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A New Schiff Base Molecule Prepared from Pyrimidine-2-thione: Synthesis, Spectral Characterization, Cytotoxic Activity, DFT, and Molecular Docking Studies

Year 2022, Volume: 12 Issue: 1, 9 - 25, 30.06.2022
https://doi.org/10.37094/adyujsci.1020171

Abstract

Schiff base derivatives are some of the most widely used organic compounds for industrial purposes and they exhibit a broad range of biological activities. In this paper, a new Schiff base derivative (2) synthesized from the condensation reaction of 1-amino-5-benzoyl)-4- phenylpyrimidine-2(1H)-thione (1) with 2-chlorobenzaldehyde. The new compound was characterized by 1H, 13C NMR, and FT-IR. The biological activity property of this compound was tested against two different cancer cell lines and a healthy human cell line. The results demonstrate that molecule 2 has antiproliferative activity. In molecular modeling studies, the interaction site was examined using the epidermal growth factor receptor (EGFR) tyrosine kinase domain. Alignment in molecular docking, surface mapping binding, amino acids, and binding energy calculated. Glide score energy was found to be -9.820 kcal/mol and it predicted that the bonding interaction is strong. Theoretical calculations were made to compare the experimental and theoretical data. These calculations were performed on the 6–31 G* basis set using the Density Functional Theory (DFT) method and Becke-3-Parameter-Lee-Yang-Parr (B3LYP). Using this method, various parameters, such as frontier molecular orbitals, HOMO-LUMO energy levels, band gap, and chemical reactivity indices were found and interpreted.

Thanks

Burçin Türkmenoğlu would like to thank Erzincan Binali Yıldırım University, Basic Sciences Application and Research Center (EBYU-EUTAM) for the Schrödinger Maestro 2021- 2 program. Senem Akkoç would like to thank Suleyman Demirel University Research Fund (TSG-2021-8458) for financial support.

