibacterial, Effects of Thiosemicarbazid and bis-1,2,4-Triazole Derivatives

Abstract

In this study in vitro anticancer and apoptotic activities on the prostate cell line (PC-3) and antibacterial effects on some gram positive and gram negative bacteria of pyridine-2,5-dicarbohydrazine and synthesized thiosemicarbazide derivatives [2,2′ -(pyridine-2,5-diyldicarbonyl)-bis(N-ethylhydrazinecarbothioamide) (3B)and [2,2′-(pyridine-2,5-diyldicarbonyl)-bis[N-(p-methoxyphenyl)hydrazinecarbothioamide] (3C)] and bis-1,2,4- triazole-3-thiol derivatives [5,5′-pyridine-2,5-diylbis(4-ethyl-4H-1,2,4-triazole3-thiol) (4B) and 5,5′-pyridine-2,5- diylbis(4-(4-methoxy-phenyl)-4H1,2,4-triazole-3-thiol) (4C)] were determined. According to the results of cytotoxic studies cell numbers decreased by the concentration increase of all compounds. The maximum cytotoxic effects were found on 500 μM concentration. As a result of apoptotic activity it is found out that all of the compounds triggered the apoptosis and the lowest index was on 4B and the highest index was on 3C compounds. Antibacterial tests showed that all compounds used in this study were more effective on gram positive bacteria then gram negative bacteria. 

Keywords

PC-3, thiosemicarbazid, triazole, anticancer, apoptotic effects, antibacterial effects

