Synthesis of novel Bis-1,2,4-Triazolo[3,4-b][1,3,4]Thiadiazines from natural camphoric acid as potential anti-candidal agents
Candida species have long been attributed to various diseases like candidiasis and systemic diseases and exacerbate the symptoms of immunocompromised patients. Candida species have enzymes that could function as drug targets to decrease their pathogenicity and eradicate the fungi. This research aime...
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Elsevier
2024-01-01
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| Series: | Results in Chemistry |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211715624001024 |
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| author | Salama A. Ouf Sobhi M. Gomha Basant Farag Magdi E.A. Zaki Mohamed M. Ewies Ihab A.A. Sharawy Fatma O. Khalil Huda K. Mahmoud |
| author_facet | Salama A. Ouf Sobhi M. Gomha Basant Farag Magdi E.A. Zaki Mohamed M. Ewies Ihab A.A. Sharawy Fatma O. Khalil Huda K. Mahmoud |
| author_sort | Salama A. Ouf |
| collection | DOAJ |
| description | Candida species have long been attributed to various diseases like candidiasis and systemic diseases and exacerbate the symptoms of immunocompromised patients. Candida species have enzymes that could function as drug targets to decrease their pathogenicity and eradicate the fungi. This research aimed to investigate the potency of new bis-triazolothiadiazine derivatives contained in inhibiting important enzymes of C. albicans as an example, through molecular docking simulation. Thus, a novel series of bis-triazolo[3,4-b][1,3,4]thiadiazines were designed and prepared via the reaction of the most versatile, hitherto unreported 5,5′-(1,2,2-trimethylcyclopentane-1,3-diyl)bis(4-amino-2,4-dihydro-3H-1,2,4-triazole-3-thione) with the appropriate hydrazonoyl halides and phenacyl bromides. Various spectroscopic techniques were used to identify the structures of the synthesized derivatives. The synthesized derivatives were tested against different species of Candida spp. The most effective compound was 6f followed by 6b, 6d, and 6e, where the inhibition zone ranged from 45 mm to 38 mm. By using molecular docking, which highlighted the important interactions with the amino acid residues Lys57, Leu77, Glu116, Gly114, Phe36, Thr58, and Glu32 at the point of binding, it was possible to determine the binding interactions of the produced derivatives to the fluconazole target fungi. The binding interaction energy was discovered to be −6.494 kcal/mol for the fungi candida albicans (PDB ID: 1IA2). The derivatives 6f and 6d, which demonstrated the highest efficacy, displayed significant conserved interactions with the amino acid residues at the binding site of the fluconazole fungi, in conjunction with the PDB co-crystal ligand 1IA2. The study’s results also revealed that the dG scores of the novel bis-triazolo-thiadiazines 6b-f. The study shows good docking scores with acceptable binding interactions. Finally, molecular docking studies revealed the lowest binding activity of derivatives 6e and 6c with the target fungi. |
| first_indexed | 2024-03-07T14:01:32Z |
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| institution | Directory Open Access Journal |
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| last_indexed | 2024-03-07T14:01:32Z |
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| spelling | doaj.art-e1b17bbf55c246e3bc2668e6c5c92df22024-03-07T05:27:39ZengElsevierResults in Chemistry2211-71562024-01-017101406Synthesis of novel Bis-1,2,4-Triazolo[3,4-b][1,3,4]Thiadiazines from natural camphoric acid as potential anti-candidal agentsSalama A. Ouf0Sobhi M. Gomha1Basant Farag2Magdi E.A. Zaki3Mohamed M. Ewies4Ihab A.A. Sharawy5Fatma O. Khalil6Huda K. Mahmoud7Botany & Microbiology Department, Faculty of Science, Cairo University, Giza 12613, EgyptDepartment of Chemistry, Faculty of Science, Islamic University of Madinah, Madinah 42351, Saudi Arabia; Corresponding author.Department of Chemistry, Faculty of Science, Zagazig University, Zagazig 44519, EgyptDepartment of Chemistry, Faculty of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11623, Saudi