Synthesis, molecular modeling, and biological evaluation of novel imatinib derivatives as
anticancer agents

NG, YUK YIN; Günay, Fulya; Balta, Sevcan; Turgut, Zuhal; Gunkara, Omer Tahir; Ulucan, Ozlem

doi:10.3906/kim-2107-23

Synthesis, molecular modeling, and biological evaluation of novel imatinib derivatives as anticancer agents

Fulya GÜNAY, (Yıldız Teknik Üniversitesi, Fen Edebiyat Fakültesi, Kimya Bölümü, İstanbul, Türkiye)

Sevcan BALTA, (Yıldız Teknik Üniversitesi, Fen Edebiyat Fakültesi, Kimya Bölümü, İstanbul, Türkiye)

Yuk Yin NG, (İstanbul Bilgi Üniversitesi, Mühendislik ve Doğa Bilimleri Fakültesi, Genetik ve Biyomühendislik Bölümü, İstanbul, Türkiye)

Özlem ULUCAN, (İstanbul Bilgi Üniversitesi, Mühendislik ve Doğa Bilimleri Fakültesi, Genetik ve Biyomühendislik Bölümü, İstanbul, Türkiye)

Zuhal TURGUT, (Yıldız Teknik Üniversitesi, Fen Edebiyat Fakültesi, Kimya Bölümü, İstanbul, Türkiye)

Ömer Tahir GÜNKARA (Yıldız Teknik Üniversitesi, Fen Edebiyat Fakültesi, Kimya Bölümü, İstanbul, Türkiye)

Turkish Journal of Chemistry

5 0

Yıl: 2022 Cilt: 46 Sayı: 1 Sayfa Aralığı: 86 - 102 Metin Dili: İngilizce DOI: 10.3906/kim-2107-23 İndeks Tarihi: 04-07-2022

Synthesis, molecular modeling, and biological evaluation of novel imatinib derivatives as anticancer agents

Öz:

Different derivatives of imatinib were synthesized by a 3-step reaction method. The structures of the new compounds were characterized by spectroscopic methods. For quantitative evaluation of the biological activity of the compounds, MTT assays were performed, where four BCR-ABL negative leukemic cell lines (Jurkat, Reh, Nalm-6 and Molt-4), one BCR-ABL positive cell line (K562), and one non-leukemic cell line (Hek293T) were incubated with various concentrations of the derivatives. Although imatinib was specifically designed for the BCR-ABL protein, our results showed that it was also effective on BCR-ABL negative cell lines except for Reh cell line. Compound 9 showed lowest I$C_{50}$ values against Nalm-6 cells as 1.639 µM, also the values of Compound 10 for each cell were very close to imatinib. Molecular docking simulations suggest that except for compound 6, the compounds prefer a DFG-out conformation of the ABL kinase domain. Among them, compound 10 has the highest affinity for ABL kinase domain that is close to the affinity of imatinib. The common rings between compound 10 and imatinib adopt exactly the same conformation and same type of interactions in the ATP binding site with the ABL kinase domain.

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

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APA	Günay F, Balta S, NG Y, Ulucan O, Turgut Z, Gunkara O (2022). Synthesis, molecular modeling, and biological evaluation of novel imatinib derivatives as anticancer agents. , 86 - 102. 10.3906/kim-2107-23
Chicago	Günay Fulya,Balta Sevcan,NG YUK YIN,Ulucan Ozlem,Turgut Zuhal,Gunkara Omer Tahir Synthesis, molecular modeling, and biological evaluation of novel imatinib derivatives as anticancer agents. (2022): 86 - 102. 10.3906/kim-2107-23
MLA	Günay Fulya,Balta Sevcan,NG YUK YIN,Ulucan Ozlem,Turgut Zuhal,Gunkara Omer Tahir Synthesis, molecular modeling, and biological evaluation of novel imatinib derivatives as anticancer agents. , 2022, ss.86 - 102. 10.3906/kim-2107-23
AMA	Günay F,Balta S,NG Y,Ulucan O,Turgut Z,Gunkara O Synthesis, molecular modeling, and biological evaluation of novel imatinib derivatives as anticancer agents. . 2022; 86 - 102. 10.3906/kim-2107-23
Vancouver	Günay F,Balta S,NG Y,Ulucan O,Turgut Z,Gunkara O Synthesis, molecular modeling, and biological evaluation of novel imatinib derivatives as anticancer agents. . 2022; 86 - 102. 10.3906/kim-2107-23
IEEE	Günay F,Balta S,NG Y,Ulucan O,Turgut Z,Gunkara O "Synthesis, molecular modeling, and biological evaluation of novel imatinib derivatives as anticancer agents." , ss.86 - 102, 2022. 10.3906/kim-2107-23
ISNAD	Günay, Fulya vd. "Synthesis, molecular modeling, and biological evaluation of novel imatinib derivatives as anticancer agents". (2022), 86-102. https://doi.org/10.3906/kim-2107-23

APA	Günay F, Balta S, NG Y, Ulucan O, Turgut Z, Gunkara O (2022). Synthesis, molecular modeling, and biological evaluation of novel imatinib derivatives as anticancer agents. Turkish Journal of Chemistry, 46(1), 86 - 102. 10.3906/kim-2107-23
Chicago	Günay Fulya,Balta Sevcan,NG YUK YIN,Ulucan Ozlem,Turgut Zuhal,Gunkara Omer Tahir Synthesis, molecular modeling, and biological evaluation of novel imatinib derivatives as anticancer agents. Turkish Journal of Chemistry 46, no.1 (2022): 86 - 102. 10.3906/kim-2107-23
MLA	Günay Fulya,Balta Sevcan,NG YUK YIN,Ulucan Ozlem,Turgut Zuhal,Gunkara Omer Tahir Synthesis, molecular modeling, and biological evaluation of novel imatinib derivatives as anticancer agents. Turkish Journal of Chemistry, vol.46, no.1, 2022, ss.86 - 102. 10.3906/kim-2107-23
AMA	Günay F,Balta S,NG Y,Ulucan O,Turgut Z,Gunkara O Synthesis, molecular modeling, and biological evaluation of novel imatinib derivatives as anticancer agents. Turkish Journal of Chemistry. 2022; 46(1): 86 - 102. 10.3906/kim-2107-23
Vancouver	Günay F,Balta S,NG Y,Ulucan O,Turgut Z,Gunkara O Synthesis, molecular modeling, and biological evaluation of novel imatinib derivatives as anticancer agents. Turkish Journal of Chemistry. 2022; 46(1): 86 - 102. 10.3906/kim-2107-23
IEEE	Günay F,Balta S,NG Y,Ulucan O,Turgut Z,Gunkara O "Synthesis, molecular modeling, and biological evaluation of novel imatinib derivatives as anticancer agents." Turkish Journal of Chemistry, 46, ss.86 - 102, 2022. 10.3906/kim-2107-23
ISNAD	Günay, Fulya vd. "Synthesis, molecular modeling, and biological evaluation of novel imatinib derivatives as anticancer agents". Turkish Journal of Chemistry 46/1 (2022), 86-102. https://doi.org/10.3906/kim-2107-23