ABSTRACT
Synthesis and antifungal activity of hybrids of thiazolo[4,5-d]pyrimidines with (1H-1,2,4)triazoles are presented. The solubility and lipophilicity of compounds was assessed and it was discovered that compounds with piperazine linker exhibited significant antifungal activity against filamentous and yeast fungi.
Subject(s)
Antifungal Agents/pharmacology , Pyrimidines/pharmacology , Thiazoles/pharmacology , Triazoles/pharmacology , Antifungal Agents/chemical synthesis , Drug Design , Fungi/drug effects , Microbial Sensitivity Tests , Pyrimidines/chemical synthesis , Solubility , Thiazoles/chemical synthesis , Triazoles/chemical synthesisABSTRACT
Aqueous solubility and distribution of ciprofloxacin, enrofloxacin, norfloxacin and levofloxacin antimicrobials drugs in octanol/buffer system has been measured by the isothermal saturation method using buffer solutions pH2.0 and 7.4 in the temperature range of 293.15-313.15K. Thermophysical characteristics for the compounds have been determined by the DSC method. It has been established that the solubility of levofloxacin in these buffers is higher than that of the other fluoroquinolones. HYBOT descriptors for biologically active compounds have been calculated and the impact of the donor-acceptor capacity of the molecules on drugs solubility has been studied. According to the lipophilicity parameter fluoroquinolones are ranged in the following order: enrofloxacin>levofloxacin>ciprofloxacin>norfloxacin. The thermodynamic solubility and distribution functions of the studied compounds have been obtained. The permeability coefficients of the substances through an artificial phospholipid membrane were determined. The drugs with a lower aqueous solubility were estimated to have higher distribution coefficients and membrane permeability.
Subject(s)
Anti-Infective Agents/chemistry , Cell Membrane Permeability , Fluoroquinolones/chemistry , Lipids/chemistry , Anti-Infective Agents/pharmacology , Calorimetry, Differential Scanning , Fluoroquinolones/pharmacology , Solubility , ThermodynamicsABSTRACT
New spiro-derivatives of 1,3-thiazine - potential neuroprotectors have been synthesized. It has been determined that the obtained compounds are biologically active and capable of blocking the glutamate-induced calcium ion uptake into synaptosomes of rat brain cortex. The inhibitory activity of the test substances was shown to depend on the chemical nature and structure of the substituents bound with an exocyclic nitrogen atom. Non-polar alkyl and polar radicals with halogen, oxygen and nitrogen atoms were used as substituents. It is typical of the active spiro-thiazines to have alkyl substituents in ortho- and para-position of the benzene ring. Among the investigated spiro-thiazines it is the derivatives with ethyl- and isopropyl-groups in the aril part of the molecules that are the lead-compounds with a high inhibitory ability. We measured the distribution coefficients of the substances in octanol/buffer and hexane/buffer systems and made conclusions about the ability of the investigated drug-like compounds to penetrate the biological membranes. By using the parabolic model we derived a quadratic equation that allowed us to evaluate quantitatively the inhibitory activity of spiro-thiazines with hydrophobic substituents based on lipophilicity data. We also studied the permeability through the phospholipidic membrane and introduced a correlation equation describing the dependence of the investigated spiro-thiazines activity on the descriptors characterizing the donor-acceptor properties.
Subject(s)
Cell Membrane Permeability/drug effects , Cerebral Cortex/drug effects , Neuroprotective Agents/chemical synthesis , Neuroprotective Agents/pharmacology , Spiro Compounds/pharmacology , Thiazines/pharmacology , Animals , Calcium/metabolism , Cerebral Cortex/cytology , Cerebral Cortex/metabolism , Dose-Response Relationship, Drug , Glutamic Acid/pharmacology , Molecular Structure , Neuroprotective Agents/chemistry , Rats , Spiro Compounds/chemical synthesis , Spiro Compounds/chemistry , Structure-Activity Relationship , Thiazines/chemical synthesis , Thiazines/chemistryABSTRACT
A binary system composed of the liquid crystalline poly(propyleneimine) dendrimer and nematic p-n-pentyloxy-p'-cyanobyphenyl has been studied by thermomicroscopy, scanning calorimetry, and inverse gas chromatography. In this system, there is the columnar phase being stable within broad ranges of temperature and component ratio. Dependences of the retention volumes of various solutes, namely, hydrocarbons, alcohols, and amines, on composition of the sorbents are revealed to exhibit the maximum. Thermodynamic functions of sorption of n-alkanes and n-alcohols on the binary sorbents composed of the said liquid crystals have been calculated specifically. Thermodynamic solute-sorbent compatibility characterized by the activity coefficients of the solutes is dependent on the sorbent composition; namely, it is controlled by counterbalancing of the enthalpy or entropy factors. The nonadditive mode of the solute-sorbent interaction is explained by arising of the microdomain nematic structure enclosed in the columnar structure of the dendrimer.
