Synthesis and Characterization of Novel Calix[4]arene Schiff Base Derivatives and Cytotoxicity Effect Evaluation on Cancer Cell Lines

Ayşen Işık; Kezban Uçar Çifçi; Hayrani Eren Bostancı; Yusuf Tutar; Ahmet Koçak; Mustafa Yılmaz

doi:10.17776/csj.1173347

EN

Synthesis and Characterization of Novel Calix[4]arene Schiff Base Derivatives and Cytotoxicity Effect Evaluation on Cancer Cell Lines

Abstract

In this study, four stages were used to create brand-new p-tert-butyl-calix [4] arene Schiff base derivatives. First, p-tert-butyl-phenol and formaldehyde are reacted to create p-tert-butyl-calix [4] arene (1). In the following step, methyl bromoacetate and p-ter-butyl-calix [4] arene (1) were combined with acetone and reflux to create the p-tert-butyl-calix [4] arene diester complex (2). The third step involves reacting the diester compound (2) and hydrazine hydrate to create the p-tert-butyl-calix [4] arene hydrazinamide molecule (3). In the final stage, calix [4] arene Schiff base derivatives (4a-d) were produced in good yields by combining compound (3), p-tert-butyl-calix [4] arene hydrazinamide, and various aldehyde derivatives with reflux in EtOH. Through the use of 1H-NMR, 13C-NMR, infrared spectroscopy, and elemental analysis, the structures of produced compounds were verified. Four distinct cancer lines are linked to the antitumor activity of synthetic chemicals. (HT-29, a human colon cancer cell line, PC-3, a human prostate cancer cell line, C6, a rat glioma cell line and MCF-7, a human breast cancer cell line). Weak antitumor activity was seen in synthetic substances. However, only compound 4b was found to have potential efficacy against C6 and HT-29. It is clear that compound 4b, which has a nitro substitute on the phenyl ring, draws attention due to its increased activity.

Keywords

Supporting Institution

Selcuk University Scientific Research Projects Coordinatorship (BAP)

Project Number

20111003

References

[1] Baig S., Seevasant I., Mohamad J., Mukheem A., Huri H.Z., Kamarul T., Potential of apoptotic pathway-targeted cancer therapeutic research: Where do we stand?, Cell Death Dis., 7(1) (2016) 2058.
[2] Narang A. S., & Desai D. S., Anticancer drug development, In Pharmaceutical perspectives of cancer therapeutics, New York, NY: Springer, (2009) 49-92.
[3] Guo S., Song Y., He Y., Hu X. Y., and Wang L., Highly efficient artificial light-harvesting systems constructed in aqueous solution based on supramolecular self-assembly, Angew Chem. Int. Ed., 57 (2018) 3163–3167.
[4] Yokoyama T., and Mizuguchi M., Crown ethers as transthyretin amyloidogenesis inhibitors, J. Med. Chem., 62 (2019) 2076–2082.
[5] Zhang Y. M., Xu Q. Y., and Liu Y., Molecular recognition, and biological application of modified β-cyclodextrins, Sci. Chin., 62 (2019) 1–12.
[6] Böhmer V., Calixarenes, macrocycles with (almost) unlimited possibilities, Angew. Chem. Int. Ed. Engl., 34 (2010) 713–745.
[7] Bauer D., Andrae B., Gaß P., Trenz D., Becker S., and Kubik S., Functionalisable acyclic cucurbiturils, Org. Chem. Front., 6 (2019) 1555–1560.
[8] Geraci C., Consoli G. M., Galante E., Bousquet E., Pappalardo M., and Spadaro A., Calix[4]arene decorated with four Tn antigenglycomimetic units and P3CS immunoadjuvant: synthesis, characterization, and anticancer immunological evaluation, Bioconjugate Chem., 19 (2008) 751–758.

