Giorgia Miolo

Bio: Giorgia Miolo is an academic researcher from University of Padua. The author has contributed to research in topics: Furocoumarin & Thymine. The author has an hindex of 16, co-authored 61 publications receiving 985 citations.

Gold(III) dithiocarbamate derivatives for the treatment of cancer: solution chemistry, DNA binding, and hemolytic properties.

Abstract: Gold(III) compounds are emerging as a new class of metal complexes with outstanding cytotoxic properties and are presently being evaluated as potential antitumor agents. We report here on the solution and electrochemical properties, and the biological behavior of some gold(III) dithiocarbamate derivatives which have been recently proved to be one to 4 orders of magnitude more cytotoxic in vitro than the reference drug (cisplatin) and to be able to overcome to a large extent both intrinsic and acquired resistance to cisplatin itself. Their solution properties have been monitored in order to study their stability under physiological conditions; remarkably, they have shown to undergo complete hydrolysis within 1 h, the metal center remaining in the +3 oxidation state. Their DNA binding properties and ability in hemolyzing red blood cells have been also evaluated. These gold(III) complexes show high reactivity toward some biologically important isolated macromolecules, resulting in a dramatic inhibition of both DNA and RNA synthesis and inducing DNA lesions with a faster kinetics than cisplatin. Nevertheless, they also induce a strong and fast hemolytic effect (compared to cisplatin), suggesting that intracellular DNA might not represent their primary or exclusive biological target.

The Photodegradation of Quercetin: Relation to Oxidation

Abstract: The photostability of quercetin in alcoholic solutions was studied. Both UVA and UVB light induced degradation of quercetin, yielding a single product 1 deriving from oxidation and addition of an alcohol molecule to the 2,3 double bond. The same mechanism operated when quercetin was dissolved in alkaline solutions, and again a product 2 due to oxidation and addition of water was characterized. Comparison with quercetin analogs confirmed that, despite the presence of five hydroxy groups in quercetin, those in positions 3, 3', and 4' are mainly involved in the antioxidant activity of the compound , as well as in its photolability.

Excited-state properties and in vitro phototoxicity studies of three phenothiazine derivatives.

Abstract: This work concerns a combined photophysical, photochemical and photobiological study of three drugs (psychotherapeutic agents) of the phenothiazine series: perphenazine, fluphenazine hydrochloride and thioridazine hydrochloride. The excited-state properties were first investigated by stationary and time-resolved fluorimetry and by laser flash photolysis. The spectral description was assisted by quantum-mechanical calculations with the INDO/1-CI method. In organic media the lowest excited singlet state was found to decay by fluorescence (small quantum yield) and mainly by intersystem crossing to the lowest triplet state, which is responsible for oxygen photosensitization (high yields of singlet oxygen production) and photodegradation. A further decay pathway in aqueous solutions was the photoionization process, which led to the formation of the phenothiazine radical cations and the solvated electron. After the preliminary study of the photobehavior in organic solvents and in water, the phototoxicity of the three drugs was investigated on various biological substrates through a series of in vitro assays under UVA irradiation. Photohemolysis of mouse erythrocytes and phototoxicity on cultured murine fibroblasts were observed for all three compounds. Lipid photoperoxidation was then investigated using linoleic acid as the unsaturated lipid model and isolated red blood cell membranes. The drug-induced photodamage was also evaluated on proteins by measuring the photosensitizing cross-linking in erythrocyte ghosts. The combined approach proved to be useful in understanding the mechanism by which these phenothiazine derivatives induce skin photosensitization. In particular, the photophysical properties of the compounds under investigation and the results of the study on their phototoxicity are in agreement with a mechanism that involves the radical cation of the drugs as a main intermediate.

In vitro studies of the phototoxic potential of the antidepressant drugs amitriptyline and imipramine.

Abstract: Amitriptyline and imipramine, two tricyclic antidepressant drugs, have been studied to evaluate their phototoxic potential using various models. Reactive oxygen species production was investigated. A negligible production of singlet oxygen was observed for both compounds whereas a significant production of superoxide anion was noted for amitriptyline in particular. Moderate red blood cell lysis under UVA light (365 nm) was induced in the presence of the two drugs at a concentration of 50 μM. Cellular phototoxicity was investigated on a murine fibroblast cell line (3T3). The two drugs were phototoxic causing cell death at a concentration of 100 μM and a UVA dose in the range of 3.3–6.6 J/cm 2 . Furthermore, the two drugs photosensitized the peroxidation of linoleic acid, as monitored by the formation of dienic hydroperoxides. The presence of BHA and GSH, two free radical scavengers, significantly reduced the lipid oxidation photoinduced by the drugs, suggesting a predominant involvement of radical species. Finally, the involvement of nucleic acids in the phototoxicity mechanism was also investigated using a pBR322 plasmid DNA as a model.

New Substructure Filters for Removal of Pan Assay Interference Compounds (PAINS) from Screening Libraries and for Their Exclusion in Bioassays

Abstract: This report describes a number of substructural features which can help to identify compounds that appear as frequent hitters (promiscuous compounds) in many biochemical high throughput screens. The compounds identified by such substructural features are not recognized by filters commonly used to identify reactive compounds. Even though these substructural features were identified using only one assay detection technology, such compounds have been reported to be active from many different assays. In fact, these compounds are increasingly prevalent in the literature as potential starting points for further exploration, whereas they may not be.

Bacterial topoisomerase inhibitors: quinolone and pyridone antibacterial agents.

Abstract: 3.1. Chelation 564 3.2. Acid−Base Character 564 3.3. Photochemistry 565 4. In Vitro Antimicrobial Spectra 566 5. Structure−Activity Relationships 568 5.1. N-1 Ethyl Family 568 5.2. N-1 Cyclopropyl Family 568 5.3. N-1 to C-8 Bridged (Tricyclic) Family 568 5.4. N-1 Aryl Family 569 5.5. Positions C-2, C-3, and C-4 570 5.6. C-4a Substituted Analogues 571 5.7. C-5 Substituents 571 5.8. C-6 Substituents 571 5.9. C-7 Substituents 571 5.9.1. Piperazinyl and Related Moieties 572 5.9.2. Pyrrolidinyl and Related Moieties 572 5.9.3. Cyclobutylaminyl and Related Moieties 572 5.9.4. Bicycloaminyl Moieties 572 5.9.5. Carbon-Linked Substituents 572 5.10. Substituents at C-8 573 5.11. Resume of Structure−Activity Relationships of Quinolones 573