References

  • [1] Bogert, M.T., Beal, G.D., Researches on quinazolines (twenty-ninth paper). A further study of the stilbazoles, hydrazones and schiff bases of the 4-quinazolone group1, Journal of the American Chemical Society, 34, 516-524, 1912.
  • [2] Sumerford, W.T., Hartung, W.H., Jenkins, G.L., Some Schiff Bases with p- Aminothymol, Journal of the American Chemical Society, 62, 2082-2083, 1940.
  • [3] McIntire, F.C., Some Schiff bases of free amino acids, Journal of the American Chemical Society, 69, 1377-1380, 1947.
  • [4] Stephens, F.F., Heterocyclic compounds from Schiff's bases, Nature, 164, 243, 1949.
  • [5] Holly, F.W., Cope, A.C., Condensation products of aldehydes and ketones with o- aminobenzyl alcohol and o-hydroxybenzylamine, Journal of the American Chemical Society, 66, 1875-1879, 1944.
  • [6] Surrey, A.R., The preparation of 4-thiazolidones by the reaction of thioglycolic acid with Schiff bases, Journal of the American Chemical Society, 69, 2911-2912, 1947.
  • [7] Hodnett, E.M., Dunn, W.J., Structure-antitumor activity correlation of some Schiff bases, Journal of Medicinal Chemistry, 13, 768-770, 1970.
  • [8] Kaur, H., Lim, S.M., Ramasamy, K., Vasudevan, M., Shah, S.A.A., Narasimhan, B., Diazenyl schiff bases: Synthesis, spectral analysis, antimicrobial studies and cytotoxic activity on human colorectal carcinoma cell line (HCT-116), Arabian Journal of Chemistry, 13, 377-392, 2020.
  • [9] Ma, L.Y., Pang, L.P., Wang, B., Zhang, M., Hu, B., Xue, D.Q., Design and synthesis of novel 1,2,3-triazole-pyrimidine hybrids as potential anticancer agents, European Journal of Medicinal Chemistry, 86, 368-380, 2014.
  • [10] Rai, D., Chen W Fau - Tian, Y., Tian Y Fau - Chen, X., Chen X Fau - Zhan, P., Zhan P Fau - De Clercq, E., De Clercq E Fau - Pannecouque, C., Design, synthesis and biological evaluation of 3-benzyloxy-linked pyrimidinylphenylamine derivatives as potent HIV-1 NNRTIs, Bioorganic & Medicinal Chemistry, 21, 7398-7405, 2013.
  • [11] Ramiz, M.M.M., El-Sayed, W.A., El-Tantawy, A.I., Abdel-Rahman, A.A.H., Antimicrobial Activity of New 4,6-Disubstituted Pyrimidine, Pyrazoline, and Pyran Derivatives, Archives of Pharmacal Research, 33, 647-654, 2010.
  • [12] Hwang, J.Y., Windisch, M.P., Jo, S., Kim, K., Kong, S., Kim, H.C., Discovery and characterization of a novel 7-aminopyrazolo[1,5-a]pyrimidine analog as a potent hepatitis C virus inhibitor, Bioorganic & Medicinal Chemistry Letters, 22, 7297-7301, 2012.
  • [13] Gondkar, A.S., Deshmukh, V.K., Chaudhari, S.R., Synthesis, characterization and in- vitro anti-inflammatory activity of some substituted 1,2,3,4 tetrahydropyrimidine derivatives, Drug Invention Today, 5, 175-181, 2013.
  • [14] Onal, Z., Daylan, A.C., Cyclization reactions of 1-pyrimidinyl-3-arylthiourea derivatives with oxalyl dichlorideAsian Journal of Chemistry, 19, 1455-1460, 2007.
  • [15] Saracoglu, M., Kokbudak, Z., Yalcin, E., Kandemirli, F., Synthesis and Dft quantum chemical calculations of 2-oxopyrimidin-1(2h)-yl-urea and thiorea derivatives, Journal of The Chemical Society of Pakistan, 41, 841-858, 2019.
