QSAR Studies of some New Synthesized Diacylhydrazine Compounds Derived from Indomethacin as Caspase-1 Inhibitors

H. Al-Naimi, Kawther; A. A-Alwahb, Haitham; Y. Hussien, Hyffaa

doi:10.33899/rjs.2018.141185

	QSAR Studies of some New Synthesized Diacylhydrazine Compounds Derived from Indomethacin as Caspase-1 Inhibitors
Rafidain Journal of Science
Article 6, Volume 27, Issue 1, 2018, Pages 43-51 PDF (0 K)
DOI: 10.33899/rjs.2018.141185
Authors
Kawther H. Al-Naimi; Haitham A. A-Alwahb; Hyffaa Y. Hussien
Abstract
Indomethacin (1) reacts with absolute ethanol in presence of conc. sulphuric acid to form the ester (2). This ester was converted into the hydrazide (3) by treatment with hydrazine hydrate. The reaction of the hydrazide (3) with acid chlorides (of indomethacine, dichlofenac, mefenamic acid, aspirin and ibuprofen) in dry xylene afforded the N,N’-diacylhydrazine compounds (4-8). A series of new 2,5-disubstituted-1,3,4-oxadiazoles (9-13) derived from indomethacin (1) was obtained by the dehydrative cyclization of the corresponding N,N’-diacylhydrazines(4-8), in presence of an excess of thionyl chloride. The quantitative structure-activity relationship (QSAR) analysis of the synthesized compounds was also performed to compute the parameters that affect the biological activity (inhibitory activity IC50). Docking analysis was also performed to predict the interactions between the synthesized compounds with Caspase-1 (Interleukin-1 converting enzyme). The study is aimed to predict factor affecting the biological activity of the prepared compounds by employing the QSAR analysis. The structures of the synthesized compounds were confirmed by the spectroscopic methods
Keywords
Indomethacin; diacylhydrazine; Disubstituted; Oxadiazoles; QSAR and docking; QSAR

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