Indole-based hydrazone derivatives: Synthesis, cytotoxicity assessment, and molecular modeling studies
Нема приказа
Аутори
Keskin, SelbiDogan, Sengul Dilem
Gunduz, Miyase Gozde
Aleksić, Ivana
Vojnović, Sandra
Lazić, Jelena
Nikodinović-Runić, Jasmina
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
In the present study, we report the synthesis, cytotoxicity determination and molecular modeling studies of twelve novel indole-based hydrazone derivatives ( IH1 - IH12 ). To obtain the target molecules, initially, 1 H -indole-2-carboxylic acid and ethanol were heated in the presence of an acid catalyst to yield ethyl 1 H -indole-2-carboxylate. Following the hydrazinolyzation of the ester moiety, the resulting compound, 1 H -indole-2-carbohydrazide reacted with appropriate benzaldehyde derivatives to obtain IH1 - IH12 . The proposed chemical structures of all compounds were confirmed by their 1 H NMR, 13 C NMR, IR, and HRMS data. Additionally, the configuration of C = N bond in IH8 was determined as ( E ) by applying 2D NMR technique, NOESY. Subsequently, the compounds were tested against both colon cancer (HCT116) and lung cancer (A549), as well as healthy lung fibroblast (MRC-5) cell lines to determine their potential as anticancer agents and their selectivity indexes (SI). Based on ...the obtained data from the antiproliferative MTT assay, HCT116 cell line was more sensitive to our molecules compared to A549. Furthermore, lipophilic halogens were preferable substituents on the phenyl ring for the selective toxicity against cancer cell lines. Drug-likeness analysis carried out by calculating important physicochemical properties of IH1 - IH12 confirmed that they all obey Lipinski's rule of five. Finally, hypoxia inducible factor (HIF)-1 alpha was suggested as the potential biological target of the compounds through molecular docking studies.
Кључне речи:
N-acylhydrazone / Molecular hybridization / Drug-likeness / Docking / Antiproliferative / AnticancerИзвор:
Journal of Molecular Structure, 2022, 1270Издавач:
- Elsevier, Amsterdam
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200042 (Универзитет у Београду, Институт за молекуларну генетику и генетичко инжењерство) (RS-MESTD-inst-2020-200042)
DOI: 10.1016/j.molstruc.2022.133936
ISSN: 0022-2860
WoS: 000860323800012
Scopus: 2-s2.0-85136590874
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Keskin, Selbi AU - Dogan, Sengul Dilem AU - Gunduz, Miyase Gozde AU - Aleksić, Ivana AU - Vojnović, Sandra AU - Lazić, Jelena AU - Nikodinović-Runić, Jasmina PY - 2022 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1514 AB - In the present study, we report the synthesis, cytotoxicity determination and molecular modeling studies of twelve novel indole-based hydrazone derivatives ( IH1 - IH12 ). To obtain the target molecules, initially, 1 H -indole-2-carboxylic acid and ethanol were heated in the presence of an acid catalyst to yield ethyl 1 H -indole-2-carboxylate. Following the hydrazinolyzation of the ester moiety, the resulting compound, 1 H -indole-2-carbohydrazide reacted with appropriate benzaldehyde derivatives to obtain IH1 - IH12 . The proposed chemical structures of all compounds were confirmed by their 1 H NMR, 13 C NMR, IR, and HRMS data. Additionally, the configuration of C = N bond in IH8 was determined as ( E ) by applying 2D NMR technique, NOESY. Subsequently, the compounds were tested against both colon cancer (HCT116) and lung cancer (A549), as well as healthy lung fibroblast (MRC-5) cell lines to determine their potential as anticancer agents and their selectivity indexes (SI). Based on the obtained data from the antiproliferative MTT assay, HCT116 cell line was more sensitive to our molecules compared to A549. Furthermore, lipophilic halogens were preferable substituents on the phenyl ring for the selective toxicity against cancer cell lines. Drug-likeness analysis carried out by calculating important physicochemical properties of IH1 - IH12 confirmed that they all obey Lipinski's rule of five. Finally, hypoxia inducible factor (HIF)-1 alpha was suggested as the potential biological target of the compounds through molecular docking studies. PB - Elsevier, Amsterdam T2 - Journal of Molecular Structure T1 - Indole-based hydrazone derivatives: Synthesis, cytotoxicity assessment, and molecular modeling studies VL - 1270 DO - 10.1016/j.molstruc.2022.133936 ER -
@article{ author = "Keskin, Selbi and Dogan, Sengul Dilem and Gunduz, Miyase Gozde and Aleksić, Ivana and Vojnović, Sandra and Lazić, Jelena and Nikodinović-Runić, Jasmina", year = "2022", abstract = "In the present study, we report the synthesis, cytotoxicity determination and molecular modeling studies of twelve novel indole-based hydrazone derivatives ( IH1 - IH12 ). To obtain the target molecules, initially, 1 H -indole-2-carboxylic acid and ethanol were heated in the presence of an acid catalyst to yield ethyl 1 H -indole-2-carboxylate. Following the hydrazinolyzation of the ester moiety, the resulting compound, 1 H -indole-2-carbohydrazide reacted with appropriate benzaldehyde derivatives to obtain IH1 - IH12 . The proposed chemical structures of all compounds were confirmed by their 1 H NMR, 13 C NMR, IR, and HRMS data. Additionally, the configuration of C = N bond in IH8 was determined as ( E ) by applying 2D NMR technique, NOESY. Subsequently, the compounds were tested against both colon cancer (HCT116) and lung cancer (A549), as well as healthy lung fibroblast (MRC-5) cell lines to determine their potential as anticancer agents and their selectivity indexes (SI). Based on the obtained data from the antiproliferative MTT assay, HCT116 cell line was more sensitive to our molecules compared to A549. Furthermore, lipophilic halogens were preferable substituents on the phenyl ring for the selective toxicity against cancer cell lines. Drug-likeness analysis carried out by calculating important physicochemical properties of IH1 - IH12 confirmed that they all obey Lipinski's rule of five. Finally, hypoxia inducible factor (HIF)-1 alpha was suggested as the potential biological target of the compounds through molecular docking studies.", publisher = "Elsevier, Amsterdam", journal = "Journal of Molecular Structure", title = "Indole-based hydrazone derivatives: Synthesis, cytotoxicity assessment, and molecular modeling studies", volume = "1270", doi = "10.1016/j.molstruc.2022.133936" }
Keskin, S., Dogan, S. D., Gunduz, M. G., Aleksić, I., Vojnović, S., Lazić, J.,& Nikodinović-Runić, J.. (2022). Indole-based hydrazone derivatives: Synthesis, cytotoxicity assessment, and molecular modeling studies. in Journal of Molecular Structure Elsevier, Amsterdam., 1270. https://doi.org/10.1016/j.molstruc.2022.133936
Keskin S, Dogan SD, Gunduz MG, Aleksić I, Vojnović S, Lazić J, Nikodinović-Runić J. Indole-based hydrazone derivatives: Synthesis, cytotoxicity assessment, and molecular modeling studies. in Journal of Molecular Structure. 2022;1270. doi:10.1016/j.molstruc.2022.133936 .
Keskin, Selbi, Dogan, Sengul Dilem, Gunduz, Miyase Gozde, Aleksić, Ivana, Vojnović, Sandra, Lazić, Jelena, Nikodinović-Runić, Jasmina, "Indole-based hydrazone derivatives: Synthesis, cytotoxicity assessment, and molecular modeling studies" in Journal of Molecular Structure, 1270 (2022), https://doi.org/10.1016/j.molstruc.2022.133936 . .