Project Number

BAP-712-297-2015

References

• 1. Bray F., Ferlay J., Soerjomataram I., Siegel R.L., Torre L.A., Jemal A. 2018. Global Cancer Statistics 2018 GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries, CA: Cancer Journal of Clinicians, 68: 394–424.
• 2. Bostwick D.G., Burke H.B., Djakiew D., Euling S., Ho S.M., Landolph J., Morrison H., Sonawane B., Shifflett T., Waters D.J., Timms B. 2004. Human prostate cancer risk factors, Cancer, 101(10): 2371-490.
• 3. Jemal A., Murray T., Ward E., Samuels A., Tiwari R.C., Ghafoor A., Thun M.J. 2005. Cancer statistics, 2005, CA: Cancer Journal for Clinicians, 55: 10-30.
• 4. Banerjee S., Ganguly S., Sen K.K. 2013. A Review on 1, 2, 4 -Triazoles, Journal of Advanced Pharmacy Education & Research, 3(3): 102-115.
• 5. Bulut N., Kocyigit U.M., Gecibesler I.H., Dastan T., Karci H., Taslimi P., Dastan S.D., Gulcin I., Cetin A. 2018. Synthesis of some novel pyridine compounds containing bis-1,2,4-triazole/thiosemicarbazidemoiety and investigation of their antioxidant properties, carbonic anhydrase, and acetylcholinesterase enzymes inhibition profiles, Journal of Biochemical Molecular Toxicology, DOI: 10.1002/jbt.22006, 1-10.
• 6. Mothes-Wagner U., Reitze H.K., Seitz K.A. 1990. Environmental actions of agrochemicals 1. Side-effects of the herbicide 3-amino-1,2,4-triazole on a laboratory acarine/host-plant interaction (Tetranychus urticae/Phaseolus vulgaris) as revealed by electron microscopy, Experimantal and Applied Acarology, 8(2): 27-40.
• 7. Taj T., Kamble R.R., Gireesh T., Badami B.V. 2011. An Expeditious Green Synthesis of Schiff Bases and Azetidinones Derivatised with 1,2,4-Triazoles, Journal of Chemical Sciences, 123(5): 657–666.
• 8. Hassan F.A., Younus K.W. 2012. Biological Evaluation of Some Azole Derivatives in Cooling Fluids (Lubricant Oils), Research Journal of Biological Sciences, 7(1): 48-51. 9. Abdullah H.M., Jassim I.K., Safi M.N. 2012. Synthesis and Characterization of New Heterocyclic Compounds with Studying Its Biological Activity, Kerbala Journal of Pharmaceutical Sciences, 4: 119-135.
• 10. Jabar A., Al-Mufrgeiy S.S. 2012. Synyhesis and Antibacterial Activities of New 3-Amino-2-Methyl- Quinazolin-4(3H)-One Derivatives, American Journal of Chemistry, 2 (3): 150-156.
• 11. Pardeshi S.P., Patil S.V., Patil R., Bobade V.D. 2014. Synthesis and Antimicrobial Activities of Some 1,2,4- Triazolo[3,4-b][1,3,4]thiadiazoles and 1,2,4-Triazolo [3,4-b][1,3,4]thiadiazines Bearing Bistrifluoromethyl phenyl Moiety, Journal of Chemical Pharmaceutical Research, 6 (4): 675-681.
• 12. Bekircan O., Menteşe E., Ülker S., Kucuk C. 2014. Synthesis of Some New 1,2,4-Triazole Derivatives Starting from 3-(4-Chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol with Anti-Lipase and Anti-Urease Activities, Arch. Pharm. Chem. Life Sci, 347: 387–397.
• 13. Sripriya1 S., Subha C., Selvaraj A. 2013. The Inhibition Chemistry of 2-Amino, 5-Phenyl 1, 3, 4-Triazole for Aluminium in Hydrochloric Acid Solution, IOSR- JAC, 6 (2): 25-29.
• 14. Sengupta A.K., Garg M. 1988. Studies on Potential Pestisides-Part XIV Synthesis and Biological Activities of Some New Thiosemicarbazide and Triazole Derivatives, Definition of Science, 31(2): 91-96.
• 15. Er J.C., Tang M.K., Chia C.G., Liew H., Vendrell M., Chang Y.T. 2014. Megastockes BODIPY-triazoles as Environmentally Sensitive Turn-on Fluorescent Dyes, Journal of Chemical Sciences, 4: 2168-2176.
• 16. Bulut V.N., Duran C., Gundogdu A., Soylak M., Yildirim N., Tufekci M. 2010. A Triazole Derivatives as A New Acid-Base Indicator, Bulletin of the Chemical Society Ethiopia, 24(3): 457-460.
• 17. Cassani S., Kovarich S., Roy P.P., Van der Wal L., Gramatica P. 2013. Daphnia and Fish Toxicity of (Benzo) triazoles: Validated QSAR Models, and Interspecies Quantitative Activity-Activity Modeling, Journal of Hazardous Materials, 258-259: 50-60.
• 18. Kisgen J. 2015. Lippincott Illustrated Reviews: Pharmacology 6th edition, Wolters Kluwer, Hong Kong.
• 19. Karcı H. 2013. Yeni bis-1,2,4-triazol türevlerinin antioksidan aktivitelerinin incelenmesi. Bingöl Üniversitesi, Fen Bilimleri Enstitüsü, Yüksek Lisans Tezi, 58s, Bingöl.
• 20. Benedict R.G., Brady L.R. 1972. Antimicrobial activity of mushroom metabolites, Journal of Pharmaceutical Sciences, 61(11): 1820-1822.
• 21. Biemer J.J. 1973. Antimicrobial Susceptibility Testing by the Kirby-Bauer Disc Diffusion Method, Annals of Clinical Laboratory Science, 3(2): 135-140.
• 22. Subrahmanya B.K., Boja P., Jagadeesh P.D., Prashantha N., Shivarama H.B. 2009. Synthesis and antitumor activity studies of some new fused 1,2,4-triazole derivatives carrying 2,4-dichloro-5-fluorophenyl moiety, European Journal of Medicinal Chemistry, 44: 5066–5070.
• 23. Al-Soud Y.A., Al-Dweri M.N., Al-Masoudi N.A. 2004. Synthesis, antitumor and antiviral properties of some 1,2,4-triazole derivatives, Farmaco, 59(10): 775-783.
• 24. Demirbas N., Ugurluoglu R., Demirbas A. 2002. Synthesis of 3-Alkyl(Aryl)-4-alkylidenamino-4,5-dihydro- 1H-1,2,4-triazol-5-ones and 3-Alkyl-4-alkylamino-4,5-dihydro-1H-1,2,4-triazol-5-ones as Antitumor Agents, Bioorganic and Medicinal Chemistry, 10: 3717–3723.
• 25. Sztanke K., Tuzimski T., Rzymowska J., Pasternak K., Kandefer-Szerszen M. 2008. Synthesis, determination of the lipophilicity, anticancer and antimicrobial properties of some fused 1,2,4-triazole derivatives, European Journal of Medicinal Chemistry, 43: 404-409.
• 26. Porter A.G., Jänicke R.U. 1999. Emerging roles of caspase-3 in apoptosis, Cell Death and Differentiation, 6: 99-145.
• 27. Klimešová V., Zahajská L., Waisser K., Kaustová J., Möllman U. 2004. Synthesis and antimycobacterial activity of 1,2,4-triazole 3-benzylsulfanyl derivatives, Farmaco, 59(4): 279–288.
• 28. Jain R.K., Mishra V.K., Kashaw V. 2017. Synthesis and Antimicrobial Activity of Some New 1,2,4-Trizoles, Asian Journal of Chemistry; 29(6):1317-1322.