Anticancer, antimicrobial and molecular docking analysis of newly synthesized iodoquinazoline derivatives
Abstract The 4-anilinoquinazoline sulfonamide derivatives in medicinal chemistry are well-known antitumor backbones via different mechanisms. Herein, we reported the synthesis of five new 2,4-disubstituted-6-iodoquinazoline derivatives coded compounds 3a–e. The respective compounds were examined for...
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SpringerOpen
2025-06-01
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| Series: | AMB Express |
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| Online Access: | https://doi.org/10.1186/s13568-025-01899-1 |
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| author | Khaled M. Aboshanab Amr S. Bishr Siti Azma Jusoh Mohammad Y. Alshahrani Khondaker Miraz Rahman Ahmed M. Alafeefy |
| author_facet | Khaled M. Aboshanab Amr S. Bishr Siti Azma Jusoh Mohammad Y. Alshahrani Khondaker Miraz Rahman Ahmed M. Alafeefy |
| author_sort | Khaled M. Aboshanab |
| collection | DOAJ |
| description | Abstract The 4-anilinoquinazoline sulfonamide derivatives in medicinal chemistry are well-known antitumor backbones via different mechanisms. Herein, we reported the synthesis of five new 2,4-disubstituted-6-iodoquinazoline derivatives coded compounds 3a–e. The respective compounds were examined for their antiproliferative, antimicrobial, and carbonic anhydrase XII (CAXII) inhibitory activity against four cancerous cell lines. Compound 3c was proven to be the most effective as an anticancer. It stopped the growth of the four used tumor cell lines at concentrations ranging from 4.0 to 8.0 µM as compared to the reference doxorubicin (2.3–3.25 µM). Compound 3b, was able to stop the proliferation of the tumor cell lines with IC50 between 6.0 and 9.0 µM. The five compounds exhibited both broad-spectrum and antifungal action; however, their antibacterial activities against Gram-positive bacteria were superior to those of Gram-negative. Compound 3c showed the strongest antibacterial and antifungal activities, followed by compound 3b. In conclusion, the 4-substituted-anilino derivatives equipped with sulfonamide at position 4 of the quinazoline nucleus are suitable antitumor lead compounds. Moreover, the 4-methoxyphenyl substituent at position-2 has a better impact on activity than unsubstituted or even other substituents. The lab results are aligned with molecular docking analysis of the respective compounds against the potential targets, including CAXII, human thymidylate synthase (hTS), and human thymidine kinase (hTK), for the anticancer activities and DHFR of E. coli and S. aureus for the antibacterial properties. Compounds 3c and 3b are highly recommended for preclinical and clinical evaluation as anticancer and/or antibacterial agents for potential use in humans. |
| format | Article |
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| institution | OA Journals |
| issn | 2191-0855 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | AMB Express |
| spelling | doaj-art-9a78db2c5f7041f7beb2c7f149dd6d642025-08-20T02:10:31ZengSpringerOpenAMB Express2191-08552025-06-0115111510.1186/s13568-025-01899-1Anticancer, antimicrobial and molecular docking analysis of newly synthesized iodoquinazoline derivativesKhaled M. Aboshanab0Amr S. Bishr1Siti Azma Jusoh2Mohammad Y. Alshahrani3Khondaker Miraz Rahman4Ahmed M. Alafeefy5Department of Microbiology and Immunology, Faculty of Pharmacy, Ain Shams UniversityDepartment of Microbiology and Immunology, Faculty of Pharmacy, Ain Shams UniversityDepartment of Pharmacology and Life Sciences, Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Puncak Alam CampusCentral Labs, King Khalid UniversitySchool of Cancer and Pharmaceutical Science, King’s College LondonDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Puncak Alam CampusAbstract The 4-anilinoquinazoline sulfonamide derivatives in medicinal chemistry are well-known antitumor backbones via different mechanisms. Herein, we reported the synthesis of five new 2,4-disubstituted-6-iodoquinazoline derivatives coded compounds 3a–e. The respective compounds were examined for their antiproliferative, antimicrobial, and carbonic anhydrase XII (CAXII) inhibitory activity against four cancerous cell lines. Compound 3c was proven to be the most effective as an anticancer. It stopped the growth of the four used tumor cell lines at concentrations ranging from 4.0 to 8.0 µM as compared to the reference doxorubicin (2.3–3.25 µM). Compound 3b, was able to stop the proliferation of the tumor cell lines with IC50 between 6.0 and 9.0 µM. The five compounds exhibited both broad-spectrum and antifungal action; however, their antibacterial activities against Gram-positive bacteria were superior to those of Gram-negative. Compound 3c showed the strongest antibacterial and antifungal activities, followed by compound 3b. In conclusion, the 4-substituted-anilino derivatives equipped with sulfonamide at position 4 of the quinazoline nucleus are suitable antitumor lead compounds. Moreover, the 4-methoxyphenyl substituent at position-2 has a better impact on activity than unsubstituted or even other substituents. The lab results are aligned with molecular docking analysis of the respective compounds against the potential targets, including CAXII, human thymidylate synthase (hTS), and human thymidine kinase (hTK), for the anticancer activities and DHFR of E. coli and S. aureus for the antibacterial properties. Compounds 3c and 3b are highly recommended for preclinical and clinical evaluation as anticancer and/or antibacterial agents for potential use in humans.https://doi.org/10.1186/s13568-025-01899-1QuinazolineSulfonamideCarbonic anhydraseCancerAntimicrobialMolecular docking |
| spellingShingle | Khaled M. Aboshanab Amr S. Bishr Siti Azma Jusoh Mohammad Y. Alshahrani Khondaker Miraz Rahman Ahmed M. Alafeefy Anticancer, antimicrobial and molecular docking analysis of newly synthesized iodoquinazoline derivatives AMB Express Quinazoline Sulfonamide Carbonic anhydrase Cancer Antimicrobial Molecular docking |
| title | Anticancer, antimicrobial and molecular docking analysis of newly synthesized iodoquinazoline derivatives |
| title_full | Anticancer, antimicrobial and molecular docking analysis of newly synthesized iodoquinazoline derivatives |
| title_fullStr | Anticancer, antimicrobial and molecular docking analysis of newly synthesized iodoquinazoline derivatives |
| title_full_unstemmed | Anticancer, antimicrobial and molecular docking analysis of newly synthesized iodoquinazoline derivatives |
| title_short | Anticancer, antimicrobial and molecular docking analysis of newly synthesized iodoquinazoline derivatives |
| title_sort | anticancer antimicrobial and molecular docking analysis of newly synthesized iodoquinazoline derivatives |
| topic | Quinazoline Sulfonamide Carbonic anhydrase Cancer Antimicrobial Molecular docking |
| url | https://doi.org/10.1186/s13568-025-01899-1 |
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