  • [16] Onal, Z., Ceran, H., Sahin, E., Synthesis of novel dihydropyrazolo[1,5-C]pyrimidin- 7(3h)-one/-thione derivatives, Heterocyclic Communications, 14, 245-250, 2008.
  • [17] Cimen, Z., Akkoc, S., Kokbudak, Z. Reactions of aminopyrimidine derivatives with chloroacetyl and isophthaloyl chlorides, Heteroatom Chemistry, 29, 2018.
  • [18] Aslan, H.G., Akkoc, S., Kokbudak, Z., Aydin, L., Synthesis, characterization, and antimicrobial and catalytic activity of a new Schiff base and its metal(II) complexes, Journal of the Iranian Chemical Society, 14, 2263-2273, 2017.
  • [19] Aslan, H.G., Akkoc, S., Kokbudak, Z., Anticancer activities of various new metal complexes prepared from a Schiff base on A549 cell line, Inorganic Chemistry Communications, 111, 2020
  • [20] Kokbudak, Z., Saracoglu, M., Akkoc, S., Cimen, Z., Yilmazer, M.I., Kandemirli, F., Synthesis, cytotoxic activity and quantum chemical calculations of new 7-thioxopyrazolo[1,5- f]pyrimidin-2-one derivatives. Journal of Molecular Structure, 1202, 2020.
  • [21] Kokbudak, Z., Aslan, H.G., Akkoc, S., New Schiff Bases Based on 1-Aminopyrimidin- 2-(1h)-One: Design, Synthesis, Characterization and Theoretical Calculations, Heterocycles, 100, 440-449, 2020.
  • [22] Elmaci, G., Duyar, H., Aydiner, B., Seferoglu, N., Naziri, M.A., Sahin, E., The syntheses, molecular structure analyses and DFT studies on new benzil monohydrazone based Schiff bases, Journal of Molecular Structure, 1162, 37-44, 2018.
  • [23] Elmaci, G., Duyar, H., Aydiner, B., Yahaya, I., Seferoglu, N., Sahin, E., Novel benzildihydrazone based Schiff bases: Syntheses, characterization, thermal properties, theoretical DFT calculations and biological activity studies, Journal of Molecular Structure, 1184, 271-280, 2019.
  • [24] Elmacı, G., Aktan, E., Seferoğlu, N., Hökelek, T., Seferoğlu, Z., Synthesis, molecular structure and computational study of (Z)-2-((E)-4-nitrobenzylidene) hydrazone)-1, 2- diphenylethan-1-one, Journal of Molecular Structure, 1099, 83-91, 2015.
  • [25] Antonello, A., Tarozzi, A., Morroni, F., Cavalli, A., Rosini, M., Hrelia, P., Multitarget- directed drug design strategy: A novel molecule designed to block epidermal growth factor receptor (EGFR) and to exert proapoptotic effects, Journal of Medicinal Chemistry, 49, 6642- 6645, 2006.
  • [26] Pawar, V.G., Sos, M.L., Rode, H.B., Rabiller, M., Heynck, S., van Otterlo, W.A.L., Synthesis and Biological Evaluation of 4-Anilinoquinolines as Potent Inhibitors of Epidermal Growth Factor Receptor, Journal of Medicinal Chemistry, 53, 2892-2901, 2010.
  • [27] Yu, H.Q., Li, Y.X., Ge, Y., Song, Z.D., Wang, C.Y., Huang, S.S., Novel 4- anilinoquinazoline derivatives featuring an 1-adamantyl moiety as potent EGFR inhibitors with enhanced activity against NSCLC cell lines, European Journal of Medicinal Chemistry, 110, 195- 203, 2016.
  • [28] Elbastawesy, M.A.I., Aly, A.A., Ramadan, M., Elshaier, Y.A.M.M., Youssif, B.G.M., Brown, A.B., Novel Pyrazoloquinolin-2-ones: Design, synthesis, docking studies, and biological evaluation as antiproliferative EGFR-TK inhibitors, Bioorganic Chemistry, 90, 103045, 2019.
Year 2022, Volume: 12 Issue: 1, 9 - 25, 30.06.2022
https://doi.org/10.37094/adyujsci.1020171

