Synthesis and cytotoxic activity evaluation of novel imidazopyridine carbohydrazide derivatives
Abstract Two series of novel imidazo[1,2-a]pyridine-2-carbohydrazide derivatives have been designed, synthesized, and evaluated for cytotoxic activity. Target compounds were designed in two series: aryl hydrazone derivatives that were devoid of triazole moiety (7a-e) and aryl triazole bearing group...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | BMC Chemistry |
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| Online Access: | https://doi.org/10.1186/s13065-023-01073-3 |
| _version_ | 1797363687402504192 |
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| author | Maryam Firouzi Zahra Haghighijoo Masoomeh Eskandari Maryam Mohabbati Ramin Miri Mohammad Hasan Jamei Alireza Poustforoosh Somayeh Nazari Omidreza Firuzi Mehdi Khoshneviszadeh Najmeh Edraki |
| author_facet | Maryam Firouzi Zahra Haghighijoo Masoomeh Eskandari Maryam Mohabbati Ramin Miri Mohammad Hasan Jamei Alireza Poustforoosh Somayeh Nazari Omidreza Firuzi Mehdi Khoshneviszadeh Najmeh Edraki |
| author_sort | Maryam Firouzi |
| collection | DOAJ |
| description | Abstract Two series of novel imidazo[1,2-a]pyridine-2-carbohydrazide derivatives have been designed, synthesized, and evaluated for cytotoxic activity. Target compounds were designed in two series: aryl hydrazone derivatives that were devoid of triazole moiety (7a-e) and aryl triazole bearing group (11a-e). In vitro cytotoxicity screening was carried out using MTT assay against three human cancer cells including breast cancer (MCF-7), colon cancer (HT-29), and leukemia (K562) cell lines as well as a non-cancer cell line (Vero). Compound 7d bearing 4-bromophenyl pendant from aryl hydrazone series exhibited the highest cytotoxic potential with IC50 values of 22.6 µM and 13.4 µM against MCF-7 and HT-29 cells, respectively, while it was not toxic towards non-cancer cells up to the concentration of 100 µM. Cell cycle analysis revealed that 7d increased the number of MCF-7 cells in the G0/G1 phase and also induced apoptosis in these cells as revealed by Hoechst 33,258 staining. The molecular mechanism contributing to the anti-proliferative effect of the most potent compound was investigated in silico using Super Pred software and introduced PDGFRA as a plausible target for 7d. Molecular docking and molecular dynamic studies demonstrated Lys627 and Asp836 as key residues interacting with the active compound. Overall, 7d could serve as a suitable candidate for further modifications as a lead anticancer structure. |
| first_indexed | 2024-03-08T16:24:33Z |
| format | Article |
| id | doaj.art-b3857a4241ff4145bf0fa7257831487f |
| institution | Directory Open Access Journal |
| issn | 2661-801X |
| language | English |
| last_indexed | 2024-03-08T16:24:33Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Chemistry |
| spelling | doaj.art-b3857a4241ff4145bf0fa7257831487f2024-01-07T12:06:55ZengBMCBMC Chemistry2661-801X2024-01-0118111610.1186/s13065-023-01073-3Synthesis and cytotoxic activity evaluation of novel imidazopyridine carbohydrazide derivativesMaryam Firouzi0Zahra Haghighijoo1Masoomeh Eskandari2Maryam Mohabbati3Ramin Miri4Mohammad Hasan Jamei5Alireza Poustforoosh6Somayeh Nazari7Omidreza Firuzi8Mehdi Khoshneviszadeh9Najmeh Edraki10Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical SciencesMedicinal and Natural Products Chemistry Research Center, Shiraz University of Medical SciencesMedicinal and Natural Products Chemistry Research Center, Shiraz University of Medical SciencesMedicinal and Natural Products Chemistry Research Center, Shiraz University of Medical SciencesMedicinal and Natural Products Chemistry Research Center, Shiraz University of Medical SciencesMedicinal and Natural Products Chemistry Research Center, Shiraz University of Medical SciencesMedicinal and Natural Products Chemistry Research Center, Shiraz University of Medical SciencesMedicinal and Natural Products Chemistry Research Center, Shiraz University of Medical SciencesMedicinal and Natural Products Chemistry Research Center, Shiraz University of Medical SciencesMedicinal and Natural Products Chemistry Research Center, Shiraz University of Medical SciencesMedicinal and Natural Products Chemistry Research Center, Shiraz University of Medical SciencesAbstract Two series of novel imidazo[1,2-a]pyridine-2-carbohydrazide derivatives have been designed, synthesized, and evaluated for cytotoxic activity. Target compounds were designed in two series: aryl hydrazone derivatives that were devoid of triazole moiety (7a-e) and aryl triazole bearing group (11a-e). In vitro cytotoxicity screening was carried out using MTT assay against three human cancer cells including breast cancer (MCF-7), colon cancer (HT-29), and leukemia (K562) cell lines as well as a non-cancer cell line (Vero). Compound 7d bearing 4-bromophenyl pendant from aryl hydrazone series exhibited the highest cytotoxic potential with IC50 values of 22.6 µM and 13.4 µM against MCF-7 and HT-29 cells, respectively, while it was not toxic towards non-cancer cells up to the concentration of 100 µM. Cell cycle analysis revealed that 7d increased the number of MCF-7 cells in the G0/G1 phase and also induced apoptosis in these cells as revealed by Hoechst 33,258 staining. The molecular mechanism contributing to the anti-proliferative effect of the most potent compound was investigated in silico using Super Pred software and introduced PDGFRA as a plausible target for 7d. Molecular docking and molecular dynamic studies demonstrated Lys627 and Asp836 as key residues interacting with the active compound. Overall, 7d could serve as a suitable candidate for further modifications as a lead anticancer structure.https://doi.org/10.1186/s13065-023-01073-3Imidazopyridine1,2,3-triazole ringCarbohydrazideCytotoxic activityMolecular dockingMolecular dynamics |
| spellingShingle | Maryam Firouzi Zahra Haghighijoo Masoomeh Eskandari Maryam Mohabbati Ramin Miri Mohammad Hasan Jamei Alireza Poustforoosh Somayeh Nazari Omidreza Firuzi Mehdi Khoshneviszadeh Najmeh Edraki Synthesis and cytotoxic activity evaluation of novel imidazopyridine carbohydrazide derivatives BMC Chemistry Imidazopyridine 1,2,3-triazole ring Carbohydrazide Cytotoxic activity Molecular docking Molecular dynamics |
| title | Synthesis and cytotoxic activity evaluation of novel imidazopyridine carbohydrazide derivatives |
| title_full | Synthesis and cytotoxic activity evaluation of novel imidazopyridine carbohydrazide derivatives |
| title_fullStr | Synthesis and cytotoxic activity evaluation of novel imidazopyridine carbohydrazide derivatives |
| title_full_unstemmed | Synthesis and cytotoxic activity evaluation of novel imidazopyridine carbohydrazide derivatives |
| title_short | Synthesis and cytotoxic activity evaluation of novel imidazopyridine carbohydrazide derivatives |
| title_sort | synthesis and cytotoxic activity evaluation of novel imidazopyridine carbohydrazide derivatives |
| topic | Imidazopyridine 1,2,3-triazole ring Carbohydrazide Cytotoxic activity Molecular docking Molecular dynamics |
| url | https://doi.org/10.1186/s13065-023-01073-3 |
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