Synthesis, anticancer evaluation and docking studies of novel adamantanyl-1,3,4-oxadiazol hybrid compounds as Aurora-A kinase inhibitors
Areej M. Jaber,
Mohammed M. Al-Mahadeen,
Raed A. Al-Qawasmeh
et al.
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)-adama… Show more
“…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.…”
Section: Chemistrymentioning
confidence: 99%
“…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.…”
Section: Chemistrymentioning
confidence: 99%
“…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-.…”
Section: Chemicals and Instrumentsmentioning
confidence: 99%
“…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).…”
Section: Introductionmentioning
confidence: 99%
“…[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).…”
This study revealed a new inhibitor of Ca2+/calmodulin-dependent protein kinase II (CaMKII), a crucial factor in cardiovascular disease and hypertension. The study focuses on the bioactivity compounds that combine adamantane/1,3,4-oxadiazole, potentially inhibiting CaMKIIδ. Various adamantyl-1,3,4-oxadiazole derivatives were synthesized and tested for their efficiency against CaMKIIδ kinase, with 6f being the most potent with an IC50 value of 14.4 μM. Docking studies were carried out to determine the binding processes of these chemicals within the kinase’s active region. These discoveries are an important step toward the development of novel treatments for cardiovascular illnesses and hypertension, with the potential for more precise and efficient therapeutic interventions in the future.
“…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.…”
Section: Chemistrymentioning
confidence: 99%
“…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.…”
Section: Chemistrymentioning
confidence: 99%
“…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-.…”
Section: Chemicals and Instrumentsmentioning
confidence: 99%
“…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).…”
Section: Introductionmentioning
confidence: 99%
“…[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).…”
This study revealed a new inhibitor of Ca2+/calmodulin-dependent protein kinase II (CaMKII), a crucial factor in cardiovascular disease and hypertension. The study focuses on the bioactivity compounds that combine adamantane/1,3,4-oxadiazole, potentially inhibiting CaMKIIδ. Various adamantyl-1,3,4-oxadiazole derivatives were synthesized and tested for their efficiency against CaMKIIδ kinase, with 6f being the most potent with an IC50 value of 14.4 μM. Docking studies were carried out to determine the binding processes of these chemicals within the kinase’s active region. These discoveries are an important step toward the development of novel treatments for cardiovascular illnesses and hypertension, with the potential for more precise and efficient therapeutic interventions in the future.
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