HeLa ve Beas-2B Hücre Hatlarına Karşı Benzimidazolyum Tuzlarının İn Vitro Sitotoksik Aktivite Çalışmaları

Yıl 2020, , 505 - 513, 15.04.2020

Senem Akkoc

https://doi.org/10.17714/gumusfenbil.613631

Öz

1H-benzo[d]imidazol çekirdeği içeren altı farklı heterosiklik bileşik (S1-S6) iki basamakta hazırlandı ve
yapıları farklı spektroskopik yöntemler kullanılarak karakterize edildi. Sentezlenen
heterosiklik bileşikler insan serviks adenokarsinom (HeLa) ve insan sağlıklı
akciğer (Beas-2B) hücre hatlarına karşı test edildi. Pozitif kontrol ilaç
olarak cisplatin aynı şartlar altında serviks hücre hattına karşı denendi.
Bileşik S4'ün HeLa hücre hattına karşı yüksek sitotoksik aktivite gösterdiği (IC₅₀:
3.72 ± 0.14 µM) bulundu.
Çalışmanın son basamağında, ilaç adayları ile etkileştirilen hücrelerin renkli
görüntüleri konfokal mikroskobu kullanılarak alındı. 

Anahtar Kelimeler

Benzimidazol, Heterosiklik Bileşik, Konfokal, Sitotoksik Aktivite

In Vitro Cytotoxic Activity Studies of Benzimidazolium Salts against HeLa and Beas-2B Cell Lines

Öz

Six different heterocyclic
compounds containing 1H-benzo[d]imidazole nuclei (S1-S6) were prepared in two steps and their structures were characterized
using different spectroscopic methods. The synthesized heterocyclic compounds
were tested against human cervix adenocarcinoma (HeLa) and human healthy lung
(Beas-2B) cell lines. Cisplatin as a positive control drug was tested against the cervix
cell line under the same conditions. Compound S4 was found to exhibit high cytotoxic activity against HeLa cell
line (IC₅₀: 3.72 ± 0.14 µM). In the last step of the study, color
images of the cells interacted with the drug candidates were taken using confocal
microscope.