[9] Da Silva E., Lazar A. N., & Coleman A. W., Biopharmaceutical applications of calixarenes, Journal of Drug Delivery Science and Technology, 14(1) (2004) 3-20.
[10] Yousaf A., Abd Hamid S., Bunnori N. M., & Ishola A. A., Applications of calixarenes in cancer chemotherapy: facts and perspectives, Drug design, development and therapy, 9 (2015) 2831.
[11] Al-Hakimi A.N., Alminderej F., Aroua L., Alhag S.K., Alfaifi M.Y., Mahyoub, J.A., Eldin I., Elbehairi S., Alnafisah A.S., Design, synthesis, characterization of zirconium (IV), cadmium (II) and iron (III) complexes derived from Schiff base 2-aminomethylbenzimidazole, 2-hydroxynaphtadehyde and evaluation of their biological activity, Arab. J. Chem., 13 (2020) 7378–7389.
[12] Maurya R.C., Chourasia J., Rajak D., Malik B.A., Mir J.M., Jain N., Batalia S., Oxovanadium(IV) complexes of bioinorganic and medicinal relevance: synthesis, characterization and 3D molecular modeling of some oxovanadium(IV) complexes involving O, N-donor environment of salicylaldehyde-based sulfa drug Schiff bases, Arab. J. Chem., 9 (2016) 1084-1100.
[13] El-Saied F.A., Salem T.A., Shakdofa M.M.E., Al-Hakimi A.N., Radwan A.S., Antitumor activity of synthesized and characterized Cu (II), Ni (II) and Co (II) complexes of hydrazone-oxime ligands derived from 3-(hydroxyimino) butan-2-one, Beni-Suef Univ. J. basic Appl. Sci., 7 (2018) 420-429.
[14] El-Saied F.A., Salem T.A., Shakdofa M.M.E., Al-Hakimi A.N., Anti-neurotoxic evaluation of synthetic and characterized metal complexes of thiosemicarbazone derivatives, Appl. Organomet. Chem., 32 (2018) 4215.
[15] Gutsche C. D., and Iqbal M., p-ter-Butylcalix[4]arene, Org. Synth., 68 (1990a) 234-237.
[16] Arnaud-Neu F., Collins E. M., Deasy M., Ferguson G., Harris S. J., Kaitner B., ... & Marques E., Synthesis, X-ray crystal structures, and cation-binding properties of alkyl calixaryl esters and ketones, a new family of macrocyclic molecular receptors, Journal of the American Chemical Society, 111(23) (1989) 8681-8691.
[17] Narang A. S., & Desai D. S., Anticancer drug development, In Pharmaceutical perspectives of cancer therapeutics, New York, NY: Springer, (2009) 49-92.
[18] Fang C., Tang S., Wang X., Sun X., Li H., Xu Y., Gu X., Xu J., Lasiokaurin derivatives: synthesis, antimicrobial and antitumor biological evaluation, and apoptosis-inducing effects, Arch Pharm. Res. (Seoul), 40 (2017) 796e806.
[19] Mosmann T., Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays, J. Immunol. Methods, 65 (1983) 55e63.
[20] Karahan A., Yardan A., Yahsi Y., Kara H., Kurtaran R., N2O2 Tipi Schiff Bazı Ligandı ile Sentezlenen Cu(II) Kompleksinin X-Işını Yapısı ve Termal Özelliği, SDU Journal of Science (E-Journal), 8(2) (2013) 163-174.
[21] Erdik E., , Organik Kimyada Spektroskopik Yöntemler, Fersa Matbaacılık San. Tic. Ltd. Şti., Ankara, (1993).
[22] Balcı M., Nükleer Manyetik Rezonans Spektroskopisi, Gökçe Ofset Matbaacılık Ambalaj, Tur. Org. San. Ve Tic. Ltd. Şti., Ankara, (2000) 25-206.

Details

Primary Language

English

Subjects

-

Journal Section

Research Article

Authors

Ayşen Işık ^*
0000-0002-1280-0019
Türkiye

Kezban Uçar Çifçi
0000-0002-4758-4141
Türkiye

Hayrani Eren Bostancı
0000-0001-8511-2316
Türkiye

Yusuf Tutar
0000-0003-2613-9644
Türkiye

Ahmet Koçak
0000-0002-2487-2431
Türkiye

Mustafa Yılmaz
0000-0003-2904-160X
Türkiye

Publication Date

December 27, 2022

Submission Date

September 10, 2022

Acceptance Date

December 10, 2022

Published in Issue

Year 2022 Volume: 43 Number: 4

DOI

https://doi.org/10.17776/csj.1173347

IZ

https://izlik.org/JA92RP66KY

Cite

RIS / Bibtex

APA

Işık, A., Uçar Çifçi, K., Bostancı, H. E., Tutar, Y., Koçak, A., & Yılmaz, M. (2022). Synthesis and Characterization of Novel Calix[4]arene Schiff Base Derivatives and Cytotoxicity Effect Evaluation on Cancer Cell Lines. Cumhuriyet Science Journal, 43(4), 629-633. https://doi.org/10.17776/csj.1173347

Cited By

Recent Advances in Calixarenes for the Detection of Metal Ions, Bioimaging Applications, and Anticancer Activities: A Comprehensive Review (2020–2024)

Critical Reviews in Analytical Chemistry

https://doi.org/10.1080/10408347.2024.2402820

Öz

Synthesis and Characterization of Novel Calix[4]arene Schiff Base Derivatives and Cytotoxicity Effect Evaluation on Cancer Cell Lines

Abstract

Keywords

Supporting Institution

Project Number

References

Details

Primary Language

Subjects

Journal Section

Authors

Publication Date

Submission Date

Acceptance Date

Published in Issue

DOI

IZ

Cite

Cited By

Recent Advances in Calixarenes for the Detection of Metal Ions, Bioimaging Applications, and Anticancer Activities: A Comprehensive Review (2020–2024)