2025_Synthesis Of Halogenated Ibuprofen And Aspirin Bearing Thiourea Derivatives For In-Vitro Cytotoxicity, Antibacterial And Molecular Docking Studies
| Format: | General Document |
|---|
| _version_ | 1860798337024786432 |
|---|---|
| building | INTELEK Repository |
| collection | Online Access |
| collectionurl | https://intelek.unisza.edu.my/intelek/pages/search.php?search=!collection3 |
| copyright | Copyright©PWB2025 |
| country | Malaysia |
| date | 2025-06-10 15:46 |
| format | General Document |
| id | 17330 |
| institution | UniSZA |
| originalfilename | 17330_bb177fae375fcc9.pdf |
| person | Azni Izwati |
| recordtype | oai_dc |
| resourceurl | https://intelek.unisza.edu.my/intelek/pages/view.php?ref=17330 |
| sourcemedia | Server storage Scanned document |
| spelling | 17330 https://intelek.unisza.edu.my/intelek/pages/view.php?ref=17330 https://intelek.unisza.edu.my/intelek/pages/search.php?search=!collection3 General Document Malaysia Library Staff (Top Management) Library Staff (Management) Library Staff (Support) Terengganu Faculty of Pharmacy English application/pdf 1.7 239 Microsoft® Word 2019 Server storage Scanned document UniSZA Private Access UniSZA Copyright©PWB2025 Organic Compounds Antibacterial Activity UniSZA Bioactive Compounds Dissertations-Academic Halogenated Ibuprofen Halogenated Aspirin Thiourea Derivatives Chemical Synthesis In-vitro Cytotoxicity Molecular Docking Drug Design Structure–activity Relationship (SAR) Pharmaceutical Chemistry Ibuprofen—Derivatives Aspirin—Derivatives Antibacterial Agents—Evaluation Organic Compounds—Synthesis Bioavailability—Testing 2025_Synthesis Of Halogenated Ibuprofen And Aspirin Bearing Thiourea Derivatives For In-Vitro Cytotoxicity, Antibacterial And Molecular Docking Studies In 2022, cancer had affected 20 million people globally, resulting in 9.7 million deaths, with breast and cervical cancers prevail most among Malaysian women. Bacterial infections have been reported to cause 1.27 million deaths worldwide. In Malaysia, over 200,000 people have been affected by the infections due to antibacterial resistance. These figures highlight the urgent need for new drugs with both anticancer and antibacterial properties. Ibuprofen and aspirin are commonly utilised as analgesic and antipyretic agent. However, they are also associated with gastrointestinal toxicity after long-term usage, largely due to carboxylic acid groups. The modification of ibuprofen and aspirin were attempted by replacing the carboxylic acid group with a thiourea moiety to improve their biological activities. The cytotoxicity of successfully modified compounds were evaluated using MTT assay against breast cancer (MCF-7) and cervical cancer (HeLa), then selected derivatives were tested against normal fibroblast cells (NIH/3T3). The antibacterial activities of all compounds were screened using disc diffusion assay and selected derivatives were analysed via minimum inhibition concentration (MIC) and minimum bactericidal concentration (MBC) assays using broth microdilution method against Staphylococcus aureus, Escherichia coli, Enterococcus faecalis and Pseudomonas aeruginosa. Then, molecular docking and ADME analysis of the synthesised compounds were conducted. The compounds synthesised from ibuprofen were unsuccessful, resulting in the formation of unexpected product. Using several approaches, halogenated aspirin bearing thiourea derivatives were successfully synthesised and characterised using spectroscopy and elemental analysis to investigate their biological activities. Most derivatives showed excellent cytotoxic effects than aspirin, especially 23p, which exhibited very strong activity against MCF-7 (IC50: 1.79 ± 0.28 μg/mL) and HeLa (IC50: 4.74 ± 0.47 μg/mL) cancer cells, surpassing aspirin with IC50: 17.96 ± 0.33 and 39.87 ± 1.80 μg/mL, respectively. Compound 23p also shows strong inhibition against normal cell, 3T3/NIH (IC50: 11.99 ± 0.39 μg/mL), comparable to aspirin (IC50: 15.27 ± 2.32 μg/mL) but less toxic than doxorubicin (IC50: 2.07 ± 0.14 μg/mL). The thiourea moiety may enhance protein penetration via hydrogen bonding, inhibiting cancer cells’ growth. Molecular docking of these derivatives showed binding affinities of < -7.0 kcal/mol against EGFR in cancer cells, better than aspirin but weaker than doxorubicin (-10.6 kcal/mol). Antibacterial study via disc diffusion revealed some derivatives displayed greater inhibition zones (12.0 ± 1.0 mm) against S. aureus than aspirin, with ampicillin showing 13.0 ± 0.0 mm. The derivatives contained C=S, C=O and NH groups which interacted effectively with the bacterial membrane, enhancing antibacterial activity. Selected derivatives were tested using MIC and MBC assay, revealing that dihalogenated derivatives were particularly effective against different bacteria. Molecular docking showed 23f and 23o exhibited better binding affinities at -8.4 and -7.9 kcal/mol compared to aspirin (-6.1 kcal/mol) and ampicillin (-7.8 kcal/mol) against CrtM protein of S. aureus. Both derivatives also showed better binding affinities at -8.6 and -8.5 kcal/mol compared to aspirin (-6.7 kcal/mol) and ampicillin (-6.5 kcal/mol) against DNA gyrase enzymes in E. coli. All derivatives complied with Lipinski’s rules, suggesting potential for drug development. Derivatives bearing dihalogen substituent exhibited the most promising to be developed as a new class of pharmaceutical agent. Azni Izwati 2025-06-10 15:46 uuid:DAA35B55-BE02-4224-A37F-E20D2E81F9B6 17330_bb177fae375fcc9.pdf Thesis |
