Evaluation of Antifungal and Antiproliferative Effects of Two Different Organic Compounds with Cyclobutane Ring

Year 2023, , 351 - 357, 07.11.2023

Mustafa Çiçek Tuğçe Deniz Karaca İbrahim Yılmaz

https://doi.org/10.15671/hjbc.1311376

Abstract

In the modern world, where there is a growing demand for new substances with anticancer and antifungal activities, Schiff bases and phthalimide derivatives, which exhibit a wide diversity of biological activity, have become the focus of new therapeutic research studies. Accordingly, this study examined the anti-proliferative effects of two distinct compounds synthesized by cyclobutane substitution on breast cancer and liver cancer cell lines, which are two major cancer types, were investigated with MTT method and their antifugal activities on C. albicans were evaluated with disk diffusion method. Minimum inhibitory concentrations of the compounds against C. albicans were also determined in the scope of the study. The results revealed that the synthesized Schiff base was more effective on the breast cancer cell line MCF7, whereas the phthalimide-derivative was more effective against the liver cancer cell line Mahlavu. Besides, according to the data related to the antifungal properties of the compounds, it can be inferred that both compounds are suitable for further investigation as potential building blocks for the creation of novel and efficient antifungal medications.

Keywords

Antifungal, Anti-proliferative, Schiff base, Phthalimide derivative.

Siklobütan Halkalı İki Farklı Organik Bileşiğin Antifungal ve Antiproliferatif Etkilerinin Değerlendirilmesi

Abstract

Antikanser ve antifungal etkinliklere sahip yeni bileşiklere duyulan gereksinimin giderek arttığı günümüzde, çeşitli biyolojik aktiviteler sergileyebilen bazı organik bileşiklerden Schiff bazlarının ve ftalimid türevlerinin yeni terapötik araştırma-geliştirme çalışmalarında önemli olduğu görülmektedir. Bu nedenle bu çalışmada, siklobütan sübstitüsyonu ile sentezlenen iki farklı bileşiğin, yaygın kanser türleri arasında olan meme kanseri ve karaciğer kanseri hücre hatları üzerindeki anti-proliferatif etkileri MTT yöntemi ile, C. albicans üzerindeki antifugal aktiviteleri ise disk difüzyon yöntemi ile incelenmiştir. Ek olarak bileşiklerin C. albicans’a karşı minimum inhibitör konsantrasyonları da çalışma kapsamında tespit edilmiştir. Sonuçlar, sentezlenen Schiff bazının meme kanseri hücre hattı MCF7 üzerinde daha etkili olduğunu, buna karşılık ftalimid-türevinin ise karaciğer kanseri hücre hattı Mahlavu'ya karşı daha etkili olduğunu ortaya koymuştur. Ayrıca, bileşiklerin antifungal özelliklerine ilişkin verilere dayanılarak; söz konusu bileşiklerin her ikisinin de yeni ve etkili antifungal ilaçların elde edilmesi için gerçekleştirilecek yeni çalışmalara potansiyel yapı taşları olarak katkı sağlayacağı düşünülmektedir.

