دورية أكاديمية
Redefining a new frontier in alkaptonuria therapy with AI-driven drug candidate design via in- silico innovation.
| العنوان: | Redefining a new frontier in alkaptonuria therapy with AI-driven drug candidate design via in- silico innovation. |
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| المؤلفون: | Naveed M; Department of Biotechnology, Faculty of Science and Technology, University of Central Punjab, Lahore, 54590, Pakistan., Javed K; Department of Biotechnology, Faculty of Science and Technology, University of Central Punjab, Lahore, 54590, Pakistan., Aziz T; Laboratory of Animal Health Food Hygiene, Quality University of Ioannina, Arta 47132, Greece., Zafar A; Department of Biotechnology, Faculty of Science and Technology, University of Central Punjab, Lahore, 54590, Pakistan., Fatima M; Department of Biotechnology, Faculty of Science and Technology, University of Central Punjab, Lahore, 54590, Pakistan., Ali I; Department of Biotechnology, Faculty of Science and Technology, University of Central Punjab, Lahore, 54590, Pakistan., Khan AA; Department of Biotechnology University of Malakand, Chakdara 18800, Pakistan., Albekairi TH; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. |
| المصدر: | Zeitschrift fur Naturforschung. C, Journal of biosciences [Z Naturforsch C J Biosci] 2024 Jul 12. Date of Electronic Publication: 2024 Jul 12. |
| Publication Model: | Ahead of Print |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: De Gruyter Country of Publication: Germany NLM ID: 8912155 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1865-7125 (Electronic) Linking ISSN: 03410382 NLM ISO Abbreviation: Z Naturforsch C J Biosci Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Berlin : De Gruyter Original Publication: Tübingen : Verlag der Zeitschrift für Naturforschung, 1986- |
| مستخلص: | A rare metabolic condition called alkaptonuria (AKU) is caused by a decrease in homogentisate 1,2 dioxygenase (HGO) activity due to a mutation in homogentisate dioxygenase (HGD) gene. Homogentisic acid is a byproduct of the catabolism of tyrosine and phenylalanine that darkens the urine and accumulates in connective tissues which causes an agonizing arthritis. Employing the use of deep learning artificial intelligence (AI) drug design, this study aims to alleviate the current toxicity of the AKU drugs currently in use, particularly nitisinone, by utilizing the natural flavanol kaempferol molecule as a 4-hydroxyphenylpyruvate dioxygenase inhibitor. Kaempferol was employed to generate three effective de novo drug candidates targeting the enzyme 4-hydroxyphenylpyruvate dioxygenase using an AI drug design tool. We present novel AIK formulations in the present study. The AIK's (Artificial Intelligence Kaempferol) examination of drug-likeliness among the three led to its choice as a possible target. The toxicity assessment research of AIK demonstrates that it is not only safer to use than other treatments, but also more efficient. The docking of the AIGT with 4-hydroxyphenylpyruvate dioxygenase, which revealed a binding affinity of around -9.099 kcal/mol, highlights the AIK's potential as a therapeutic candidate. An innovative approach to deal with challenging circumstances is thus presented in this study by new formulations kaempferol that have been meticulously designed by AI. The results of the in vitro tests must be confirmed in vivo , even though AI-designed AIK is effective and sufficiently safe as computed. (© 2024 the author(s), published by De Gruyter, Berlin/Boston.) |
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| فهرسة مساهمة: | Keywords: AI; alkaptonuria; de novo drug candidate; kaempferol; nitisinone; toxicity |
| تواريخ الأحداث: | Date Created: 20240712 Latest Revision: 20240712 |
| رمز التحديث: | 20240713 |
| DOI: | 10.1515/znc-2024-0075 |
| PMID: | 38996180 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1865-7125 |
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| DOI: | 10.1515/znc-2024-0075 |