| spellingShingle | 2025_Synthesis Of Halogenated Ibuprofen And Aspirin Bearing Thiourea Derivatives For In-Vitro Cytotoxicity, Antibacterial And Molecular Docking Studies |
| state | Terengganu |
| subject | Dissertations-Academic Ibuprofen—Derivatives Aspirin—Derivatives Antibacterial Agents—Evaluation Organic Compounds—Synthesis Bioavailability—Testing |
| summary | In 2022, cancer had affected 20 million people globally, resulting in 9.7 million deaths, with breast and cervical cancers prevail most among Malaysian women. Bacterial infections have been reported to cause 1.27 million deaths worldwide. In Malaysia, over 200,000 people have been affected by the infections due to antibacterial resistance. These figures highlight the urgent need for new drugs with both anticancer and antibacterial properties. Ibuprofen and aspirin are commonly utilised as analgesic and antipyretic agent. However, they are also associated with gastrointestinal toxicity after long-term usage, largely due to carboxylic acid groups. The modification of ibuprofen and aspirin were attempted by replacing the carboxylic acid group with a thiourea moiety to improve their biological activities. The cytotoxicity of successfully modified compounds were evaluated using MTT assay against breast cancer (MCF-7) and cervical cancer (HeLa), then selected derivatives were tested against normal fibroblast cells (NIH/3T3). The antibacterial activities of all compounds were screened using disc diffusion assay and selected derivatives were analysed via minimum inhibition concentration (MIC) and minimum bactericidal concentration (MBC) assays using broth microdilution method against Staphylococcus aureus, Escherichia coli, Enterococcus faecalis and Pseudomonas aeruginosa. Then, molecular docking and ADME analysis of the synthesised compounds were conducted. The compounds synthesised from ibuprofen were unsuccessful, resulting in the formation of unexpected product. Using several approaches, halogenated aspirin bearing thiourea derivatives were successfully synthesised and characterised using spectroscopy and elemental analysis to investigate their biological activities. Most derivatives showed excellent cytotoxic effects than aspirin, especially 23p, which exhibited very strong activity against MCF-7 (IC50: 1.79 ± 0.28 μg/mL) and HeLa (IC50: 4.74 ± 0.47 μg/mL) cancer cells, surpassing aspirin with IC50: 17.96 ± 0.33 and 39.87 ± 1.80 μg/mL, respectively. Compound 23p also shows strong inhibition against normal cell, 3T3/NIH (IC50: 11.99 ± 0.39 μg/mL), comparable to aspirin (IC50: 15.27 ± 2.32 μg/mL) but less toxic than doxorubicin (IC50: 2.07 ± 0.14 μg/mL). The thiourea moiety may enhance protein penetration via hydrogen bonding, inhibiting cancer cells’ growth. Molecular docking of these derivatives showed binding affinities of < -7.0 kcal/mol against EGFR in cancer cells, better than aspirin but weaker than doxorubicin (-10.6 kcal/mol). Antibacterial study via disc diffusion revealed some derivatives displayed greater inhibition zones (12.0 ± 1.0 mm) against S. aureus than aspirin, with ampicillin showing 13.0 ± 0.0 mm. The derivatives contained C=S, C=O and NH groups which interacted effectively with the bacterial membrane, enhancing antibacterial activity. Selected derivatives were tested using MIC and MBC assay, revealing that dihalogenated derivatives were particularly effective against different bacteria. Molecular docking showed 23f and 23o exhibited better binding affinities at -8.4 and -7.9 kcal/mol compared to aspirin (-6.1 kcal/mol) and ampicillin (-7.8 kcal/mol) against CrtM protein of S. aureus. Both derivatives also showed better binding affinities at -8.6 and -8.5 kcal/mol compared to aspirin (-6.7 kcal/mol) and ampicillin (-6.5 kcal/mol) against DNA gyrase enzymes in E. coli. All derivatives complied with Lipinski’s rules, suggesting potential for drug development. Derivatives bearing dihalogen substituent exhibited the most promising to be developed as a new class of pharmaceutical agent. |
| title | 2025_Synthesis Of Halogenated Ibuprofen And Aspirin Bearing Thiourea Derivatives For In-Vitro Cytotoxicity, Antibacterial And Molecular Docking Studies |
| title_full | 2025_Synthesis Of Halogenated Ibuprofen And Aspirin Bearing Thiourea Derivatives For In-Vitro Cytotoxicity, Antibacterial And Molecular Docking Studies |
| title_fullStr | 2025_Synthesis Of Halogenated Ibuprofen And Aspirin Bearing Thiourea Derivatives For In-Vitro Cytotoxicity, Antibacterial And Molecular Docking Studies |
| title_full_unstemmed | 2025_Synthesis Of Halogenated Ibuprofen And Aspirin Bearing Thiourea Derivatives For In-Vitro Cytotoxicity, Antibacterial And Molecular Docking Studies |
| title_short | 2025_Synthesis Of Halogenated Ibuprofen And Aspirin Bearing Thiourea Derivatives For In-Vitro Cytotoxicity, Antibacterial And Molecular Docking Studies |
| title_sort | 2025_synthesis of halogenated ibuprofen and aspirin bearing thiourea derivatives for in-vitro cytotoxicity, antibacterial and molecular docking studies |