Abstract

References

  • [1] Bogert, M.T., Beal, G.D., Researches on quinazolines (twenty-ninth paper). A further study of the stilbazoles, hydrazones and schiff bases of the 4-quinazolone group1, Journal of the American Chemical Society, 34, 516-524, 1912.
  • [2] Sumerford, W.T., Hartung, W.H., Jenkins, G.L., Some Schiff Bases with p- Aminothymol, Journal of the American Chemical Society, 62, 2082-2083, 1940.
  • [3] McIntire, F.C., Some Schiff bases of free amino acids, Journal of the American Chemical Society, 69, 1377-1380, 1947.
  • [4] Stephens, F.F., Heterocyclic compounds from Schiff's bases, Nature, 164, 243, 1949.
  • [5] Holly, F.W., Cope, A.C., Condensation products of aldehydes and ketones with o- aminobenzyl alcohol and o-hydroxybenzylamine, Journal of the American Chemical Society, 66, 1875-1879, 1944.
  • [6] Surrey, A.R., The preparation of 4-thiazolidones by the reaction of thioglycolic acid with Schiff bases, Journal of the American Chemical Society, 69, 2911-2912, 1947.
  • [7] Hodnett, E.M., Dunn, W.J., Structure-antitumor activity correlation of some Schiff bases, Journal of Medicinal Chemistry, 13, 768-770, 1970.
  • [8] Kaur, H., Lim, S.M., Ramasamy, K., Vasudevan, M., Shah, S.A.A., Narasimhan, B., Diazenyl schiff bases: Synthesis, spectral analysis, antimicrobial studies and cytotoxic activity on human colorectal carcinoma cell line (HCT-116), Arabian Journal of Chemistry, 13, 377-392, 2020.
  • [9] Ma, L.Y., Pang, L.P., Wang, B., Zhang, M., Hu, B., Xue, D.Q., Design and synthesis of novel 1,2,3-triazole-pyrimidine hybrids as potential anticancer agents, European Journal of Medicinal Chemistry, 86, 368-380, 2014.
  • [10] Rai, D., Chen W Fau - Tian, Y., Tian Y Fau - Chen, X., Chen X Fau - Zhan, P., Zhan P Fau - De Clercq, E., De Clercq E Fau - Pannecouque, C., Design, synthesis and biological evaluation of 3-benzyloxy-linked pyrimidinylphenylamine derivatives as potent HIV-1 NNRTIs, Bioorganic & Medicinal Chemistry, 21, 7398-7405, 2013.
  • [11] Ramiz, M.M.M., El-Sayed, W.A., El-Tantawy, A.I., Abdel-Rahman, A.A.H., Antimicrobial Activity of New 4,6-Disubstituted Pyrimidine, Pyrazoline, and Pyran Derivatives, Archives of Pharmacal Research, 33, 647-654, 2010.
  • [12] Hwang, J.Y., Windisch, M.P., Jo, S., Kim, K., Kong, S., Kim, H.C., Discovery and characterization of a novel 7-aminopyrazolo[1,5-a]pyrimidine analog as a potent hepatitis C virus inhibitor, Bioorganic & Medicinal Chemistry Letters, 22, 7297-7301, 2012.
  • [13] Gondkar, A.S., Deshmukh, V.K., Chaudhari, S.R., Synthesis, characterization and in- vitro anti-inflammatory activity of some substituted 1,2,3,4 tetrahydropyrimidine derivatives, Drug Invention Today, 5, 175-181, 2013.
  • [14] Onal, Z., Daylan, A.C., Cyclization reactions of 1-pyrimidinyl-3-arylthiourea derivatives with oxalyl dichlorideAsian Journal of Chemistry, 19, 1455-1460, 2007.
  • [15] Saracoglu, M., Kokbudak, Z., Yalcin, E., Kandemirli, F., Synthesis and Dft quantum chemical calculations of 2-oxopyrimidin-1(2h)-yl-urea and thiorea derivatives, Journal of The Chemical Society of Pakistan, 41, 841-858, 2019.
  • [16] Onal, Z., Ceran, H., Sahin, E., Synthesis of novel dihydropyrazolo[1,5-C]pyrimidin- 7(3h)-one/-thione derivatives, Heterocyclic Communications, 14, 245-250, 2008.
  • [17] Cimen, Z., Akkoc, S., Kokbudak, Z. Reactions of aminopyrimidine derivatives with chloroacetyl and isophthaloyl chlorides, Heteroatom Chemistry, 29, 2018.
  • [18] Aslan, H.G., Akkoc, S., Kokbudak, Z., Aydin, L., Synthesis, characterization, and antimicrobial and catalytic activity of a new Schiff base and its metal(II) complexes, Journal of the Iranian Chemical Society, 14, 2263-2273, 2017.
  • [19] Aslan, H.G., Akkoc, S., Kokbudak, Z., Anticancer activities of various new metal complexes prepared from a Schiff base on A549 cell line, Inorganic Chemistry Communications, 111, 2020
  • [20] Kokbudak, Z., Saracoglu, M., Akkoc, S., Cimen, Z., Yilmazer, M.I., Kandemirli, F., Synthesis, cytotoxic activity and quantum chemical calculations of new 7-thioxopyrazolo[1,5- f]pyrimidin-2-one derivatives. Journal of Molecular Structure, 1202, 2020.
  • [21] Kokbudak, Z., Aslan, H.G., Akkoc, S., New Schiff Bases Based on 1-Aminopyrimidin- 2-(1h)-One: Design, Synthesis, Characterization and Theoretical Calculations, Heterocycles, 100, 440-449, 2020.
  • [22] Elmaci, G., Duyar, H., Aydiner, B., Seferoglu, N., Naziri, M.A., Sahin, E., The syntheses, molecular structure analyses and DFT studies on new benzil monohydrazone based Schiff bases, Journal of Molecular Structure, 1162, 37-44, 2018.
  • [23] Elmaci, G., Duyar, H., Aydiner, B., Yahaya, I., Seferoglu, N., Sahin, E., Novel benzildihydrazone based Schiff bases: Syntheses, characterization, thermal properties, theoretical DFT calculations and biological activity studies, Journal of Molecular Structure, 1184, 271-280, 2019.
  • [24] Elmacı, G., Aktan, E., Seferoğlu, N., Hökelek, T., Seferoğlu, Z., Synthesis, molecular structure and computational study of (Z)-2-((E)-4-nitrobenzylidene) hydrazone)-1, 2- diphenylethan-1-one, Journal of Molecular Structure, 1099, 83-91, 2015.
  • [25] Antonello, A., Tarozzi, A., Morroni, F., Cavalli, A., Rosini, M., Hrelia, P., Multitarget- directed drug design strategy: A novel molecule designed to block epidermal growth factor receptor (EGFR) and to exert proapoptotic effects, Journal of Medicinal Chemistry, 49, 6642- 6645, 2006.
  • [26] Pawar, V.G., Sos, M.L., Rode, H.B., Rabiller, M., Heynck, S., van Otterlo, W.A.L., Synthesis and Biological Evaluation of 4-Anilinoquinolines as Potent Inhibitors of Epidermal Growth Factor Receptor, Journal of Medicinal Chemistry, 53, 2892-2901, 2010.
  • [27] Yu, H.Q., Li, Y.X., Ge, Y., Song, Z.D., Wang, C.Y., Huang, S.S., Novel 4- anilinoquinazoline derivatives featuring an 1-adamantyl moiety as potent EGFR inhibitors with enhanced activity against NSCLC cell lines, European Journal of Medicinal Chemistry, 110, 195- 203, 2016.
  • [28] Elbastawesy, M.A.I., Aly, A.A., Ramadan, M., Elshaier, Y.A.M.M., Youssif, B.G.M., Brown, A.B., Novel Pyrazoloquinolin-2-ones: Design, synthesis, docking studies, and biological evaluation as antiproliferative EGFR-TK inhibitors, Bioorganic Chemistry, 90, 103045, 2019.
There are 28 citations in total.