ArabiaBotany & Microbiology Department, Faculty of Science, Cairo University, Giza 12613, EgyptBotany & Microbiology Department, Faculty of Science, Cairo University, Giza 12613, EgyptDepartment of Clinical Microbiology and Immunology, National Liver Institute, Menoufia University, Cairo, EgyptChemistry Department, Faculty of Science, Cairo University, Giza 12613, EgyptCandida species have long been attributed to various diseases like candidiasis and systemic diseases and exacerbate the symptoms of immunocompromised patients. Candida species have enzymes that could function as drug targets to decrease their pathogenicity and eradicate the fungi. This research aimed to investigate the potency of new bis-triazolothiadiazine derivatives contained in inhibiting important enzymes of C. albicans as an example, through molecular docking simulation. Thus, a novel series of bis-triazolo[3,4-b][1,3,4]thiadiazines were designed and prepared via the reaction of the most versatile, hitherto unreported 5,5′-(1,2,2-trimethylcyclopentane-1,3-diyl)bis(4-amino-2,4-dihydro-3H-1,2,4-triazole-3-thione) with the appropriate hydrazonoyl halides and phenacyl bromides. Various spectroscopic techniques were used to identify the structures of the synthesized derivatives. The synthesized derivatives were tested against different species of Candida spp. The most effective compound was 6f followed by 6b, 6d, and 6e, where the inhibition zone ranged from 45 mm to 38 mm. By using molecular docking, which highlighted the important interactions with the amino acid residues Lys57, Leu77, Glu116, Gly114, Phe36, Thr58, and Glu32 at the point of binding, it was possible to determine the binding interactions of the produced derivatives to the fluconazole target fungi. The binding interaction energy was discovered to be −6.494 kcal/mol for the fungi candida albicans (PDB ID: 1IA2). The derivatives 6f and 6d, which demonstrated the highest efficacy, displayed significant conserved interactions with the amino acid residues at the binding site of the fluconazole fungi, in conjunction with the PDB co-crystal ligand 1IA2. The study’s results also revealed that the dG scores of the novel bis-triazolo-thiadiazines 6b-f. The study shows good docking scores with acceptable binding interactions. Finally, molecular docking studies revealed the lowest binding activity of derivatives 6e and 6c with the target fungi.http://www.sciencedirect.com/science/article/pii/S2211715624001024Camphoric acid1,2,4-triazolesTriazolo-thiadiazinesHydrazonoyl halidesMolecular dockingAntifungal evaluation |
| spellingShingle | Salama A. Ouf Sobhi M. Gomha Basant Farag Magdi E.A. Zaki Mohamed M. Ewies Ihab A.A. Sharawy Fatma O. Khalil Huda K. Mahmoud Synthesis of novel Bis-1,2,4-Triazolo[3,4-b][1,3,4]Thiadiazines from natural camphoric acid as potential anti-candidal agents Results in Chemistry Camphoric acid 1,2,4-triazoles Triazolo-thiadiazines Hydrazonoyl halides Molecular docking Antifungal evaluation |
| title | Synthesis of novel Bis-1,2,4-Triazolo[3,4-b][1,3,4]Thiadiazines from natural camphoric acid as potential anti-candidal agents |
| title_full | Synthesis of novel Bis-1,2,4-Triazolo[3,4-b][1,3,4]Thiadiazines from natural camphoric acid as potential anti-candidal agents |
| title_fullStr | Synthesis of novel Bis-1,2,4-Triazolo[3,4-b][1,3,4]Thiadiazines from natural camphoric acid as potential anti-candidal agents |
| title_full_unstemmed | Synthesis of novel Bis-1,2,4-Triazolo[3,4-b][1,3,4]Thiadiazines from natural camphoric acid as potential anti-candidal agents |
| title_short | Synthesis of novel Bis-1,2,4-Triazolo[3,4-b][1,3,4]Thiadiazines from natural camphoric acid as potential anti-candidal agents |
| title_sort | synthesis of novel bis 1 2 4 triazolo 3 4 b 1 3 4 thiadiazines from natural camphoric acid as potential anti candidal agents |
| topic | Camphoric acid 1,2,4-triazoles Triazolo-thiadiazines Hydrazonoyl halides Molecular docking Antifungal evaluation |
| url | http://www.sciencedirect.com/science/article/pii/S2211715624001024 |
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