In Vitro α-Glucosidase and α-Amylase Inhibition, Cytotoxicity and Free Radical Scavenging Profiling of the 6-Halogeno and Mixed 6,8-Dihalogenated 2-Aryl-4-methyl-1,2-dihydroquinazoline 3-Oxides
Series of the 6-bromo/iodo substituted 2-aryl-4-methyl-1,2-dihydroquinazoline-3-oxides and their mixed 6,8-dihalogenated (Br/I and I/Br) derivatives were evaluated for inhibitory properties against α-glucosidase and/or α-amylase activities and for cytotoxicity against breast (MCF-7) and lung (A549)...
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MDPI AG
2023-11-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/12/11/1971 |
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| author | Nontokozo M. Magwaza Garland K. More Samantha Gildenhuys Malose J. Mphahlele |
| author_facet | Nontokozo M. Magwaza Garland K. More Samantha Gildenhuys Malose J. Mphahlele |
| author_sort | Nontokozo M. Magwaza |
| collection | DOAJ |
| description | Series of the 6-bromo/iodo substituted 2-aryl-4-methyl-1,2-dihydroquinazoline-3-oxides and their mixed 6,8-dihalogenated (Br/I and I/Br) derivatives were evaluated for inhibitory properties against α-glucosidase and/or α-amylase activities and for cytotoxicity against breast (MCF-7) and lung (A549) cancer cell lines. The 6-bromo-2-phenyl substituted <b>3a</b> and its corresponding 6-bromo-8-iodo-2-phenyl-substituted derivative <b>3i</b> exhibited dual activity against α-glucosidase (IC<sub>50</sub> = 1.08 ± 0.02 μM and 1.01 ± 0.05 μM, respectively) and α-amylase (IC<sub>50</sub> = 5.33 ± 0.01 μM and 1.18 ± 0.06 μM, respectively) compared to acarbose (IC<sub>50</sub> = 4.40 ± 0.05 μM and 2.92 ± 0.02 μM, respectively). The 6-iodo-2-(4-fluorophenyl)-substituted derivative <b>3f</b>, on the other hand, exhibited strong activity against α-amylase and significant inhibitory effect against α-glucosidase with IC<sub>50</sub> values of 0.64 ± 0.01 μM and 9.27 ± 0.02 μM, respectively. Compounds <b>3c</b>, <b>3l</b> and <b>3p</b> exhibited the highest activity against α-glucosidase with IC<sub>50</sub> values of 1.04 ± 0.03, 0.92 ± 0.01 and 0.78 ± 0.05 μM, respectively. Moderate cytotoxicity against the MCF-7 and A549 cell lines was observed for these compounds compared to the anticancer drugs doxorubicin (IC<sub>50</sub> = 0.25 ± 0.05 μM and 0.36 ± 0.07 μM, respectively) and gefitinib (IC<sub>50</sub> = 0.19 ± 0.04 μM and 0.25 ± 0.03 μM, respectively), and their IC<sub>50</sub> values are in the range of 10.38 ± 0.08–25.48 ± 0.08 μM and 11.39 ± 0.12–20.00 ± 0.05 μM, respectively. The test compounds generally exhibited moderate to strong antioxidant capabilities, as demonstrated via robust free radical scavenging activity assays, viz., DPPH and NO. The potential of selected derivatives to inhibit superoxide dismutase (SOD) was also investigated via enzymatic assay in vitro. Molecular docking revealed the N-O moiety as essential to facilitate electrostatic interactions of the test compounds with the protein residues in the active site of α-glucosidase and α-amylase. The presence of bromine and/or iodine atoms resulted in increased hydrophobic (alkyl and/or π-alkyl) interactions and therefore increased inhibitory effect against both enzymes. |
| first_indexed | 2024-03-09T17:04:29Z |
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| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T17:04:29Z |
| publishDate | 2023-11-01 |
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| series | Antioxidants |
| spelling | doaj.art-6d54170ef25b4047a2cab6b57148ef1f2023-11-24T14:25:51ZengMDPI AGAntioxidants2076-39212023-11-011211197110.3390/antiox12111971In Vitro α-Glucosidase and α-Amylase Inhibition, Cytotoxicity and Free Radical Scavenging Profiling of the 6-Halogeno and Mixed 6,8-Dihalogenated 2-Aryl-4-methyl-1,2-dihydroquinazoline 3-OxidesNontokozo M. Magwaza0Garland K. More1Samantha Gildenhuys2Malose J. Mphahlele3Department of Chemistry, College of Science, Engineering and Technology, University of South Africa, Private Bag X06, Florida 1710, South AfricaCollege of Agriculture and Environmental Sciences Laboratories, University of South Africa, Private Bag X06, Florida 1710, South AfricaDepartment of Life & Consumer Sciences, College of Agriculture and Environmental Sciences, University of South Africa, Private Bag X06, Florida 1710, South AfricaDepartment of Chemistry, College of Science, Engineering