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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

The glycosylation of 1,3,4-oxadiazole-2-thiones has been performed with peracetylated β-pyranosyl bromide in the presence of potassium carbonate. Deprotection of acetylated thioglycosides was necessary for increasing their antibacterial effects. The structures of nucleosides were confirmed by ¹H NMR, 13C NMR and HRMS. The anomeric protons of nucleosides c1-4 were assigned to the doublet, confirming the β-configuration. The synthesized compounds were tested for their antimicrobial activity against Acinetobacter calcoaceticus (Gram-negetive) strain in-vitro in comparison with Ampicillin as a reference drug which is normally used for treating such infections. The synthetic compounds showed different inhibition zones against tested bacterial strain. Thioglycoside derivatives of 1,3,4-oxadiazole-2-thiones (c set) were more active against Acinetobacter calcoaceticus ATCC 23055 than "parent" 1,3,4-oxadiazole-2-thiones (a set), confirming the relation between glyco-conjugation and increasing of antiproliferative activity of antibiotic agents. The best result belonged to nucleoside bearing 2-furyl moiety in its heterocyclic nucleus (c4). The existence of m-PhNO2 group as Ar in structures of a set and their corresponding sugar derivatives decreased the antibacterial activity of them in comparison with the rest of synthetic compounds. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The condensation reaction of 5-(4-aminophenyl)-4-phenyl-1,2,4-triazole-3-thione with salicylaldehyde, 4-hydroxybenzaldehyde, 5-chlorosalicylaldehyde, 5-bromosalicylaldehyde, 2-nitrobenzaldehyde, 3-nitrobenzaldehyde, 4-nitrobenzaldehyde and 4-methoxybenzaldehyde in methanol results in series of new Schiff bases. The structure of Schiff bases were confirmed by 1H NMR, 13C NMR, IR and mass spectroscopy. The synthesized compounds were tested for their antimicrobial activity against bacterial (Gram negative and Gram positive) strains in-vitro. The synthetic compounds showed different inhibition zones against tested bacterial strains. All compounds showed significant antiproliferative activity against Acinetobacter calcoaceticus ATCC 23055. In detail, Entrococcus faecalis (Gram positive) was resistant to all prepared compounds, whereas, A. calcoaceticus (Gram negative) was sensitive to all compounds especially 5c, 5d and 4. S. aureus (Gram positive, relatively resistant to antimicrobials) showed limited sensitivity to only 5c and 5d, and it was resistant to all other compounds and only 5c exhibited low activity against P. aeruginosa (Gram negative). The best results belonged to 5c that showed high activity against A. calcoaceticus (33 mm) as well as S. aureus (20 mm). [ABSTRACT FROM AUTHOR]