58228-93-6Relevant articles and documents
Synthesis and Binding Studies of Trishomocubanes: Novel Ligands for ? Binding Sites
Liu, Xiang,Kassiou, Michael,Christie, MacDonald J.
, p. 653 - 656 (1999)
Five new analogues of the ?2-selective trishomocubane N-(3'-fluorophenyl)methyl-4-azahexacyclo[5.4.1.02,6.03,10.05,9.08,11]dodecan-3-ol (2) have been synthesized and assessed for their affinities at b
Polycyclic amines as chloroquine resistance modulating agents in Plasmodium falciparum
Joubert, Jacques,Kapp, Erika,Taylor, Dale,Smith, Peter J.,Malan, Sarel F.
, p. 1151 - 1155 (2016)
Pentacycloundecylamines (PCUs) and adamantane amines, such as NGP1-01 (1) and amantadine, have shown significant channel blocking activities. They are postulated to act as chemosensitizers and circumvent the resistance of the plasmodia parasite against chloroquine (CQ) by inhibiting the p-glycoprotein efflux pump and enabling the accumulation of CQ inside the parasite digestive vacuole. Twelve polycyclic amines containing either a PCU or adamantane amine moiety conjugated to different aromatic functionalities through various tethered linkers were selected based on their channel blocking abilities and evaluated as potential chemosensitizers. Compounds 2, 4, 5 and 10 showed significant voltage-gated calcium channel (VGCC) blocking ability (IC50?=?0.27–35?μM) and were able to alter the CQ IC50 in differing degrees (45–81%) in the multidrug resistant Plasmodium falciparum Dd2 isolate. Among them, the PCU-dansyl amine compound (4) displayed the best potential to act as a chemosensitizer against the Dd2 strain at a 1?μM concentration (RMI?=?0.19) while displaying moderate antiplasmodial activity (Dd2 IC50?=?6.25?μM) and low in vitro cytotoxicity against a mammalian cell line (CHO, IC50?=?119?μM). Compounds 2 and 10 also showed some promising chemosensitizing abilities (RMI?=?0.36 and 0.35 respectively). A direct correlation was found between the VGCC blocking ability of these polycyclic amines and their capacity to act as CQ resistance modulating agents.
Design, synthesis and evaluation of pentacycloundecane and hexacycloundecane propargylamine derivatives as multifunctional neuroprotective agents
Zindo, Frank T.,Malan, Sarel F.,Omoruyi, Sylvester I.,Enogieru, Adaze B.,Ekpo, Okobi E.,Joubert, Jacques
, p. 83 - 94 (2018/12/04)
The multifactorial pathophysiology of neurodegenerative disorders remains one of the main challenges in the design of a single molecule that may ultimately prevent the progression of these disorders in affected patients. In this article, we report on twelve novel polycyclic amine cage derivatives, synthesized with or without a propargylamine function, designed to possess inherent multifunctional neuroprotective activity. The MTT cytotoxicity assay results showed the SH-SY5Y human neuroblastoma cells to be viable with the twelve compounds, particularly at concentrations less than 10 μM. The compounds also showed significant neuroprotective activity, ranging from 31% to 61% at 1 μM, when assayed on SH-SY5Y human neuroblastoma cells in which neurodegeneration was induced by MPP+. Calcium regulation assays conducted on the same cell line showed the compounds to be significant VGCC blockers with activity ranging from 26.6% to 51.3% at 10 μM; as well as significant NMDAr antagonists with compound 5 showing the best activity of 88.3% at 10 μM. When assayed on human MAO isoenzymes, most of the compounds showed significant inhibitory activity, with compound 5 showing the best activity (MAO-B: IC50 = 1.70 μM). Generally, the compounds were about 3–52 times more selective to the MAO-B isoenzyme than the MAO-A isoenzyme. Based on the time-dependency studies conducted, the compounds can be defined as reversible MAO inhibitors. Several structure activity relationships were derived from the various assays conducted, and the compounds’ possible putative binding modes within the MAO-B enzyme cavity were assessed in silico.
NMR analysis of some pentacycloundecanedione derivatives
Kruger, Hendrik G.,Ramdhani, Reshika
, p. 71 - 74 (2007/10/03)
The complete NMR elucidation of four pentacycloundecanedione (PCUdione) derivatives is described. Major proton shifts occur when additions are performed on the carbonyl carbons. Some of the carbon signals are also transposed. Despite the fact that the signals of the methine protons on the cage skeleton experience major overlapping, complete assignment of all the protons is possible through 2D NMR experiments. Nuclear Overhauser Effect Spectroscopy (NOESY) interaction between the two nonequivalent bridge protons and protons on the cage skeleton proved to be a very convenient handle to elucidate the structures of the PCU compounds. A density functional theory (DFT) optimization [B3LYP/6-31+G(d)] of two possible ketal conformations was used to assist with the elucidation of the asymmetric ketal structure.
