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| تعداد شمارهها | 713 |
| تعداد مقالات | 10,270 |
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| تعداد دریافت فایل اصل مقاله | 63,839,910 |
Exploring new antifungal leads: synthesis, characterization, and computational study of a series of 4-(4-chlorophenyl) cyclohexane-1-carboxylic acid derivatives with promising CYP51-binding affinity | ||
| شیمى کاربردى روز | ||
| مقالات آماده انتشار، پذیرفته شده، انتشار آنلاین از تاریخ 20 تیر 1405 | ||
| نوع مقاله: مقاله علمی پژوهشی | ||
| شناسه دیجیتال (DOI): 10.22075/chem.2026.41619.2460 | ||
| نویسندگان | ||
| Saja Alsalhy* 1؛ Hussam w. Al-humadi2 | ||
| 1College of Pharmacy, University of Babylon | ||
| 2College of Pharmacy, University of Babylon, Hillah, Iraq | ||
| تاریخ دریافت: 26 خرداد 1405، تاریخ بازنگری: 17 تیر 1405، تاریخ پذیرش: 20 تیر 1405 | ||
| چکیده | ||
| ABSTRACT: Starting from 4-(4-chlorophenyl) cyclohexane-1-carboxylic acid, a multi-steps processes were used to create a novel series of 1,2,4-triazole derivatives with a 4-(4-chlorophenyl) cyclohexane moiety. These processes included Fischer esterification, hydrazide formation, thiosemicarbazides preparation, cyclization to form the triazole core (Compound 5), and subsequent S-alkylation with butyl iodide, iodoethane, and ethyl bromo acetate to produce derivatives 5a, 5b, and 5c. FT-IR and 1H NMR spectroscopy were used to describe each constituent. All derivatives successfully bonded inside the active site of the fungal CYP51 enzyme (PDB: 4WMZ), according to molecular docking, with significant pi-alkyl and pi-sulphur interactions with important residues like Lys151, Tyr140, His468, and Cys470. Compound 5 had the highest binding affinity (-10.1 kcal/mol), which was comparable to the reference medication fluconazole (-11.9 kcal/mol). All compounds met Lipinski's rule of five, had favourable physicochemical characteristics with a high bioavailability score of 0.55, and were not anticipated to cross the blood-brain barrier, according to ADMET profiling using Swiss ADME. Notably, Compound 5 was uniquely predicted to have high gastrointestinal absorption despite the majority of derivatives being P-glycoprotein substrates with low absorption. These results suggest that Compound 5 is a viable lead candidate for additional in vitro and in vivo testing as a possible antifungal drug. | ||
| کلیدواژهها | ||
| Heterocyclic compounds؛ 1؛ 2؛ 4-Triazole؛ ADMET profiling؛ Molecular docking؛ Fungal infections | ||
| عنوان مقاله [English] | ||
| Exploring new antifungal leads: synthesis, characterization, and computational study of a series of 4-(4-chlorophenyl) cyclohexane-1-carboxylic acid derivatives with promising CYP51-binding affinity | ||
| نویسندگان [English] | ||
| Saja Alsalhy1؛ Hussam w. Al-humadi2 | ||
| 1College of Pharmacy, University of Babylon | ||
| 2College of Pharmacy, University of Babylon, Hillah, Iraq | ||
| چکیده [English] | ||
| ABSTRACT: Starting from 4-(4-chlorophenyl) cyclohexane-1-carboxylic acid, a multi-steps processes were used to create a novel series of 1,2,4-triazole derivatives with a 4-(4-chlorophenyl) cyclohexane moiety. These processes included Fischer esterification, hydrazide formation, thiosemicarbazides preparation, cyclization to form the triazole core (Compound 5), and subsequent S-alkylation with butyl iodide, iodoethane, and ethyl bromo acetate to produce derivatives 5a, 5b, and 5c. FT-IR and 1H NMR spectroscopy were used to describe each constituent. All derivatives successfully bonded inside the active site of the fungal CYP51 enzyme (PDB: 4WMZ), according to molecular docking, with significant pi-alkyl and pi-sulphur interactions with important residues like Lys151, Tyr140, His468, and Cys470. Compound 5 had the highest binding affinity (-10.1 kcal/mol), which was comparable to the reference medication fluconazole (-11.9 kcal/mol). All compounds met Lipinski's rule of five, had favourable physicochemical characteristics with a high bioavailability score of 0.55, and were not anticipated to cross the blood-brain barrier, according to ADMET profiling using Swiss ADME. Notably, Compound 5 was uniquely predicted to have high gastrointestinal absorption despite the majority of derivatives being P-glycoprotein substrates with low absorption. These results suggest that Compound 5 is a viable lead candidate for additional in vitro and in vivo testing as a possible antifungal drug. | ||
| کلیدواژهها [English] | ||
| Heterocyclic compounds, 1, 2, 4-Triazole, ADMET profiling, Molecular docking, Fungal infections | ||
| مراجع | ||
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آمار تعداد مشاهده مقاله: 6 |
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