1,3,4-Oxadiazole-naphthalene hybrids as potential VEGFR-2 inhibitors: design, synthesis, antiproliferative activity, apoptotic effect, and in silico studies
In the current work, some 1,3,4-oxadiazole-naphthalene hybrids were designed and synthesised as VEGFR-2 inhibitors. The synthesised compounds were evaluated in vitro for their antiproliferative activity against two human cancer cell lines namely, HepG-2 and MCF-7. Compounds that exhibited promising...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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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: | http://dx.doi.org/10.1080/14756366.2021.2015342 |
| _version_ | 1798019684271915008 |
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| author | Mohamed Hagras Marwa A. Saleh Rogy R. Ezz Eldin Abdelrahman A. Abuelkhir Emad Gamil Khidr Ahmed A. El-Husseiny Hesham A. El-Mahdy Eslam B. Elkaeed Ibrahim H. Eissa |
| author_facet | Mohamed Hagras Marwa A. Saleh Rogy R. Ezz Eldin Abdelrahman A. Abuelkhir Emad Gamil Khidr Ahmed A. El-Husseiny Hesham A. El-Mahdy Eslam B. Elkaeed Ibrahim H. Eissa |
| author_sort | Mohamed Hagras |
| collection | DOAJ |
| description | In the current work, some 1,3,4-oxadiazole-naphthalene hybrids were designed and synthesised as VEGFR-2 inhibitors. The synthesised compounds were evaluated in vitro for their antiproliferative activity against two human cancer cell lines namely, HepG-2 and MCF-7. Compounds that exhibited promising cytotoxicity (5, 8, 15, 16, 17, and 18) were further evaluated for their VEGFR-2 inhibitory activities. Compound 5 showed good antiproliferative activity against both cell lines and inhibitory effect on VEGFR-2. Besides, it induced apoptosis by 22.86% compared to 0.51% in the control (HepG2) cells. This apoptotic effect was supported by a 5.61-fold increase in the level of caspase-3 compared to the control cells. Moreover, it arrested the HepG2 cell growth mostly at the Pre-G1 phase. Several in silico studies were performed including docking, ADMET, and toxicity studies to predict binding mode against VEGFR-2 and to anticipate pharmacokinetic, drug-likeness, and toxicity of the synthesised compounds. |
| first_indexed | 2024-04-11T16:44:52Z |
| format | Article |
| id | doaj.art-428f05a2945c4f5b90792359899b4312 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-04-11T16:44:52Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-428f05a2945c4f5b90792359899b43122022-12-22T04:13:35ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742022-12-0137138640210.1080/14756366.2021.201534220153421,3,4-Oxadiazole-naphthalene hybrids as potential VEGFR-2 inhibitors: design, synthesis, antiproliferative activity, apoptotic effect, and in silico studiesMohamed Hagras0Marwa A. Saleh1Rogy R. Ezz Eldin2Abdelrahman A. Abuelkhir3Emad Gamil Khidr4Ahmed A. El-Husseiny5Hesham A. El-Mahdy6Eslam B. Elkaeed7Ibrahim H. Eissa8Pharmaceutical Organic Chemistry, Faculty of Pharmacy (Boys), Al-Azhar UniversityPharmaceutical Organic Chemistry, Faculty of Pharmacy (Girls), Al-Azhar UniversityDepartment of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Port Said UniversityPharmaceutical Organic Chemistry, Faculty of Pharmacy (Boys), Al-Azhar UniversityBiochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar UniversityBiochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar UniversityBiochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar UniversityDepartment of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa UniversityPharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar UniversityIn the current work, some 1,3,4-oxadiazole-naphthalene hybrids were designed and synthesised as VEGFR-2 inhibitors. The synthesised compounds were evaluated in vitro for their antiproliferative activity against two human cancer cell lines namely, HepG-2 and MCF-7. Compounds that exhibited promising cytotoxicity (5, 8, 15, 16, 17, and 18) were further evaluated for their VEGFR-2 inhibitory activities. Compound 5 showed good antiproliferative activity against both cell lines and inhibitory effect on VEGFR-2. Besides, it induced apoptosis by 22.86% compared to 0.51% in the control (HepG2) cells. This apoptotic effect was supported by a 5.61-fold increase in the level of caspase-3 compared to the control cells. Moreover, it arrested the HepG2 cell growth mostly at the Pre-G1 phase. Several in silico studies were performed including docking, ADMET, and toxicity studies to predict binding mode against VEGFR-2 and to anticipate pharmacokinetic, drug-likeness, and toxicity of the synthesised compounds.http://dx.doi.org/10.1080/14756366.2021.2015342anticancerapoptosisdocking1,3,4-oxadiazolevegfr-2 inhibitors |
| spellingShingle | Mohamed Hagras Marwa A. Saleh Rogy R. Ezz Eldin Abdelrahman A. Abuelkhir Emad Gamil Khidr Ahmed A. El-Husseiny Hesham A. El-Mahdy Eslam B. Elkaeed Ibrahim H. Eissa 1,3,4-Oxadiazole-naphthalene hybrids as potential VEGFR-2 inhibitors: design, synthesis, antiproliferative activity, apoptotic effect, and in silico studies Journal of Enzyme Inhibition and Medicinal Chemistry anticancer apoptosis docking 1,3,4-oxadiazole vegfr-2 inhibitors |
| title | 1,3,4-Oxadiazole-naphthalene hybrids as potential VEGFR-2 inhibitors: design, synthesis, antiproliferative activity, apoptotic effect, and in silico studies |
| title_full | 1,3,4-Oxadiazole-naphthalene hybrids as potential VEGFR-2 inhibitors: design, synthesis, antiproliferative activity, apoptotic effect, and in silico studies |
| title_fullStr | 1,3,4-Oxadiazole-naphthalene hybrids as potential VEGFR-2 inhibitors: design, synthesis, antiproliferative activity, apoptotic effect, and in silico studies |
| title_full_unstemmed | 1,3,4-Oxadiazole-naphthalene hybrids as potential VEGFR-2 inhibitors: design, synthesis, antiproliferative activity, apoptotic effect, and in silico studies |
| title_short | 1,3,4-Oxadiazole-naphthalene hybrids as potential VEGFR-2 inhibitors: design, synthesis, antiproliferative activity, apoptotic effect, and in silico studies |
| title_sort | 1 3 4 oxadiazole naphthalene hybrids as potential vegfr 2 inhibitors design synthesis antiproliferative activity apoptotic effect and in silico studies |
| topic | anticancer apoptosis docking 1,3,4-oxadiazole vegfr-2 inhibitors |
| url | http://dx.doi.org/10.1080/14756366.2021.2015342 |
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