Chitosan-Glycolic Acid Gel Modification of Chloride Ion Transport in Mammalian Skin: An In Vitro Study.

Chitosan, a polyaminosaccharide with high medical and cosmetic potential, can be combined with the beneficial properties of glycolic acid to form a gel that not only moisturizes the skin, but also has a regenerative effect. Its involvement in the activation of biochemical processes may be associated with the activity of skin ion channels. Therefore, the aim of the research was to evaluate the immediate (15 s) and long-term (24 h) effect of chitosan-glycolic acid gel (CGG) on the transepithelial electric potential and the transepithelial electric resistance (R) of skin specimens tested in vitro.

Tropinone-Derived Alkaloids as Potent Anticancer Agents: Synthesis, Tyrosinase Inhibition, Mechanism of Action, DFT Calculation, and Molecular Docking Studies.

A new series of hybrid compounds with tropinone and thiazole rings in the structure was designed and synthesized as potential anticancer agents. They were tested against human multiple myeloma (RPMI 8226), lung carcinoma (A549), breast adenocarcinoma (MDA-MB-231), and mouse skin melanoma (B16-F10) cell lines. Toxicity was tested on human normal skin fibroblasts (HSF) and normal colon fibroblasts (CCD-18Co).

Discovery of tropinone-thiazole derivatives as potent caspase 3/7 activators, and noncompetitive tyrosinase inhibitors with high antiproliferative activity: Rational design, one-pot tricomponent synthesis, and lipophilicity determination.

We have designed novel tropinone-thiazole derivatives that showed high antiproliferative activity against a variety of cancer cell lines via caspase 3/7 activation mechanism. Among the derivatives, compounds 3b-3h were found to exhibit high activity against human leukemia (MV4-11), human lung carcinoma (A549), human breast carcinoma (MCF-7), and skin melanoma (B16-F10) cancer cell lines, with IC values of 5.43-11.

Triazene salts: Design, synthesis, ctDNA interaction, lipophilicity determination, DFT calculation, and antiproliferative activity against human cancer cell lines.

Synthesis, characterization and investigation of antiproliferative activity of nine triazene salts against human cancer cells lines (MV-4-11, MCF-7, JURKAT, HT-29, Hep-G2, HeLa, Du-145 and DAUDI), and normal human mammary epithelial cell line (MCF7-10A) is presented. The structures of novel compounds were determined using H and C NMR, and GC-APCI-MS analyses. Among the derivatives, compound , , and has very strong activity against biphenotypic B myelomonocytic leukemia MV4-11, with IC values from 5.

Synthesis, antimicrobial and anticonvulsant screening of small library of tetrahydro-2H-thiopyran-4-yl based thiazoles and selenazoles.

Synthesis and investigation of antimicrobial activity of 22 novel thiazoles and selenazoles derived from dihydro-2H-thiopyran-4(3H)-one are presented. Additionally, anticonvulsant activity of six derivatives is examinated. Among the derivatives, compounds 4a-f, 4i, 4k, 4 l, 4n, 4o-s and 4v have very strong activity against Candida spp.

Synthesis and anticonvulsant activities of novel 2-(cyclopentylmethylene)hydrazinyl-1,3-thiazoles in mouse models of seizures.

Synthesis, characterization and investigation of in vivo anticonvulsant activities of 13 novel cyclopentanecarbaldehyde-based 2,4-disubstituted 1,3-thiazoles are presented. Their structures were determined using (1)H and (13)C NMR, FAB(+)-MS, HRMS and elemental analyses. The results of anticonvulsant screening reveal that seven intraperitoneally administered compounds: 3a, 3b, 3d, 3e, 3f, 3k and 3m containing F-, Cl-, Br-, CF3-, CH3- and adamantyl substituents demonstrated significant anticonvulsant activity in the pentylenetetrazole model with median effective doses (ED50) ≤ 20 mg/kg, respectively, which was approximately seven-fold lower than that reported for the reference drug, ethosuximide.

Synthesis, Antibacterial Activity, Interaction with Nucleobase and Molecular Docking Studies of 4-Formylbenzoic Acid Based Thiazoles.

Background: Synthesis, characterization and investigation of antibacterial activity of ten novel Schiff base derivatives of 4-formylbenzoic acid is presented. Their structures were determined using 1H and 13CNMR, EI(+)-MS and elemental analyses. Additionally, DFT calculations of interaction energies in complexes of the novel drugs and DNA bases are carried out.

