Design, Synthesis, In Vitro Biological Activity Evaluation and Stabilized Nanostructured Lipid Carrier Formulation of Newly Synthesized Schiff Bases-Based TMP Moieties
A series of novel Schiff bases-based TMP moieties have been designed and synthesized as potential anticancer agents. The target Schiff bases were screened for their cytotoxic activity against the MDA-MB-231 breast cancer cell line. Most of the tested molecules revealed good cytotoxic activity, espec...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-05-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/6/679 |
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| author | Syed Nasir Abbas Bukhari Mohamed Y. Zakaria Muhammad Usman Munir Naveed Ahmad Mervat A Elsherif Rasha Emad Badr Ahmad Khalaf Hassan Ali H. Abu Almaaty Islam Zaki |
| author_facet | Syed Nasir Abbas Bukhari Mohamed Y. Zakaria Muhammad Usman Munir Naveed Ahmad Mervat A Elsherif Rasha Emad Badr Ahmad Khalaf Hassan Ali H. Abu Almaaty Islam Zaki |
| author_sort | Syed Nasir Abbas Bukhari |
| collection | DOAJ |
| description | A series of novel Schiff bases-based TMP moieties have been designed and synthesized as potential anticancer agents. The target Schiff bases were screened for their cytotoxic activity against the MDA-MB-231 breast cancer cell line. Most of the tested molecules revealed good cytotoxic activity, especially compounds <b>4h,</b> <b>4j</b> and <b>5d</b>. Being the most potent, compound <b>4h</b> showed good tubulin polymerization inhibition activity as revealed by immunofluorescence analysis and ELISA assay. Additionally, compound <b>4h</b> was screened for cell cycle disturbance and apoptosis induction. Pre-G1 apoptosis and cell growth halt at the G2/M phase were discovered to be caused by it. Moreover, compound <b>4h</b> induced apoptosis via p53 and Bax activation, as well as reduced the level of Bcl-2. Additionally, the most potent compound <b>4h</b> was lodged on nanostructured lipid carriers (NLCs). 2<sup>3</sup> full factorial design was involved to govern the influence of the fabrication variables on the in vitro characters of the casted NLCs. F3 was picked as the optimum formula exhibiting dominant desirability value 0.805, EE% 95.6 ± 2.4, PS 222.4 ±18.7, PDI 0.23 ± 0.05 and ZP −39.2 ± 3.9 Mv. Furthermore, F3 affirmed improved solubility and release over the drug suspension. In the comparative cytotoxic activity, F3 was capable of diminishing the IC<sub>50</sub> by around 2.15 times for pure <b>4h</b>, while nearly close to the IC<sub>50</sub> of the reference drug. Thus, NLCs could be a potential platform for boosted antitumor activity. |
| first_indexed | 2024-03-09T22:47:21Z |
| format | Article |
| id | doaj.art-5f60b901b9a84e34bec8f16399df0a20 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T22:47:21Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-5f60b901b9a84e34bec8f16399df0a202023-11-23T18:26:54ZengMDPI AGPharmaceuticals1424-82472022-05-0115667910.3390/ph15060679Design, Synthesis, In Vitro Biological Activity Evaluation and Stabilized Nanostructured Lipid Carrier Formulation of Newly Synthesized Schiff Bases-Based TMP MoietiesSyed Nasir Abbas Bukhari0Mohamed Y. Zakaria1Muhammad Usman Munir2Naveed Ahmad3Mervat A Elsherif4Rasha Emad Badr5Ahmad Khalaf Hassan6Ali H. Abu Almaaty7Islam Zaki8Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka 72388, Saudi ArabiaDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Port Said University, Port Said 42526, EgyptDepartment of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka 72388, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka 72388, Saudi ArabiaChemistry Department, College of Science, Jouf University, Sakaka 72388, Saudi ArabiaClinical and Chemical