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Computational and in vitro screening validates the repositioning potential of Coxibs as anti-fibrotic agents.

التفاصيل البيبلوغرافية
العنوان: Computational and in vitro screening validates the repositioning potential of Coxibs as anti-fibrotic agents.
المؤلفون: Karande S; Department of Biotechnology, DPSRU, New Delhi, India., Das B; KIIT School of Biotechnology, KIIT Deemed to be University, Bhubaneswar, India., Acharya SS; KIIT School of Biotechnology, KIIT Deemed to be University, Bhubaneswar, India., Kumar A; Department of Pharmacology, DPSRU, New Delhi, India., Patel H; Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, India., Sharma A; Department of Pharmacognosy, DPSRU, New Delhi, India., Gupta M; Department of Pharmaceutics, DPSRU, New Delhi, India., Ahmad I; Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, India., Bhandare V; ICMR-National Institute of Traditional Medicine, Belagavi, India., Sharma K; Department of Pharmaceutical Chemistry, DPSRU, New Delhi, India., Kundu CN; KIIT School of Biotechnology, KIIT Deemed to be University, Bhubaneswar, India., Patil C; Department of Pharmacology, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, India.
المصدر: Journal of biomolecular structure & dynamics [J Biomol Struct Dyn] 2024 Mar 03, pp. 1-13. Date of Electronic Publication: 2024 Mar 03.
Publication Model: Ahead of Print
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Taylor & Francis Country of Publication: England NLM ID: 8404176 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1538-0254 (Electronic) Linking ISSN: 07391102 NLM ISO Abbreviation: J Biomol Struct Dyn Subsets: MEDLINE
أسماء مطبوعة: Publication: June 2012- : Oxon, UK : Taylor & Francis
Original Publication: Guilderland, NY : Adenine Press, [c1983-
مستخلص: Idiopathic pulmonary fibrosis (IPF) is a life-threatening disease with a survival rate of <5 years. The TGF-β plays a significant role in the progression and severity of IPF. The TGF-β receptor type1 TGFBR1 antagonists inhibit the process of fibrosis and may have a role in the treatment of IPF. The main objective of the study was to identify promising drug candidates against IPF using In-silico and In-vitro evaluation methods. An in-silico screening was carried out of the marketed Coxibs to find their TGFBR1 inhibitory potential considering their structural resemblance with the JZO-a co-crystalized ligand of the crystal structure of the TGFBR1. The virtual screening yielded rofecoxib as a TGFBR1 ligand with a significant docking score. To further validate the outcome of molecular docking studies, MD simulation of 200 ns was carried out followed by the determination of conformational stability, binding free energy calculation using MMPBSA/MMGBSA, and Free Energy Landscape (FEL). The therapeutic efficacy of rofecoxib was compared with that of nintedanib (a therapeutic agent used in the treatment of IPF) at equimolar concentrations (5 µM). The model of TGF-β1 (1 ng/ml)-induced EMT of A549 was used to determine the effect of rofecoxib on the EMT markers like cellular morphology, cytokine expressions, fibrosis associated protein, E-cadherin, and α-smooth muscle actin. In vitro results indicated that rofecoxib significantly suppresses the TGF-β1-induced EMT of A549 cells and validates the possible preventive/protective role of rofecoxib in pulmonary fibrosis. In conclusion, rofecoxib may be considered for repositioning as an anti-fibrotic agent.Communicated by Ramaswamy H. Sarma.
فهرسة مساهمة: Keywords: COX-2 inhibitor; Idiopathic pulmonary fibrosis; TGF-β1; TGFBR1; epithelial-mesenchymal transition
تواريخ الأحداث: Date Created: 20240304 Latest Revision: 20240304
رمز التحديث: 20240304
DOI: 10.1080/07391102.2024.2318655
PMID: 38433403
قاعدة البيانات: MEDLINE
الوصف
تدمد:1538-0254
DOI:10.1080/07391102.2024.2318655