and Technology, University of South Africa, Private Bag X06, Florida 1710, South AfricaSeries of the 6-bromo/iodo substituted 2-aryl-4-methyl-1,2-dihydroquinazoline-3-oxides and their mixed 6,8-dihalogenated (Br/I and I/Br) derivatives were evaluated for inhibitory properties against α-glucosidase and/or α-amylase activities and for cytotoxicity against breast (MCF-7) and lung (A549) cancer cell lines. The 6-bromo-2-phenyl substituted <b>3a</b> and its corresponding 6-bromo-8-iodo-2-phenyl-substituted derivative <b>3i</b> exhibited dual activity against α-glucosidase (IC<sub>50</sub> = 1.08 ± 0.02 μM and 1.01 ± 0.05 μM, respectively) and α-amylase (IC<sub>50</sub> = 5.33 ± 0.01 μM and 1.18 ± 0.06 μM, respectively) compared to acarbose (IC<sub>50</sub> = 4.40 ± 0.05 μM and 2.92 ± 0.02 μM, respectively). The 6-iodo-2-(4-fluorophenyl)-substituted derivative <b>3f</b>, on the other hand, exhibited strong activity against α-amylase and significant inhibitory effect against α-glucosidase with IC<sub>50</sub> values of 0.64 ± 0.01 μM and 9.27 ± 0.02 μM, respectively. Compounds <b>3c</b>, <b>3l</b> and <b>3p</b> exhibited the highest activity against α-glucosidase with IC<sub>50</sub> values of 1.04 ± 0.03, 0.92 ± 0.01 and 0.78 ± 0.05 μM, respectively. Moderate cytotoxicity against the MCF-7 and A549 cell lines was observed for these compounds compared to the anticancer drugs doxorubicin (IC<sub>50</sub> = 0.25 ± 0.05 μM and 0.36 ± 0.07 μM, respectively) and gefitinib (IC<sub>50</sub> = 0.19 ± 0.04 μM and 0.25 ± 0.03 μM, respectively), and their IC<sub>50</sub> values are in the range of 10.38 ± 0.08–25.48 ± 0.08 μM and 11.39 ± 0.12–20.00 ± 0.05 μM, respectively. The test compounds generally exhibited moderate to strong antioxidant capabilities, as demonstrated via robust free radical scavenging activity assays, viz., DPPH and NO. The potential of selected derivatives to inhibit superoxide dismutase (SOD) was also investigated via enzymatic assay in vitro. Molecular docking revealed the N-O moiety as essential to facilitate electrostatic interactions of the test compounds with the protein residues in the active site of α-glucosidase and α-amylase. The presence of bromine and/or iodine atoms resulted in increased hydrophobic (alkyl and/or π-alkyl) interactions and therefore increased inhibitory effect against both enzymes.https://www.mdpi.com/2076-3921/12/11/1971halogenated 1,2-dihydroquinazoline 3-oxidesdiabetescytotoxicityantioxidant activitymolecular docking |
| spellingShingle | Nontokozo M. Magwaza Garland K. More Samantha Gildenhuys Malose J. Mphahlele In Vitro α-Glucosidase and α-Amylase Inhibition, Cytotoxicity and Free Radical Scavenging Profiling of the 6-Halogeno and Mixed 6,8-Dihalogenated 2-Aryl-4-methyl-1,2-dihydroquinazoline 3-Oxides Antioxidants halogenated 1,2-dihydroquinazoline 3-oxides diabetes cytotoxicity antioxidant activity molecular docking |
| title | In Vitro α-Glucosidase and α-Amylase Inhibition, Cytotoxicity and Free Radical Scavenging Profiling of the 6-Halogeno and Mixed 6,8-Dihalogenated 2-Aryl-4-methyl-1,2-dihydroquinazoline 3-Oxides |
| title_full | In Vitro α-Glucosidase and α-Amylase Inhibition, Cytotoxicity and Free Radical Scavenging Profiling of the 6-Halogeno and Mixed 6,8-Dihalogenated 2-Aryl-4-methyl-1,2-dihydroquinazoline 3-Oxides |
| title_fullStr | In Vitro α-Glucosidase and α-Amylase Inhibition, Cytotoxicity and Free Radical Scavenging Profiling of the 6-Halogeno and Mixed 6,8-Dihalogenated 2-Aryl-4-methyl-1,2-dihydroquinazoline 3-Oxides |
| title_full_unstemmed | In Vitro α-Glucosidase and α-Amylase Inhibition, Cytotoxicity and Free Radical Scavenging Profiling of the 6-Halogeno and Mixed 6,8-Dihalogenated 2-Aryl-4-methyl-1,2-dihydroquinazoline 3-Oxides |
| title_short | In Vitro α-Glucosidase and α-Amylase Inhibition, Cytotoxicity and Free Radical Scavenging Profiling of the 6-Halogeno and Mixed 6,8-Dihalogenated 2-Aryl-4-methyl-1,2-dihydroquinazoline 3-Oxides |
| title_sort | in vitro α glucosidase and α amylase inhibition cytotoxicity and free radical scavenging profiling of the 6 halogeno and mixed 6 8 dihalogenated 2 aryl 4 methyl 1 2 dihydroquinazoline 3 oxides |
| topic | halogenated 1,2-dihydroquinazoline 3-oxides diabetes cytotoxicity antioxidant activity molecular docking |
| url | https://www.mdpi.com/2076-3921/12/11/1971 |
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