Yeni kinolin peptit konjugatlarının sitotoksik ve antimikrobiyal özelliklerinin araştırılması

Year 2024, , 53 - 59, 29.08.2024

Emine Adıyaman , Özgür Katrancıoğlu , Elif Apohan , Hasan Küçükbay

https://doi.org/10.58651/jomtu.1462635

Abstract

Amaç: Kanser, Türkiye’de ve dünyada ölüme neden olan önemli sağlık sorunlarından biridir. Günümüzde radyoterapi ve kemoterapi gibi birçok tedavi yöntemi kanser hastalarında uygulanmaktadır. Heterosiklik bileşikler arasında olan kinolin ve türevleri ilaçların geliştirilmesi açısından birçok biyolojik aktivite bulundurmaktadır. Kinolin bileşikleri, antikanser aktivite gösterdikleri için antikanser ilaç gelişiminde önemli bir rolü vardır.
Materyal ve Metot: Bu çalışmada, sentezlenmiş yedi farklı kinolin türevinin akciğer kanseri (A549) ve sağlıklı akciğer epitel (BEAS2B), karaciğer kanseri (Hep 3B) ve endotelial hücreler (HUVEC) üzerine sitotoksik etkileri belirlenmiştir. Farklı konsantrasyonlar uygulanmış ve farklı zaman aralıklarında IC50 değerleri hesaplanmıştır. Aynı zamanda bileşiklerin antimikrobiyal aktiviteleri de belirlenmiştir.
Bulgular: A549 hücre hattı üzerine bileşik 2’nin IC50 değerleri 10.48 μg/mL, 9.738 μg/mL, 10.14 μg/mL olarak tespit edilmiştir. Bileşik 6’nın aynı hücre hattı üzerine IC50 değerleri 7.307 μg/mL, 9.888 μg/mL, 10.63 μg/mL olarak belirlenmiştir.
Sonuç: Bileşik 2 ve 6’nın BEAS2B hücre hattı üzerine sitotoksik etkisi görülmüştür. Bileşiklerin antimikrobiyal etkileri çeşitli bakteri ve maya suşları üzerine minimum inhibisyon konsantrasyonu yöntemi ile belirlenmiştir. Bileşikler bakteriler ve maya üzerine antimikrobiyal etki göstermemiştir.

Keywords

Antimikrobiyal, Kinolin- Peptidkonjugatı, Sitotoksisite.

Supporting Institution

İnönü Üniversitesi

Project Number

2623

Thanks

Bu çalışmayı 2021/2623 proje numarasıyla destekleyen İnönü Üniversitesi Bilimsel Araştırma Projeleri Birimine teşekkür ederiz.

Investigation of the cytotoxic and antimicrobial properties of new quinoline peptide conjugates

Abstract

Background: Cancer is one of the most important health problems causing deaths in Turkey and the world. Nowadays, many treatment methods such as radiotherapy and chemotherapy are applied in cancer patients. Quinoline and its derivatives, which belong to heterocyclic compounds, have many biological activities for drug development. Quinoline compounds play a crucial role in the development of antitumor drugs due to their anticancer activity.
Materials and Methods: In this study, the cytotoxic effects of synthesized seven different quinoline derivatives on lung cancer (A549) and healthy lung epithelial cell (BEAS2B), liver cancer (Hep 3B), and endothelial cell (HUVEC) were determined. Different concentrations were applied and IC50 values were calculated at different time courses. The antimicrobial activites of the compounds were also determined.
Results: The IC50 values of compound 2 on the A549 cell line were determined to be 10.48 μg/mL, 9.738 μg/mL, and 10.14 μg/mL. IC50 values of compound 6 on the same cell line were determined to be 7.307 µg/mL, 9.888 µg/mL, 10.63 µg/mL.
Conclusions: Compounds 2 and 6 had a cytotoxic effect on the BEAS2B cell line. The antimicrobial activity of the compounds was determined by the minimum inhibition concentration method on different strains of bacteria and yeast. The compounds showed no antimicrobial activity on bacteria and yeast.

Keywords

Antimicrobial, Quinoline-peptide conjugates, Cytotoxic

Project Number

2623

Thanks

We would like to thank Inonu University Scientific Research Projects Unit for supporting this study as project number 2021/2623.

