Investigation of corticosteroid-NSAID prodrugs for TNF-α and IL6 receptors, their characterization, single crystal XRD and DFT studies: A combined experimental and theoretical approach

• Published in: Journal of molecular structure Vol. 1296; p. 136851
• Main Authors: Yadav, Astha, Singh, Asmita, Rawat, Poonam, Pal, Anirban, Yadav, Priyanka, Tyagi, Vidushi, Singh, Saurabh Kumar, Sethi, Arun, Singh, Ranvijay Pratap
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 15-01-2024
• Subjects: Corticosteroids; IL-6; Pro-inflammatory cytokines; Single crystal-XRD; TNF-α; Pro-inflammatory cytokines; Single crystal-XRD; Corticosteroids; TNF-α; IL-6
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2023.136851

•Novel corticosteroids derivatives have been synthesized.•Compounds characterized by FT-IR, 1H NMR, 13C NMR, UV–Vis, ESI-MS and single crystal XRD.•Compounds have been identified as potential TNF alpha and IL6 inhibitors.•DFT studies supported the experimental values interpreted in the spectra.•NLO study reveals that synthesized compounds are attractive material for non-linear optical applications.
In continuation of our research towards the synthesis of steroidal derivatives, we have synthesized corticosteroids-NSAIDs derivatives 3i-3p as potent anti-inflammatory agents. The products obtained have been characterized using elemental analysis, spectroscopic techniques (FT-IR, 1H NMR, 13C NMR, UV–Vis and mass spectrometry) and product 3k has also been characterized with the help of single crystal X-ray crystallography. The inhibition of pro-inflammatory cytokines is a key approach to abate severe inflammation. In this work a series of corticosteroids-NSAIDs derivatives are reported whose activity were performed on RAW264.7 cell line and have been identified as potential TNF alpha and IL6 inhibitors. Our work demonstrates that these corticosteroid derivatives may be useful for the development of anti-inflammatory agents. Among these derivatives, 11,17-dihydroxy-3,20-diketo-pregn-1,4-diene-21-yl-2-(1,8‑diethyl-1,3,4,9-tetrahydropyrano[3,4-β]indol-1-yl)acetate (3j) was identified as the most potent anti-inflammatory agent, which showed significant anti-inflammatory activity by inhibiting the LPS-induced pro-inflammatory mediator TNF-α and IL6 in a dose-dependent manner without any cytotoxicity.
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