In this report SULFUXAMIDE derivatives of CALIXARENE has been choosed from as capable molecular hosts. First of all chlorosulfunation reaction has been done an para teri butyle calix [4]arene and the obtained product has been reacted with para phenyle azo benzen and tetra aza SULFUXAMIDE derivative of CALIXARENE was prepared.The obtained product has been characterized by FTIR, 13CNMR, 1HNMR and TOF-MS techniques. The results showed the obtained product has stable cone conformation. The CALIXARENE with large cavities and stable conformations can be used as capable molecular receptor in host-geant chemistry.

The oxidative stress causes many diseases in human, therefore antioxidants have a special position in the medicinal chemistry. Tyrosol is an important antioxidant with a plenty of biological properties. There are many strategies such as clustering single drug units in order to develop new drugs. The cluster effect can increase drug effects relative to single drug unit. Calixtyrosol is the novel cluster of tyrosol that shows a more effective antioxidant activity than single tyrosol. In fact, tyrosol can be considered as 1/4 of the cluster.Four hydroxyethyl moieties have been grafted at the upper rim of the calix [4] arene in allsyn orientation, giving novel agent in the field of antioxidant agents. Free radical scavenging tests were determined by the 2, 2-diphenyl-1-picrylhydrazyl radical in methanol for four antioxidants: calixtyrosol, tyrosol, hydroxytyrosol and 3, 5-di-tert-buty l-4-hydroxytoluene to compare their antioxidant activity. Free radical scavenging test showed that calixtyrosol has enhanced antioxidant activity in comparison to the corresponding single tyrosol unit (> 5 fold), it has even more active than the other test antioxidants (2 fold). Presumably, it is attributed to tethering and arraying of four impacted tyrosol units, which make a synergistic effect in interactions with radicals for creating effective radical scavenging activity. This method is in debt of synergistic effect, tethering and arraying of single units in the cluster structure.

In this paper, the synthesis and free-radical scavenging capacity of novel calix[4]arenebased cluster of paracetamol was reported. The phenolic structures of acetaminophen and calix[4]arene prompted us for designing a synthetic route for calix[4]arene-based cyclic tetramer of paracetamol. The present chalice-shaped cluster is the first example of CALIXARENE/ acetaminophen hybrid and paracetamol can be considered as ¼ of the synthetic cyclic tetramer. Free-radical scavenging tests were determined by the 2, 2-diphenyl-1-picrylhydrazyl radical in methanol. The results of antiradical-testing showed the enhanced free-radical scavenging capacity (~ 10-fold) for the prepared chaliced-shaped cluster with respect to the corresponding single therapeutic drug unit (acetaminophen). It is maybe attributed to the multivalency, spatial preorganization, and synergistic effect of four impacted drug units in the cluster structure (clustering effect).

The first examples of CALIXARENE ionic liquids 3 and 6 with 3D-shaped cavities were obtained in high yields by reacting calix [4]arene or thiacalix[4]arene with 1,6-dibromohexane and then refluxing in 1-methylimidazole. The experiments of phase transfer catalysis in water suggested that they possessed excellent catalytic properties of aromatic nucleophilic substitution reaction and benzyl nucleophilic substitution. The optimized yields of product in catalytic reaction were as high as approximate 97% under mild reaction conditions. The cavities of CALIXARENE skeleton played the crucial roles in catalysis and the stable cone conformation was favorable for catalysis.

Since melanocytes are the origin of melanoma and some skin disorders such as melasma, they are important cells from the perspective of medicinal chemistry. Therefore, a medication that can simultaneously overcome these diseases will be a successful potential therapeutic agent. Arbutin with phenolic structure is a powerful natural anti-tyrosinase agent. Hence, the phenolic structure of this drug, prompted us to design its novel calix [4]arene-based cluster. Therefore, the present study reports the synthesis and in-vitro bio-activities of cyclic tetramer of arbutin in comparison to its simple drug unit as the reference medication. The in-vitro biological results showed amplified anti-tyrosinase (6-fold) and anti-melanoma (27-fold) activities, in addition to more aqueous solubility (8-fold) for this cluster in relation to arbutin. Therefore, compared to arbutin, more bioactive cluster can be considered as a novel water-soluble melanogenesis inhibitor with high anti-melanoma activity.

Mexiletine as the first choice drug in myotonia treatment is a chiral sodium channel blocker clinically used in its racemic form. The phenolic structure of this drug, prompted us to design its novel calix[4]arene-based cluster in a chalice-shaped structure. Therefore, the present study reports the synthesis and in-vitro anti-myotonic activity of the chalice-shaped cluster of mexiletine (namely calixmexitil) in comparison to its simple drug unit (mexitil) as the reference medication. The synthetic route included chemical modification of the calix[4] arene structure by grafting four 2-aminopropoxy moieties at the lower rim of the scaffold. Electrophysiological tests were performed for the determination of test compounds abilities to act as sodium channel blockers in inhibiting sodium currents (in use-dependent manner) in single skeletal muscle fibers. The experimental results showed an amplified (10-fold) potency in producing phasic block as an indication of the anti-myotonic activity and improved (3-fold) potency in producing use-dependent block for the cluster (calixmexitil) in relation to its monomer (mexiletine). The potency in producing phasic block and use-dependent block are two main factors to describe dose range, drug affinity, and side effects of an antimyotonic agent. Therefore, compared to mexiletine, calixmexitil with these improved factors can be considered as a “ selective” anti-myotonic agent with low dose range. These improved pharmaceutical effects are maybe attributed to clustering effect and improved interaction of four impacted mexiletine units of the cluster with the sodium channels’ structure in skeletal muscle fibers.

Molecular recognition involves the association of molecular through non-covalent interactions such as vanderwaals force, hydrogen bounds, electrostatic interactions, and so on that often called host-guest interactions. Researchers are concerned about CALIXARENEs with regards to having bowl-shaped molecules and their ability to performing molecular capsules. These capsules can be encapsulated biological guest molecules. In this review, examples of the organic-functionalized CALIXARENEs on their upper or lower rims have been collected. In these reports, the functionalized CALIXARENEs were used as ligand or receptor to recognize ions and biomacromolecules such as aminoacids, proteins, DNA, and NADH. The florescence spectroscopy method has been applied to study host-guest interactions due to its simplicity.

Calix(6)arene hydroxamic acids (III) are synthesised for the first time by reacting calix(6) arene acid chloride(II) with substituted hydroxylamines at low temperature in the presence of sodium bicarbonate. The p-carboxycalix(6)arene(I) is obtained by an acid catalysed condensation reaction of p-hydroxybenzoic acid and formaldehyde. These CALIXARENEs are characterised by melting point, UV, IR, 1H NMR and mass spectra. The thermodynamic ionization constants of CALIXARENE hydroxamic acids have been determined by a pH titration technique in dioxane-water media.