Keywords

Antifungal, Anti-proliferatif, Schiff bazı, Ftalimid türevi

References

• E.Ö. Karaca, Yeni Schiff Bazı Bileşiklerinin Sentezi ve Yapılarının Aydınlatılması, J. Polytech., 21 (2018) 245–249.
• V.M. Barot, S.A. Gandhi, U.H. Patel, M.C. Patel, Synthesis, X-Ray Powder Diffraction Studies and Antimicrobial Activities of Novel Chalcone Derivatives, Chem. Sci. Trans., 4 (2015) 642–648.
• A. Rani, M. Kumar, R. Khare, H.S. Tuli, Schiff bases as an antimicrobial agent: A review Anti-Neoplastic effects of Garcinol View project Schiff bases as an antimicrobial agent: A review, J. Biol. Chem. Sci., 2 (2015) 62–91.
• M.M. Abd-Elzaher, A.A. Labib, H.A. Mousa, S.A. Moustafa, M.M. Ali, A.A. El-Rashedy, Synthesis, anticancer activity and molecular docking study of Schiff base complexes containing thiazole moiety, Beni-Suef Univ. J. Basic Appl. Sci., 5 (2016) 85–96.
• K.N. Jean-Baptiste, K.C. Guillaume, O.Z. Adama, K.A.L. Claude, D.K. Jacques, K.B. Antoine, Z. Nahosse, Synthesis, Characterization and Biological Evaluation of New Series of Schiff Bases Derived from Hexamethylenediamine as Potential Antibacterial and Antifungal Agents, IRA-International J. Appl. Sci. (ISSN 2455-4499), 7 (2017) 69–74.
• N. Al-Lami, Z. Amer, R.A. Ali, Pryparation, characterization and biological activity of new derivatives of 2-biphenyl-3-aminomethylimidazo(1,2-a)pyrimidine, J. Pharm. Sci. Res., 10 (2018) 3344–3350.
• A.P. King, H.A. Gellineau, S.N. Macmillan, J.J. Wilson, Physical properties, ligand substitution reactions, and biological activity of Co(iii)-Schiff base complexes, Dalt. Trans., 48 (2019) 5987–6002.
• I. Bernadette Amali, M.P. Kesavan, V. Vijayakumar, N. Indra Gandhi, J. Rajesh, G. Rajagopal, Structural analysis, antimicrobial and cytotoxic studies on new metal(II) complexes containing N 2 O 2 donor Schiff base ligand, J. Mol. Struct., 1183 (2019) 342–350.
• B.A. Ansell, Juvenile chronic arthritis, in Drug Treat. Rheum. Dis., 2nd ed., ADIS Health Science Press, (1982): p. 186.
• B. Shivarama Holla, B. Veerendra, M.K. Shivananda, B. Poojary, Synthesis characterization and anticancer activity studies on some Mannich bases derived from 1,2,4-triazoles, Eur. J. Med. Chem., 38 (2003) 759–767.
• K. Van Derpoorten, J. Balzarini, E. De Clercq, J.H. Poupaert, Anti-HIV activity of N-1-adamantyl-4-aminophthalimide, Biomed. Pharmacother., 51 (1997) 464–468.
• H. Miyachi, A. Ogasawara, A. Azuma, Y. Hashimoto, Tumor necrosis factor-alpha production-inhibiting activity of phthalimide analogues on human leukemia THP-1 cells and a structure-activity relationship study, Bioorganic Med. Chem., 5 (1997) 2095–2102.
• R. Antunes, H. Batista, R.M. Srivastava, G. Thomas, C.C. Araujo, New phthalimide derivatives with potent analgesic activity: II, Bioorganic Med. Chem. Lett., 8 (1998) 3071–3076.
• H. Miyachi, A. Azuma, T. Kitamoto, K. Hayashi, S. Kato, M. Koga, B. Sato, Y. Hashimoto, Potent novel nonsteroidal androgen antagonists with a phthalimide skeleton, Bioorganic Med. Chem. Lett., 7 (1997) 1483–1488.
• E.P. Sampaio, G. Kaplan, A. Miranda, J.A.C. Nery, C.P. Miguel, S.M. Viana, E.N. Sarno, The Influence of Thalidomide on the Clinical and Immunologic Manifestation of Erythema Nodosum Leprosum, J. Infect. Dis., 168 (1993) 408–414.
• T. Eisen, C. Boshoff, I. Mak, F. Sapunar, M.M. Vaughan, L. Pyle, S.R.D. Johnston, R. Ahern, I.E. Smith, M.E. Gore, Continuous low dose Thalidomide: A phase II study in advanced melanoma, renal cell, ovarian and breast cancer, Br. J. Cancer, 82 (2000) 812–817.