Details

Primary Language English
Subjects Organic Chemistry
Journal Section Chemistry
Authors

Zülbiye Kökbudak 0000-0003-2413-9595

Burçin Türkmenoğlu 0000-0002-5770-0847

Senem Akkoç 0000-0002-1260-9425

Publication Date June 30, 2022
Submission Date November 7, 2021
Acceptance Date April 1, 2022
Published in Issue Year 2022 Volume: 12 Issue: 1

Cite

APA Kökbudak, Z., Türkmenoğlu, B., & Akkoç, S. (2022). A New Schiff Base Molecule Prepared from Pyrimidine-2-thione: Synthesis, Spectral Characterization, Cytotoxic Activity, DFT, and Molecular Docking Studies. Adıyaman University Journal of Science, 12(1), 9-25. https://doi.org/10.37094/adyujsci.1020171
AMA Kökbudak Z, Türkmenoğlu B, Akkoç S. A New Schiff Base Molecule Prepared from Pyrimidine-2-thione: Synthesis, Spectral Characterization, Cytotoxic Activity, DFT, and Molecular Docking Studies. ADYU J SCI. June 2022;12(1):9-25. doi:10.37094/adyujsci.1020171
Chicago Kökbudak, Zülbiye, Burçin Türkmenoğlu, and Senem Akkoç. “A New Schiff Base Molecule Prepared from Pyrimidine-2-Thione: Synthesis, Spectral Characterization, Cytotoxic Activity, DFT, and Molecular Docking Studies”. Adıyaman University Journal of Science 12, no. 1 (June 2022): 9-25. https://doi.org/10.37094/adyujsci.1020171.
EndNote Kökbudak Z, Türkmenoğlu B, Akkoç S (June 1, 2022) A New Schiff Base Molecule Prepared from Pyrimidine-2-thione: Synthesis, Spectral Characterization, Cytotoxic Activity, DFT, and Molecular Docking Studies. Adıyaman University Journal of Science 12 1 9–25.
IEEE Z. Kökbudak, B. Türkmenoğlu, and S. Akkoç, “A New Schiff Base Molecule Prepared from Pyrimidine-2-thione: Synthesis, Spectral Characterization, Cytotoxic Activity, DFT, and Molecular Docking Studies”, ADYU J SCI, vol. 12, no. 1, pp. 9–25, 2022, doi: 10.37094/adyujsci.1020171.
ISNAD Kökbudak, Zülbiye et al. “A New Schiff Base Molecule Prepared from Pyrimidine-2-Thione: Synthesis, Spectral Characterization, Cytotoxic Activity, DFT, and Molecular Docking Studies”. Adıyaman University Journal of Science 12/1 (June 2022), 9-25. https://doi.org/10.37094/adyujsci.1020171.
JAMA Kökbudak Z, Türkmenoğlu B, Akkoç S. A New Schiff Base Molecule Prepared from Pyrimidine-2-thione: Synthesis, Spectral Characterization, Cytotoxic Activity, DFT, and Molecular Docking Studies. ADYU J SCI. 2022;12:9–25.
MLA Kökbudak, Zülbiye et al. “A New Schiff Base Molecule Prepared from Pyrimidine-2-Thione: Synthesis, Spectral Characterization, Cytotoxic Activity, DFT, and Molecular Docking Studies”. Adıyaman University Journal of Science, vol. 12, no. 1, 2022, pp. 9-25, doi:10.37094/adyujsci.1020171.
Vancouver Kökbudak Z, Türkmenoğlu B, Akkoç S. A New Schiff Base Molecule Prepared from Pyrimidine-2-thione: Synthesis, Spectral Characterization, Cytotoxic Activity, DFT, and Molecular Docking Studies. ADYU J SCI. 2022;12(1):9-25.

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