Athanasia Varvaresou

Synthesis, lipophilicity and biological evaluation of indole-containing derivatives of 1,3,4-thiadiazole and 1,2,4-triazole

3-[(2-Methyl-1H-3-indolyl) methyl]-4-aryl-4, 5-dihydro-1H-1,2,4-triazole-5-thiones 6a-c and their respective N-¿5-[2-methyl-1H-3-indolyl) methyl]-1,3,4-thiadiazol-2-yl¿-N-arylamines 7a,b have been prepared. The antidepressant profile of 6a,c and 7a was studied on mice with respect to that of the analogous 3-(1H-1-indolylmethyl)-4-aryl-4,5-dihydro-1H-1,2,4-triazole-5-thio nes 1a-c and the respective N-¿5-[(2-methyl-1H-3-indolyl) methyl]-1,3,4-thiadiazole-2-yl¿-N-arylamines 2a-c, the synthesis and antimicrobial potency of which we have recently reported. Behavioral effects, induced by the members of both series, in conjunction with their activity in some specific tests (forced swim, pentetrazole convulsions) on mice, show that these derivatives cross the blood-brain barrier and could develop an antidepressant activity comparable to that of imipramine. Blood-brain barrier penetration is also supported by the lipophilicity data obtained for all analogs.

Percutaneous absorption of organic sunscreens

The increased awareness of protection against skin cancer has led to a rise in the use of topically applied chemical sunscreen agents. There is a concern about the systemic absorption of organic filters in sunscreen formulations. The present study briefly reviews theoretical models for the prediction of the percutaneous penetration of the organic molecules and the accepted methods for the in vitro and in vivo evaluations of the penetration. The influence of the vehicle and the formulation viscosity on the penetration of sunscreens are examined. The development of novel methods for the minimization of sunscreen absorption is also discussed.

Molecular modeling study of intercalation complexes of tricyclic carboxamides with d(CCGGCGCCGG)2 and d(CGCGAATTCGCG)2

AbstractTricyclic dyes with different mesoatoms such as xanthenes (fluorescein, eosin) anthracenes and acridines (proflavine) approved by the Food and Drug Administration (FDA) for use in foods, pharmaceuticals and cosmetic preparations interact with DNA, and some of them do so through intercalation. Hyperchem 7.5, Spartan 04, Yasara 10.5.14 program packages and molecular modeling, molecular mechanics and dynamics techniques with the oligonucleotides d(CCGGCGCCGG)2 and d(CGCGAATTCGCG)2 were utilized in order to examine the mode of binding to DNA of a range of tricyclic carboxamides bearing N,N-dimethylaminoethyl side chain, i.e., 9-amino-DACA, anthracene, acridine-1-carboxamide, acridine-4-carboxamide (DACA), azacridine, phenazine, pyridoquinoxaline, oxopyridoquinoxaline, phenoxazine and xanthenone or N,N-dimethylaminobutyl moiety, i.e., phenazine and acridine. The bicyclic quinoline-8-carboxamide was also examined for comparison reasons. On the basis of our data, prerequisite for the interaction between protonated N,N-dimethylaminoethyl moiety and guanine is the formation of only one internal hydrogen bond between carboxamide and peri NH + in the case of 9-amino-DACA or peri N in the cases of DACA, azacridine, phenazine and pyridoquinoxaline. The presence of an additional internal hydrogen bond between oxygen carboxamide and protonated N,N-dimethylamino group in the cases of tricyclic systems bearing peri NH (phenoxazine) or O (xanthenone) group, prevents the interaction between side chain and guanine. Also, the formation of one internal hydrogen bond between oxygen carboxamide and protonated N,N-dimethylamino group inhibits the interaction between side chain and guanine in the case of acridine-1-carboxamide. Our findings are in accordance with previously reported results obtained from the kinetic studies of the binding of acridine and related tricyclic carboxamides to DNA. FigureStructures of tricyclic carboxamides studied.

New aza-thioxanthones: Synthesis and cytotoxicity

Abstract A new series of aza-thioxanthones has been synthesized and tested for in vitro cytotoxicity in a number of cell lines. Almost all the compounds were found to exhibit significant cytotoxicity in the leukemic MOLT-4 line, whereas some of them showed pronounced activity in the non-small lung cancer cell line HOP-92.

Novel imidazothioxanthones: Synthesis, DNA binding and cytotoxicity

Abstract A new class of DNA-binding ligands ( 10a-f ) has been synthesized and examined for DNA-binding affinity using thermal denaturation and for in vitro cytotoxicity in a number of cell lines. All the compounds were found to possess significant DNA-binding affinity which correlates with in vitro cytotoxicity across eight cell lines.

Development and validation of an ion-pair RP-HPLC method for the determination of oligopeptide-20 in cosmeceuticals

Oligopeptide-20 is a growth-factor mimicking peptide used in cosmeceuticals. This article describes the development and validation of an ion-pair reversed-phase liquid chromatography method that allows, after liquid-liquid extraction, the quantification of oligopeptide-20 in cosmetic creams. Chromatographic separation was achieved on a cyanopropyl Hypersil analytical column (100 mm × 2.1 mm i.d., 5 μm particle size), using a mobile phase of acetonitrile-heptafluorobutyric acid (pH=2.5, 9.0 mM) (70:30, v/v) containing 0.045% diethylamine at a flow rate of 0.50 mL min(-1). Ultraviolet (UV) spectrophotometric detection at 225 nm was used. The method had linear calibration curve over the range 1.35-4.95 μg mL(-1) for oligopeptide-20. The intra- and inter-day RSD values were less than 3.3%, while the relative percentage error, %E(r), was less than 1.9. The developed method was applied successfully to the quality control of a cosmetic cream containing 0.003% (w/w) oligopeptide-20.

A Critical Appraisal of logP Calculation Procedures Using Experimental Octanol-Water and Cyclohexane-Water Partition Coefficients and HPLC Capacity Factors for a Series of Indole Containing Derivatives of 1,3,4-Thiadiazole and 1,2,4-Triazole

The accumulation of several heteroatoms in hybrid molecules may affect the safe prediction of lipophilicity, while such compounds may differentiate in their hydrogen bonding capability, also important in the manifestation of drug action. The title compounds, which belong to the general types 1,2,3,4 (Figure 1) have shown CNS and antimicrobial activities.1,2 In this study their lipophilicity was investigated and compared to the values obtained by different calculative procedures. Their hydrogen bonding capability was also assessed through the ΔlogP approach.3