• A. Çukurovali, I. Yilmaz, H. Özmen, M. Ahmedzade, A new mesitylenic cyclobutane substituted schiff base ligand and its Co(II), Cu(II), Ni(II), and Zn(II) complexes, Heteroat. Chem., 12 (2001) 42–46.
• N. Özdemir, M. Dinçer, I. Yilmaz, A. Çukurovali, 1-Methyl-1-phenyl-3-(phthalimidoacetyl)-cyclobutane, Acta Crystallogr. Sect. E Struct. Reports Online, 60 (2004) 14–16.
• A. Çukurovali, I. Yilmaz, M. Ahmedzade, Synthesis and characterization of a new cyclobutane-substituted Schiff base ligand and its Co(II), Cu(II) and Ni(II) complexes, Synth. React. Inorg. Met. Chem., 30 (2000) 843–853.
• M.A. Akhmedov, I.K. Sardarov, I.M. Akhmedov, R.R. Kostikov, A. V. Kisin, N.M. Babaev, ChemInform Abstract: Formation of Substituted Cyclobutanes in the Reaction of 2-(2-Methyl-2- propenyl)-3-chloromethyloxirane with Aromatic Hydrocarbons, ChemInform, 23 (2010) no-no.
• J. Guinea, S. Recio, P. Escribano, M. Torres-Narbona, T. Peláez, C. Sánchez-Carrillo, M. Rodríguez-Créixems, E. Bouza, Rapid Antifungal Susceptibility Determination for Yeast Isolates by Use of Etest Performed Directly on Blood Samples from Patients with Fungemia, J. Clin. Microbiol., 48 (2010) 2205.
• B.E. Tefon Öztürk, B. Eroğlu, E. Delik, M. Çiçek, E. Çiçek, Comprehensive Evaluation of Three Important Herbs for Kombucha Fermentation, Food Technol. Biotechnol., 61 (2023).
• World Health Organization, WHO fungal priority pathogens list to guide research, development and public health action, Licence CC BY-NC-SA 3.0 IGO, 1 (2022) 1–48.
• F. Bongomin, S. Gago, R.O. Oladele, D.W. Denning, Global and multi-national prevalence of fungal diseases—estimate precision, J. Fungi, 3 (2017).
• J. Ceramella, D. Iacopetta, A. Catalano, F. Cirillo, R. Lappano, M.S. Sinicropi, A Review on the Antimicrobial Activity of Schiff Bases: Data Collection and Recent Studies, Antibiotics, 11 (2022).
• L.A. Torre, R.L. Siegel, E.M. Ward, A. Jemal, Global cancer incidence and mortality rates and trends - An update, Cancer Epidemiol. Biomarkers Prev., 25 (2016) 16–27.
• H. Sung, J. Ferlay, R.L. Siegel, M. Laversanne, I. Soerjomataram, A. Jemal, F. Bray, Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries, CA. Cancer J. Clin., 71 (2021) 209–249.
• A. Hameed, M. al-Rashida, M. Uroos, S. Abid Ali, K.M. Khan, Schiff bases in medicinal chemistry: a patent review (2010-2015), Expert Opin. Ther. Pat., 27 (2017) 63–79.
• K.S. Munawar, S.M. Haroon, S.A. Hussain, H. Raza, Schiff Bases: Multipurpose Pharmacophores with Extensive Biological Applications, J. Basic Appl. Sci., 14 (2018) 217–229.
• L.J. Li, C. Wang, Y. Qiao, X.Y. Yang, X.X. Hua, J.L. Du, Platinum(II) complexes of reduced amino acid ester Schiff bases: Synthesis, characterization, and antitumor activity, Res. Chem. Intermed., 40 (2014) 413–424.
• T.F.F. Magalhães, C.M. da Silva, L.B.F. dos Santos, D.A. Santos, L.M. Silva, B.B. Fuchs, E. Mylonakis, C.V.B. Martins, M.A. de Resende-Stoianoff, de Fátima, Cinnamyl Schiff bases: synthesis, cytotoxic effects and antifungal activity of clinical interest, Lett. Appl. Microbiol., 71 (2020) 490–497.
• L. Pan, X. Li, C. Gong, H. Jin, B. Qin, Synthesis of N-substituted phthalimides and their antifungal activity against Alternaria solani and Botrytis cinerea, Microb. Pathog., 95 (2016) 186–192.
• H. Jelali, L. Mansour, E. Deniau, M. Sauthier, N. Hamdi, An Efficient Synthesis of Phthalimides and Their Biological Activities, Polycycl. Aromat. Compd., 42 (2022) 1806–1813.