Design, synthesis, α-glucosidase inhibition, pharmacokinetic, and cytotoxic studies of new indole-carbohydrazide-phenoxy-N-phenylacetamide derivatives.

Autor: Hamedifar H; CinnaGen Medical Biotechnology Research Center, Alborz University of Medical Sciences, Karaj, Iran.; CinnaGen Research and Production Co., Alborz, Iran., Mohammadi-Khanaposhtani M; Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran., Sherafati M; Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran., Noori M; Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran., Moazam A; Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran., Hosseini S; Shahid Beheshti University of Medical Sciences, Tehran, Iran., Larijani B; Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran., Hajimiri MH; CinnaGen Medical Biotechnology Research Center, Alborz University of Medical Sciences, Karaj, Iran.; CinnaGen Research and Production Co., Alborz, Iran., Mahdavi M; Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran., Erdogan MK; Department of Molecular Biology and Genetics, Faculty of Arts and Sciences, Bingol University, Bingol, Turkiye., Gundogdu R; Department of Molecular Biology and Genetics, Faculty of Arts and Sciences, Bingol University, Bingol, Turkiye., Kirici M; Department of Molecular Biology and Genetics, Faculty of Arts and Sciences, Bingol University, Bingol, Turkiye., Taslimi P; Department of Biotechnology, Faculty of Science, Bartin University, Bartin, Turkiye., Gülçin İ; Department of Chemistry, Faculty of Science, Ataturk University, Erzurum, Turkiye.
Jazyk: angličtina
Zdroj: Archiv der Pharmazie [Arch Pharm (Weinheim)] 2023 Jun; Vol. 356 (6), pp. e2200571. Date of Electronic Publication: 2023 Apr 05.
DOI: 10.1002/ardp.202200571
Abstrakt: A new series of indole-carbohydrazide-phenoxy-N-phenylacetamide derivatives 7a-l were designed, synthesized, and screened for their α-glucosidase inhibitory abilities and cytotoxic effects. The results obtained in the α-glucosidase inhibition assay indicated that most of the synthesized derivatives displayed good to moderate inhibitory abilities (K i values ranging from 14.65 ± 2.54 to 37.466 ± 6.46 μM) when compared with the standard drug acarbose (K i  = 42.38 ± 5.73 μM). Among them, 2-mehoxy-phenoxy derivatives 7l and 7h with 4-nitro and 4-chloro substituents on the phenyl ring of the N-phenylacetamide moiety, respectively, displayed the most inhibition effects. The inhibitory mechanism of these compounds was investigated by molecular docking studies. The in vitro cytotoxicity assay showed that only one compound, 2-methoxy-phenoxy derivative 7k with a 4-bromo substituent on the phenyl ring of the N-phenylacetamide moiety, exhibited moderate cytotoxicity against the human non-small-cell lung cancer cell line A549 and the rest of the compounds show almost no cytotoxicity. Further cytotoxic evaluations were also performed on compound 7k. The in silico pharmacokinetic study predicted that the selected compounds 7l and 7h are likely to be orally active.
(© 2023 Deutsche Pharmazeutische Gesellschaft.)
Databáze: MEDLINE
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