Anahtar Kelimeler

Benzimidazole, Heterocyclic Compound, Confocal, Cytotoxic Activity

Kaynakça

• Abdelgawad, M.A., Bakr, R.B., Ahmad, W., Al-Sanea, M.M. ve Elshemy, H.A.H., 2019. New Pyrimidine-Benzoxazole/Benzimidazole Hybrids: Synthesis, Antioxidant, Cytotoxic Activity, In Vitro Cyclooxygenase and Phospholipase A2-V Inhibition. Bioorganic Chemistry, 92, 103218.
• Akkoç, S., 2019a. Derivatives of 1-(2-(Piperidin-1-yl)ethyl)-1H-benzo[d]imidazole: Synthesis, Characterization, Determining of Electronic Properties and Cytotoxicity Studies. ChemistrySelect, 4, 4938-4943.
• Akkoç, S., 2019b. Antiproliferative Activities of 2-Hydroxyethyl Substituted Benzimidazolium Salts and Their Palladium Complexes Against Human Cancerous Cell Lines. Synthetic Communications, 49, 2903-2914.
• Akkoç, S., Kayser, V. ve İlhan, İ.Ö., 2019. Synthesis and In Vitro Anticancer Evaluation of Some Benzimidazolium Salts. Journal of Heterocyclic Chemistry, 56, 2934-2944.
• Akkoç, S., Kayser, V., İlhan, İ.Ö., Hibbs, D.E., Gök, Y., Williams, P.A., Hawkins, B. ve Lai, F., 2017. New Compounds Based on a Benzimidazole Nucleus: Synthesis, Characterization and Cytotoxic Activity Against Breast and Colon Cancer Cell Lines. Journal of Organometallic Chemistry, 839, 98-107.
• Akkoç, S., Özer İlhan, İ., Gök, Y., Upadhyay, P.J. ve Kayser, V., 2016. In Vitro Cytotoxic Activities of New Silver and PEPPSI Palladium N-heterocyclic Carbene Complexes Derived from Benzimidazolium Salts. Inorganica Chimica Acta, 449, 75-81.
• Aslan, H.G., Akkoç, S. ve Kökbudak, Z., 2020. Anticancer Activities of Various New Metal Complexes Prepared from a Schiff Base on A549 Cell Line. Inorganic Chemistry Communications, 111, 107645.
• Bansal, Y. ve Silakari, O., 2012. The Therapeutic Journey of Benzimidazoles: A Review. Bioorganic Medicinal Chemistry, 20, 6208-6236.
• Busschots, S., O’Toole, S., O’Leary, J.J. ve Stordal, B., 2015. Carboplatin and Taxol Resistance Develops More Rapidly in Functional BRCA1 Compared to Dysfunctional BRCA1 Ovarian Cancer Cells. Experimental Cell Research, 336, 1-14.
• Cheng, J., Xie, J. ve Luo, X., 2005. Synthesis and Antiviral Activity Against Coxsackie Virus B3 of Some Novel Benzimidazole Derivatives. Bioorganic and Medicinal Chemistry Letters, 15, 267-269.
• Farahat, A.A., Ismail, M.A., Kumar, A., Wenzler, T., Brun, R., Paul, A., Wilson, W.D. ve Boykin, D.W., 2018. Indole and Benzimidazole Bichalcophenes: Synthesis, DNA Binding and Antiparasitic Activity. European Journal of Medicinal Chemistry, 143, 1590-1596.
• Gök, Y., Akkoç, S., Çelikal, Ö.Ö., Özdemir, İ. ve Günal, S., 2019. In Vitro Antimicrobial Studies of Naphthalen-1-ylmethyl Substituted Silver N-heterocyclic Carbene Complexes. Arabian Journal of Chemistry, 12, 2513-2518.
• Gök, Y., Akkoç, S., Çelikal, Ö.Ö., Özdemir, İ., Günal, S. ve Sayin, E., 2013. N-Functionalized Benzimidazol-2-ylidene Silver Complexes: Synthesis, Characterization and Antimicrobial Studies. Turkish Journal of Chemistry, 37 (6) 1007-1013.
• Özil, M., Parlak, C. ve Baltaş, N., 2018. A Simple and Efficient Synthesis of Benzimidazoles Containing Piperazine or Morpholine Skeleton at C-6 Position as Glucosidase Inhibitors with Antioxidant Activity. Bioorganic Chemistry, 76, 468-477.
• Rojas-Aguirre, Y., Castillo, I., Hernández, D.J., Nogueda-Torres, B., Márquez-Navarro, A., Villalobos, J.C., Sánchez-Bartéz, F., Sánchez-Torres, L., Gracia-Mora, I., Castillo, R. ve Hernández-Luis, F., 2012. Diversity in the Supramolecular Interactions of 5,6-Dichloro-2-(trifluoromethyl)-1H-benzimidazole with Modified Cyclodextrins: Implications for Physicochemical Properties and Antiparasitic Activity. Carbohydrate Polymers, 87, 471-479.
• Rosenberg, B., Vancamp, L., Trosko, J.E. ve Mansour, V.H. 1969. Platinum Compounds: a New Class of Potent Antitumour Agents. Nature, 222, 385-386.
• Sharma, R., Bali, A. ve Chaudhari, B.B., 2017. Synthesis of Methanesulphonamido-Benzimidazole Derivatives as Gastro-sparing Antiinflammatory Agents with Antioxidant Effect. Bioorganic and Medicinal Chemistry Letters, 27, 3007-3013.
• Shingalapur, R.V., Hosamani, K.M., Keri, R.S. ve Hugar, M.H., 2010. Derivatives of Benzimidazole Pharmacophore: Synthesis, Anticonvulsant, Antidiabetic and DNA Cleavage Studies. European Journal of Medicinal Chemistry, 45, 1753-1759.
• Taha, M., Mosaddik, A., Rahim, F., Ali, S., Ibrahim, M. ve Almandil, N.B., 2018. Synthesis, Antiglycation and Antioxidant Potentials of Benzimidazole Derivatives. Journal of King Saud University - Science, 32, 191-194.
• To, K.K.W., Poon, D.C., Wei, Y., Wang, F., Lin, G. ve Fu, L.W., 2016. Data Showing the Circumvention of Oxaliplatin Resistance by Vatalanib in Colon Cancer. Data in Brief, 7, 437-444.
• Tonelli, M., Novelli, F., Tasso, B., Vazzana, I., Sparatore, A., Boido, V., Sparatore, F., La Colla, P., Sanna, G., Giliberti, G., Busonera, B., Farci, P., Ibba, C. ve Loddo, R., 2014. Antiviral Activity of Benzimidazole Derivatives. III. Novel Anti-CVB-5, Anti-RSV and Anti-Sb-1 Agents. Bioorganic Medicinal Chemistry, 22, 4893-4909.
• Yang, Y., Guo, L., Ge, X., Shi, S., Gong, Y., Xu, Z., Zheng, X. ve Liu, Z., 2019. Structure-Activity Relationships for Highy Potent Half-Sandwich Organoiridium (III) Anticancer Complexes with CˆN-Chelated Ligands. Journal of Inorganic Biochemistry, 191, 1-7.
• Wheate, N.J., Walker, S., Craig, G.E. ve Oun, R., 2010. The Status of Platinum Anticancer Drugs in the Clinic and in Clinical Trials. Dalton Transactions, 39, 8113-8127.
• World Health Organization, 2018. Cancer, http://www.who.int/news-room/fact-sheets/detail/cancer. 07 Kasım 2019.