References

• Alegaon, S. G., Parchure, P., Araujo, L. D., Salve, P. S., Alagawadi, K. R., Jalalpure, S. S. & Kumbar, V. M. (2017). Quinoline-azetidinone hybrids: Synthesis and in vitro antiproliferation activity against Hep G2 and Hep 3B human cell lines. Bioorganic & Medicinal Chemistry Letters,27(7), 1566-1571.
• Alonso, C., Fuertes, M., Martín-Encinas, E., Selas, A., Rubiales, G., Tesauro, C. & Palacios, F. (2018). Novel topoisomerase I inhibitors. Syntheses and biological evaluation of phosphorus substituted quinoline derivates with antiproliferative activity. European Journal of Medicinal Chemistry, 149, 225-237.
• Altuner, D., Ekşi, S., Süleyman, H. & Turumtay, E. A. (2021). The effect of usnea longissima extract on lung cancer cell line (A549). ABC Research, 3(1), 1-5.
• Apohan, E., Yilmaz, U., Yilmaz, O., Serindag, A., Küçükbay, H., Yesilada, O. & Baran, Y. (2017). Synthesis, cytotoxic and antimicrobial activities of novel cobalt and zinc complexes of benzimidazole derivatives. Journal of Organometallic Chemistry,828, 52-58. Diaconu, D., Mangalagiu, V., Amariucai-Mantu, D., Antoci, V., Giuroiu, C. L. & Mangalagiu, I. I. (2020).
• Hybridquinoline-sulfonamidecomplexes(M2+) derivativeswithantimicrobialactivity, Molecules, 25(12), 2946. Dorababu, A. (2020). Report on recently (2017–20) designed quinoline‐based human cancer cell growth inhibitors. ChemistrySelect, 5(44), 13902-13915. Ferlin, M. G., Chiarelotto, G., Gasparotto, V., Dalla Via, L., Pezzi, V., Barzon, L., Palù, G. & Castagliuolo, I. (2005). Synthesis and in vitro and in vivo antitumor activity of 2-phenylpyrroloquinolin-4-ones. Journal of medicinal chemistry,48(9), 3417-3427.
• Gakhar, G., Ohira, T., Shi, A. B., Hua, D. H. & Nguyen, T. A. (2008). Antitumor effect of substituted quinolines in breast cancer cells. Drug Development Research,69(8), 526-534.
• Gasparotto, V., Castagliuolo, I., Chiarelotto, G., Pezzi, V., Montanaro, D., Brun, P., Palù, G., Viola, G. & Ferlin, M. G. (2006). Synthesis and biological activity of 7-phenyl-6, 9-dihydro-3 H-pyrrolo [3, 2-f] quinolin-9-ones: a new class of antimitotic agents devoid of aromatase activity. Journal of medicinal chemistry,49(6), 1910-1915.
• Giard, D. J., Aaronson, S. A., Todaro, G. J., Arnstein, P., Kersey, J. H., Dosik, H. & Parks, W. P. (1973). In vitro cultivation of human tumors: establishment of cell lines derived from a series of solid tumors. Journal of the National Cancer Institute, 51(5), 1417-1423.
• Güleç, G. & Büyükkınacı, A. (2011). Kanser ve psikiyatrik bozukluklar. Psikiyatride Güncel Yaklaşimlar, 3(2), 343-367. Haiba, M. E., Al-Abdullah, E. S., Ahmed, N. S., Ghabbour, H. A. & Awad, H. M. (2019). Efficient and easy synthesis of new Benzo [h] chromene and Benzo [h] quinoline derivatives as a new class of cytotoxic agents. Journal of Molecular Structure, 1195, 702-711.
• Jain, S., Chandra, V., Jain, P. K., Pathak, K., Pathak, D. & Vaidya, A. (2019). Comprehensive review on current developments of quinoline-based anticancer agents. Arabian Journal of Chemistry,12(8), 4920-4946.
• Jamshidi, H., Naimi‐Jamal, M. R., Safavi, M., RayatSanati, K., Azerang, P. & Tahghighi, A. (2022).
• Synthesisandbiologicalactivityprofile of noveltriazole/quinoline hybrids. Chemica lBiology & Drug Design. Jeyaraj, M., Rajesh, M., Arun, R., MubarakAli, D., Sathishkumar, G., Sivanandhan, G., Dev, G. K., Manickavasagam, M., Premkumar, K. & Thajuddin, N. (2013). An investigation on the cytotoxicity and caspase-mediated apoptotic effect of biologically synthesized silver nanoparticles using Podophyllum hexandrum on human cervical carcinoma cells. Colloids and Surfaces B: Biointerfaces,102, 708-717.
• Kumar, S., Shah, P., Tripathi, S. K., Khan, S. I. & Singh, I. P. (2022). Synthesisand in vitro evaluation of hydrazonomethyl-quinolin-8-ol and pyrazol-3-yl- quinolin-8-ol derivativesfor antimicrobial and antimalarial potential. MedicinalChemistry (Shariqah (United ArabEmirates)).
• Küçükbay, H., Gönül, Z., Küçükbay, F. Z., Tekin, Z., Angeli, A., Bartolucci, G. & Yeşilada, Ö. (2021). Synthesis of new 7‐amino‐3, 4‐dihydroquinolin‐2 (1H)‐one‐peptide derivatives and their carbonic anhydrase enzyme inhibition, antioxidant, and cytotoxic activities. Archiv der Pharmazie, 354(11), 2100122.
• Lewandowska, A. M., Lewandowski, T., Rudzki, M., Rudzki, S. & Laskowska, B. (2021). Cancer prevention - review paper. Annals of Agricultural and Environmental Medicine, 28(1), 11-19.
• Ökçesiz, A. & Ündeğer Bucurgat, Ü. (2017). Stem cells in cytotoxicity studies. Ankara Ecz. Fak. Derg., 41(2): 1-14.
• Siegel, R. L., Miller, K. D., Fuchs, H. E. & Jemal, A. (2021). Cancer statistics, 2021. CA: A Cancer Journal For Clinicians, 71(1), 7-33.
• Thakare, P. P., Shinde, A. D., Chavan, A. P., Nyayanit, N. V., Bobade, V. D. &Mhaske, P. C.(2020). Synthesisand biological evaluation of new 1, 2, 3‐triazolyl‐pyrazolyl‐quinoline derivatives as potential antimicrobial agents. Chemistry Select, 5(15), 4722-4727.
• Thumar, N. J., &Patel, M. P. (2011). Synthesis and antimicrobial activity of some new n‐substituted quinoline derivatives of 1h‐pyrazole. Archivder Pharmazie, 344(2), 91-101.
• Wang, C.-H., Shih, W.-C., Chang, H. C., Kuo, Y.-Y., Hung, W.-C., Ong, T.-G. & Li, W.-S. (2011). Preparation and characterization of amino-linked heterocyclic carbene palladium, gold, and silver complexes and their use as anticancer agents that act by triggering apoptotic cell death. Journal of Medicinal Chemistry,54(14), 5245-5249.
• Yernale, G. (2021). A comprehensive review on the biological interest of quinoline and its derivatives. Bioorganic & Medicinal Chemistry,32, 115973.