Synthesis, anticancer evaluation and docking studies of novel adamantanyl-1,3,4-oxadiazol hybrid compounds as Aurora-A kinase inhibitors

Abstract

Cancer is a devastating disease, but advancements in cancer treatment offer hope for the future. Aurora Kinases are a family of serine/threonine kinases that play critical roles in cell cycle control and mitosis. There are three members of the Aurora kinase family in humans: Aurora-A kinase, Aurora-B kinase, and Aurora-C kinase. This study focuses on the synthesis of hybrid compounds combining adamantane and 1,3,4-oxadiazole as potential inhibitors of Aurora-A kinase. A series of novel 4- ((5-((3r,5r,7r)-adamantan-1yl)-1,3,4-oxadiazol-2-yl)thio)-N,N-2-yn-1-amine were synthesized and evaluated against Aurora-A kinase.The most potent derivatives were 6a and 6k with IC 50 values 36.6 and 38.8 μM, respectively. Docking studies probed the binding interactions of these compounds within the active site of the kinase. The ndings contribute to the development of novel cancer therapeutics and offer promise for more effective and targeted treatments in the future.

Synthesis, evaluation, and docking study of adamantyl-1,3,4-oxadiazol hybrid compounds as CaMKIIδ kinase inhibitor

“…High-resolution mass spectrometry (HRMS), 1 H, 13 C NMR, and IR spectroscopy were used to characterize the synthesize compounds (spectra of all compounds HRMS, IR, 1 H and 13 C NMR, are available in SI file). The mass spectra were found to be in highly agreement with estimated values and provided the right molecular ion peaks.…”

“…Resonances were observed for all aromatic rings at δ = 6.70-8.22 ppm. However, all of the produced compounds' distinctive signals were seen in the 13 C NMR spectra, which also included several aliphatic peaks for the aliphatic amine (region δ = 12.0-39.5 ppm) and adamantly (region δ = 41.0-58.0 ppm) moieties. In the aromatic area (region δ = 103.0-152.0 ppm), every aromatic moiety displayed accurate and distinct carbon signals.…”

“…Using TMS as an internal standard, 1 H NMR spectra were captured using a Bruker Avance III-500 MHz spectrometer. 13 C NMR spectra were collected at 125 MHz on the same equipment. Chemical shifts were expressed as ppm-values for δ-.…”

“…4,5,[10][11][12] As part of our ongoing interest in the discovery and design of adamantyl-1,3,4-oxadiazole hybrids as bioactive compounds. [13][14][15][16][17] As potential CaMKIIδ kinase inhibitors, we had an interest in creating hybrid adducts of adamantane/1,3,4-oxadiazole. The synthesis of target compounds pharmacophore was obtained using a Cu-catalyzed Mannich reaction 13,14,18,19 (Scheme 1).…”

“…[13][14][15][16][17] As potential CaMKIIδ kinase inhibitors, we had an interest in creating hybrid adducts of adamantane/1,3,4-oxadiazole. The synthesis of target compounds pharmacophore was obtained using a Cu-catalyzed Mannich reaction 13,14,18,19 (Scheme 1).…”