Pathology Department, Faculty of Medicine, Port Said University, Port Said 42526, EgyptZoology Department, Faculty of Science, Port Said University, Port Said 42526, EgyptZoology Department, Faculty of Science, Port Said University, Port Said 42526, EgyptPharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Port Said University, Port Said 42526, EgyptA series of novel Schiff bases-based TMP moieties have been designed and synthesized as potential anticancer agents. The target Schiff bases were screened for their cytotoxic activity against the MDA-MB-231 breast cancer cell line. Most of the tested molecules revealed good cytotoxic activity, especially compounds <b>4h,</b> <b>4j</b> and <b>5d</b>. Being the most potent, compound <b>4h</b> showed good tubulin polymerization inhibition activity as revealed by immunofluorescence analysis and ELISA assay. Additionally, compound <b>4h</b> was screened for cell cycle disturbance and apoptosis induction. Pre-G1 apoptosis and cell growth halt at the G2/M phase were discovered to be caused by it. Moreover, compound <b>4h</b> induced apoptosis via p53 and Bax activation, as well as reduced the level of Bcl-2. Additionally, the most potent compound <b>4h</b> was lodged on nanostructured lipid carriers (NLCs). 2<sup>3</sup> full factorial design was involved to govern the influence of the fabrication variables on the in vitro characters of the casted NLCs. F3 was picked as the optimum formula exhibiting dominant desirability value 0.805, EE% 95.6 ± 2.4, PS 222.4 ±18.7, PDI 0.23 ± 0.05 and ZP −39.2 ± 3.9 Mv. Furthermore, F3 affirmed improved solubility and release over the drug suspension. In the comparative cytotoxic activity, F3 was capable of diminishing the IC<sub>50</sub> by around 2.15 times for pure <b>4h</b>, while nearly close to the IC<sub>50</sub> of the reference drug. Thus, NLCs could be a potential platform for boosted antitumor activity.https://www.mdpi.com/1424-8247/15/6/679TMPSchiff basesynthesiscytotoxicitytubulincell cycle analysis |
| spellingShingle | Syed Nasir Abbas Bukhari Mohamed Y. Zakaria Muhammad Usman Munir Naveed Ahmad Mervat A Elsherif Rasha Emad Badr Ahmad Khalaf Hassan Ali H. Abu Almaaty Islam Zaki Design, Synthesis, In Vitro Biological Activity Evaluation and Stabilized Nanostructured Lipid Carrier Formulation of Newly Synthesized Schiff Bases-Based TMP Moieties Pharmaceuticals TMP Schiff base synthesis cytotoxicity tubulin cell cycle analysis |
| title | Design, Synthesis, In Vitro Biological Activity Evaluation and Stabilized Nanostructured Lipid Carrier Formulation of Newly Synthesized Schiff Bases-Based TMP Moieties |
| title_full | Design, Synthesis, In Vitro Biological Activity Evaluation and Stabilized Nanostructured Lipid Carrier Formulation of Newly Synthesized Schiff Bases-Based TMP Moieties |
| title_fullStr | Design, Synthesis, In Vitro Biological Activity Evaluation and Stabilized Nanostructured Lipid Carrier Formulation of Newly Synthesized Schiff Bases-Based TMP Moieties |
| title_full_unstemmed | Design, Synthesis, In Vitro Biological Activity Evaluation and Stabilized Nanostructured Lipid Carrier Formulation of Newly Synthesized Schiff Bases-Based TMP Moieties |
| title_short | Design, Synthesis, In Vitro Biological Activity Evaluation and Stabilized Nanostructured Lipid Carrier Formulation of Newly Synthesized Schiff Bases-Based TMP Moieties |
| title_sort | design synthesis in vitro biological activity evaluation and stabilized nanostructured lipid carrier formulation of newly synthesized schiff bases based tmp moieties |
| topic | TMP Schiff base synthesis cytotoxicity tubulin cell cycle analysis |
| url | https://www.mdpi.com/1424-8247/15/6/679 |
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