Discovery and evaluation of efficient selenazoles with high antifungal activity against Candida spp.

Synthesis, characterization and investigation of antifungal and antibacterial activities of fourteen 2,4- disubstituted 1,3-selenazoles is presented. Their structures were determined using (1)H and (13)C NMR, FAB MS and HRMS analyses. Among the derivatives, compounds 5, 6, 8, 9, 12, 13 and 15 had very strong activity against reference strains of C.

Synthesis and in vitro antiproliferative activity of thiazole-based nitrogen mustards: the hydrogen bonding interaction between model systems and nucleobases.

Synthesis, characterization and investigation of antiproliferative activity of eight thiazole-based nitrogen mustard against human cancer cells lines (MV4-11, A549, HCT116 and MCF-7) and normal mouse fibroblast (BALB/3T3) are presented. Their structures were determined using NMR, FAB MS, HRMS and elemental analyses. Among the derivatives, 3a, 3b, 3e and 3h were found to exhibit high activity against human leukemia MV4-11 cells with IC50 values of 0.

Synthesis, in vitro biological screening and molecular docking studies of novel camphor-based thiazoles.

Synthesis, characterization and investigation of antibacterial and antifungal activities of twelve camphor based 2,4-disubstituted 1,3-thiazoles is presented. Their structures were determined using NMR, IR, FAB MS and HRMS analyses. Among the derivatives, 3i and 5 were found to exhibit antifungal and antibacterial activities comparable to that of fluconazole and ciprofloxacin against yeast belonging to Candida spp.

[Classical oxazaphosphorines--metabolism and therapeutic properties--new implications].

Cyclophosphamide (CPA) and ifosfamide (IFO) belong to oxazaphosphorine drugs and for a few decades have been widely used for treatment of solid tumours and haematological malignancies. Both drugs are administered in pharmacologically inactive form and require metabolic activation by cytochrome P-450 (CYP). Metabolic transformations taking place under the action of specific CYP isoenzymes lead to the formation of therapeutically essential metabolites and some toxic compounds affecting quality of therapy.

Acyloxymethyl esters of isophosphoramide mustard as new anticancer prodrugs.

A series of new prodrugs: [bis(2-chloroethylamino)phosphoryloxy]methyl acetate, [bis(2-chloroethylamino)phosphoryloxy]methyl pivalate and [bis(2-chloroethylamino)phosphoryloxy]methyl benzoate, was obtained in the reaction of isophosphoramide mustard (iPAM) with the corresponding acyloxymethyl halides. The cytotoxic activity of these new compounds is also shown. All compounds were highly active in the inhibition of cancer cell proliferation against the human lung (A594), prostate (PC-3) and breast (MCF-7) cancer cell lines.

[Increased urinary excretion of the neurotoxic side-chain metabolites of ifosphamide in children with polymorphism of the glutathione S-transferases genes].

Unlabelled: From 5% to 30% of children treated with ifosphamide (IF) develop symptoms of neurotoxicity due to toxic metabolites of the drug: 2- and 3- dechloroifosphamide (2- and 3-DCIF) and chloracetaldehyde (CAA), which cause glutathione depletion in cells. The aim of the study is to establish the influence of polymorphism of genes encoding for glutathione S-transferases classes pi (GSTP1), mi (GSTM1) and theta (GSTT1) on frequency of neurotoxicity of IF and amounts of toxic metabolites of the drug excreted in urine.

Material And Methods: Neurotoxicity of IF was assessed in 76 children (38 girls and 38 boys), aged 9 to 210 months with diffrent kinds of neoplasms.

Ifosfamide. Metabolic studies, new therapeutic approaches and new analogs.

Ifosfamide (IFO), an oxazaphosphorine-type anticancer alkylating agent, was found to be particularly useful in the treatment of a wide variety of neoplasm in adults and children. IFO is a positional isomer of cyclophosphamide (CPA) and was introduced into clinical practice in the 80s and has recently attracted much attention. Therapeutic application of high-dose IFO is limited by several side-effects; among them neurotoxicity and nephrotoxicity give the greatest concern.

Role of GSTM1, GSTP1, and GSTT1 gene polymorphism in ifosfamide metabolism affecting neurotoxicity and nephrotoxicity in children.

