Design and synthesis of thiazolidine-2,4-diones hybrids with 1,2-dihydroquinolones and 2-oxindoles as potential VEGFR-2 inhibitors: in-vitro anticancer evaluation and in-silico studies
A thiazolidine-2,4-dione nucleus was molecularly hybridised with the effective antitumor moieties; 2-oxo-1,2-dihydroquinoline and 2-oxoindoline to obtain new hybrids with potential activity against VEGFR-2. The cytotoxic effects of the synthesised derivatives against Caco-2, HepG-2, and MDA-MB-231 c...
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Taylor & Francis Group
2022-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2022.2085693 |
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| author | Mohammed S. Taghour Hazem Elkady Wagdy M. Eldehna Nehal M. El-Deeb Ahmed M. Kenawy Eslam B. Elkaeed Aisha A. Alsfouk Mohamed S. Alesawy Ahmed M. Metwaly Ibrahim. H. Eissa |
| author_facet | Mohammed S. Taghour Hazem Elkady Wagdy M. Eldehna Nehal M. El-Deeb Ahmed M. Kenawy Eslam B. Elkaeed Aisha A. Alsfouk Mohamed S. Alesawy Ahmed M. Metwaly Ibrahim. H. Eissa |
| author_sort | Mohammed S. Taghour |
| collection | DOAJ |
| description | A thiazolidine-2,4-dione nucleus was molecularly hybridised with the effective antitumor moieties; 2-oxo-1,2-dihydroquinoline and 2-oxoindoline to obtain new hybrids with potential activity against VEGFR-2. The cytotoxic effects of the synthesised derivatives against Caco-2, HepG-2, and MDA-MB-231 cell lines were investigated. Compound 12a was found to be the most potent candidate against the investigated cell lines with IC50 values of 2, 10, and 40 µM, respectively. Furthermore, the synthesised derivatives were tested in vitro for their VEGFR-2 inhibitory activity showing strong inhibition. Moreover, an in vitro viability study against Vero non-cancerous cell line was investigated and the results reflected a high safety profile of all tested compounds. Compound 12a was further investigated for its apoptotic behaviour by assessing the gene expression of four genes (Bcl2, Bcl-xl, TGF, and Survivin). Molecular dynamic simulations authenticated the high affinity, accurate binding, and perfect dynamics of compound 12a against VEGFR-2. |
| format | Article |
| id | doaj-art-6a1211054d8142c2aa418c8ca9a95338 |
| institution | DOAJ |
| issn | 1475-6366 1475-6374 |
| language | English |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj-art-6a1211054d8142c2aa418c8ca9a953382025-08-20T03:22:19ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742022-12-013711903191710.1080/14756366.2022.2085693Design and synthesis of thiazolidine-2,4-diones hybrids with 1,2-dihydroquinolones and 2-oxindoles as potential VEGFR-2 inhibitors: in-vitro anticancer evaluation and in-silico studiesMohammed S. Taghour0Hazem Elkady1Wagdy M. Eldehna2Nehal M. El-Deeb3Ahmed M. Kenawy4Eslam B. Elkaeed5Aisha A. Alsfouk6Mohamed S. Alesawy7Ahmed M. Metwaly8Ibrahim. H. Eissa9Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, EgyptPharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, EgyptDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, EgyptBiopharmaceutical Products Research Department, Genetic Engineering and Biotechnology Research Institute, City of Scientific Research and Technological Applications (SRTA-City), Alexandria, EgyptNucleic Acids Research Department, Genetic Engineering and Biotechnology Research Institute, City of Scientific Research and Technological Applications (SRTA-City), Alexandria, EgyptDepartment of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, Riyadh, Saudi ArabiaDepartment of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh, Saudi ArabiaPharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, EgyptBiopharmaceutical Products Research Department, Genetic Engineering and Biotechnology Research Institute, City of Scientific Research and Technological Applications (SRTA-City), Alexandria, EgyptPharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, EgyptA thiazolidine-2,4-dione nucleus was molecularly hybridised with the effective antitumor moieties; 2-oxo-1,2-dihydroquinoline and 2-oxoindoline to obtain new hybrids with potential activity against VEGFR-2. The cytotoxic effects of the synthesised derivatives against Caco-2, HepG-2, and MDA-MB-231 cell lines were investigated. Compound 12a was found to be the most potent candidate against the investigated cell lines with IC50 values of 2, 10, and 40 µM, respectively. Furthermore, the synthesised derivatives were tested in vitro for their VEGFR-2 inhibitory activity showing strong inhibition. Moreover, an in vitro viability study against Vero non-cancerous cell line was investigated and the results reflected a high safety profile of all tested compounds. Compound 12a was further investigated for its apoptotic behaviour by assessing the gene expression of four genes (Bcl2, Bcl-xl, TGF, and Survivin). Molecular dynamic simulations authenticated the high affinity, accurate binding, and perfect dynamics of compound 12a against VEGFR-2.https://www.tandfonline.com/doi/10.1080/14756366.2022.2085693ApoptosisanticancerVEGFR-2 inhibitors2-Oxo-1,2-dihydroquinolineThiazolidine-2,4-dione2-Oxoindoline |
| spellingShingle | Mohammed S. Taghour Hazem Elkady Wagdy M. Eldehna Nehal M. El-Deeb Ahmed M. Kenawy Eslam B. Elkaeed Aisha A. Alsfouk Mohamed S. Alesawy Ahmed M. Metwaly Ibrahim. H. Eissa Design and synthesis of thiazolidine-2,4-diones hybrids with 1,2-dihydroquinolones and 2-oxindoles as potential VEGFR-2 inhibitors: in-vitro anticancer evaluation and in-silico studies Journal of Enzyme Inhibition and Medicinal Chemistry Apoptosis anticancer VEGFR-2 inhibitors 2-Oxo-1,2-dihydroquinoline Thiazolidine-2,4-dione 2-Oxoindoline |
| title | Design and synthesis of thiazolidine-2,4-diones hybrids with 1,2-dihydroquinolones and 2-oxindoles as potential VEGFR-2 inhibitors: in-vitro anticancer evaluation and in-silico studies |
| title_full | Design and synthesis of thiazolidine-2,4-diones hybrids with 1,2-dihydroquinolones and 2-oxindoles as potential VEGFR-2 inhibitors: in-vitro anticancer evaluation and in-silico studies |
| title_fullStr | Design and synthesis of thiazolidine-2,4-diones hybrids with 1,2-dihydroquinolones and 2-oxindoles as potential VEGFR-2 inhibitors: in-vitro anticancer evaluation and in-silico studies |
| title_full_unstemmed | Design and synthesis of thiazolidine-2,4-diones hybrids with 1,2-dihydroquinolones and 2-oxindoles as potential VEGFR-2 inhibitors: in-vitro anticancer evaluation and in-silico studies |
| title_short | Design and synthesis of thiazolidine-2,4-diones hybrids with 1,2-dihydroquinolones and 2-oxindoles as potential VEGFR-2 inhibitors: in-vitro anticancer evaluation and in-silico studies |
| title_sort | design and synthesis of thiazolidine 2 4 diones hybrids with 1 2 dihydroquinolones and 2 oxindoles as potential vegfr 2 inhibitors in vitro anticancer evaluation and in silico studies |
| topic | Apoptosis anticancer VEGFR-2 inhibitors 2-Oxo-1,2-dihydroquinoline Thiazolidine-2,4-dione 2-Oxoindoline |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2022.2085693 |
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