Anthracene‐Walled Acyclic CB[n] Receptors: in vitro and in vivo Binding Properties toward Drugs of Abuse

Abstract

We report studies of the interaction of six acyclic CB[n]‐type receptors toward a panel of drugs of abuse by a combination of isothermal titration calorimetry and 1H NMR spectroscopy. Anthracene walled acyclic CB[n] host (M3) displays highest binding affinity toward methamphetamine (Kd=15 nM) and fentanyl (Kd=4 nM). Host M3 is well tolerated by Hep G2 and HEK 293 cells up to 100 μM according to MTS metabolic and adenylate kinase release assays. An in vivo maximum tolerated dose study with Swiss Webster mice showed no adverse effects at the highest dose studied (44.7 mg kg−1). Host M3 is not mutagenic based on the Ames fluctuation test and does not inhibit the hERG ion channel. In vivo efficacy studies showed that pretreatment of mice with M3 significantly reduces the hyperlocomotion after treatment with methamphetamine, but M3 does not function similarly when administered 30 seconds after methamphetamine.

Macrocyclic Neutralizer to Polybrene via Direct Host–Guest Complexation

“…Pharmaceutical agents and toxic substances have a significant impact, positive and negative, on human health. − Efforts to mitigate the side effects of pharmaceutics and counteract the life threating effects of toxins can occur by artificial detoxification methods, such as blood dialysis, gastric lavage, and the administration of active charcoal and antidotes. − Supramolecular hosts including cyclodextrins, calixarenes, acyclic cucurbiturils, and pillararenes have been used as in vivo sequestration agents for neuromuscular blockers, − anesthetics, and heparin anticoagulants. , Polybrene, known as hexadimethrine bromide (HB), was first introduced to clinical practice in 1954 to reverse heparin anticoagulation after cardiopulmonary bypass . Nowadays, it is widely used in gene therapy and laboratory gene transfer to increase the efficiency of virus infection. , For example, viral culture medium was supplemented with HB, which can increase virus adsorption by target cells by approximately 10-fold .…”

“…1−3 Efforts to mitigate the side effects of pharmaceutics and counteract the life threating effects of toxins can occur by artificial detoxification methods, such as blood dialysis, gastric lavage, and the administration of active charcoal and antidotes. 4−6 Supramolecular hosts including cyclodextrins, calixarenes, acyclic cucurbiturils, and pillararenes have been used as in vivo sequestration agents for neuromuscular blockers, 7−9 anesthetics, 10 and heparin anticoagulants. 11,12 Polybrene, known as hexadimethrine bromide (HB), was first introduced to clinical practice in 1954 to reverse heparin anticoagulation after cardiopulmonary bypass.…”

A general supramolecular adjuvant for pesticides based on host–guest recognition

“…Host–guest chemistry paves an alternative way to develop new solubilizing adjuvants. Significant modulation in the physicochemical properties and biological profiles of molecules can be achieved via host–guest recognition 7,8 . Macrocyclic hosts, including crown ethers, cyclodextrins, calixarenes, cucurbiturils, and pillarenes, have attracted intense attention due to their inherent complex‐forming ability 9–12 .…”

“…Significant modulation in the physicochemical properties and biological profiles of molecules can be achieved via host-guest recognition. 7,8 Macrocyclic hosts, including crown ethers, cyclodextrins, calixarenes, cucurbiturils, and pillarenes, have attracted intense attention due to their inherent complex-forming ability. [9][10][11][12] These macrocycles contain special cavity structures that can act as molecular containers to encapsulate drug guests to improve drug solubility, enhance drug stability, increase drug bioavailability, reduce side effects, and control release.…”