The aim of this study was to evaluate the impact of GSTM1, GSTT1, and GSTP1 gene polymorphism on urinary excretion of unchanged ifosfamide, 2-dechloroethylifosfamide (2DCIF), and 3-dechloroethylifosfamide (3DCIF) with regard to the incidence of ifosfamide-related nephrotoxicity and neurotoxicity in children. The study comprised 76 children (38 girls, 38 boys) ages 9.84 to 210 months who were being treated for various malignant diseases with ifosfamide.

Synthesis of nucleoside alpha-thiotriphosphates via an oxathiaphospholane approach.

[reaction: see text]. Nucleoside 5'-O-(alpha-thiotriphosphates) were obtained in reactions of the appropriate nucleoside 5'-O-(2-thio-1,3,2-oxathiaphospholanes) with pyrophosphate in the presence of DBU. The presented method allows also for preparation of alpha-seleno congeners and corresponding alpha-modified diphosphates.

[Oxazaphosphorinane drugs. New analogues, metabolic studies, and therapeutic approaches].

Recent studies on oxazaphosphorinane drugs, with the main focus on those carried out in Poland, are briefly reviewed. Research leading to the introduction of the new antitumor drug (S)-(-)-bromofosfamide are presented. The utility of phosphorus nuclear magnetic resonance in studies of ifosfamide metabolism and an application of analogues of the final, active metabolite of this drug in gene therapy are shown.

Phosphate prodrugs of isophosphoramide mustard.

Dibenzylphosphorobenzyl and phosphorobenzyl analogues of isophosphoramide mustard, an active metabolite of ifosfamide were synthesized. Phosphorobenzyl analogue posseses stronger cytotoxic activity than isophosphoroamide mustard against the cells of several cancer cell lines suggesting the possibility of the use of this compound in Gene-Directed Enzyme-Prodrug Therapy (GDEPT).

Analysis of the urinary excretion of ifosfamide and its N-dechloroethylated metabolites in children using 31P-NMR spectroscopy.

Amounts of ifosfamide (CAS 3778-73-2) and its N-dechloroethylated metabolites excreted in the urine were measured using 31P-NMR spectroscopy in 26 cancer children treated with this drug. Strong inter-patient variation in levels of these compounds were found. These differences were independent from patients age, body surface area, and sex, the dose of the drug, suggesting genetic base of observed variations in ifosfamide metabolism.

A new method for distinguishing between enantiomers and racemates and assignment of enantiomeric purity by means of solid-state NMR. Examples from oxazaphosphorinanes.

It is shown that enantiomers and racemates that have identical isotropic NMR chemical shift as well as anisotropic chemical-shift tensor parameters can be easily distinguished by means of the ODESSA (One Dimensional Exchange Spectroscopy by Sideband Alternation) technique. The method is based on the fact that the molecular symmetries and packing of enantiomers and racemates are usually significantly different. The power of the proposed approach is demonstrated by employing as model compounds P-chiral oxazaphosphorine derivatives, which are widely used in clinical oncology.

Isophosphoramide mustard analogues as prodrugs for anticancer gene-directed enzyme-prodrug therapy (GDEPT).

Two types of prodrugs, benzyl analogues of isophosphoramide mustard (iPAM), activated by cytochrome P450, and acylthioethyl analogues, activated by esterases, were designed. In contrast to iPAM that hydrolyse rapidly, the examined compounds are stable in phosphate-buffered saline and Tris buffer. Benzyl analogues of iPAM are poor substrates for cytochrome P450, are not cytotoxic and posses no antitumour activity.

Synthesis and antitumour activity of stereoisomers of 4-hydroperoxy derivatives of ifosfamide and its bromo analogue.

Racemic mixtures and laevorotatory enantiomers of cis- and trans-4-hydroperoxyifosfamide and 4-hydroperoxybromofosfamide possess high antitumour activity both in vitro and in vivo. However, no major differences in biological activity were observed among these stereoisomers.

Studies on the side-chain hydroxylation of ifosfamide and its bromo analogue.

Deutero-substituted (alpha,alpha,alpha',alpha'-tetradeuterated) derivatives of ifosfamide (IF-d(4)) and its bromo analogue were synthesised. In vitro metabolic studies showed that microsomal hydroxylation of IF-d(4) is slower than for unlabelled compound, suggesting that kinetic isotope effect operates during those transformations. At the same time deutero-substituted derivatives are more active against L1210 leukaemia in mice than unlabelled compounds, suggesting a negative role of side-chain hydroxylation metabolic pathways in the anticancer activity of ifosfamide and its analogues.