Pursuing Polypharmacology: Benzothiopyranoindoles as G-Quadruplex Stabilizers and Topoisomerase I Inhibitors for Effective Anticancer Strategies.

Here, we explored the benzothiopyranoindole scaffold to develop antiproliferative agents with a polypharmacological profile targeting both G-quadruplex (G4)-structures and Topoisomerase (Topo) I enzyme. In a preliminary optimization phase, compound was selected from an in-house collection as a suitable lead for the rational development of a small library of analogs (-). When assayed in NIH's NCI-60 Human Cancer Cell Line In Vitro Screen Program, compound and its demethylated analogue showed significant antiproliferative/cytotoxic activity.

Cost-Effectiveness Analysis of Topical Treatments for Actinic Keratosis in Italian National Health System.

Actinic keratosis (AK) is a widespread pre-cancerous skin condition that may evolve to squamous cell carcinoma, a non-melanoma skin cancer, which is able to become locally invasive and metastatic. Thus, it is important to treat AK. : We conducted a cost-effectiveness analysis for the field-directed therapeutic approaches: local application of drugs containing 5-fluorouracil, both alone at a 4% concentration and associated to 10% salicylic acid at a 0.

Systemic Photoprotection in Melanoma and Non-Melanoma Skin Cancer.

Non-melanoma skin cancers (NMSCs), which include basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and actinic keratosis (AK), are the most common cancer diseases in the Caucasian race. If diagnosed late and improperly treated, BCC and SCC can become locally advanced and metastasize. Malignant melanoma (MM) is less frequent but more lethal than NMSC.

Cannabidiol as Self-Assembly Inducer for Anticancer Drug-Based Nanoparticles.

Cannabidiol (CBD) is a biologically active compound present in the plants of the family, used as anticonvulsant, anti-inflammatory, anti-anxiety, and more recently, anticancer drug. In this work, its use as a new self-assembly inducer in the formation of nanoparticles is validated. The target conjugates are characterized by the presence of different anticancer drugs (namely -desacetyl thiocolchicine, podophyllotoxin, and paclitaxel) connected to CBD through a linker able to improve drug release.

-Dichloro(triphenylarsino)(,-dialkylamino)platinum(II) Complexes: In Search of New Scaffolds to Circumvent Cisplatin Resistance.

The high incidence of the resistance phenomenon represents one of the most important limitations to the clinical usefulness of cisplatin as an anticancer drug. Notwithstanding the considerable efforts to solve this problem, the circumvention of cisplatin resistance remains a challenge in the treatment of cancer. In this work, the synthesis and characterization of two -dichloro(triphenylarsino)(,-dialkylamino)platinum(II) complexes ( and ) were described.

New Platinum(II) Complexes Affecting Different Biomolecular Targets in Resistant Ovarian Carcinoma Cells.

Resistance to platinum-based anticancer drugs represents an important limit for their clinical effectiveness and one of the most important field of investigation in the context of platinum compounds. From our previous studies, Pt complexes containing the triphenylphosphino moiety have been emerging as promising agents, showing significant cytotoxicity to resistant ovarian carcinoma cells. Two brominated triphenylphosphino trans-platinum derivatives were prepared and evaluated on human tumor cell lines, sensitive and resistant to cisplatin.

Systemic Photoprotection in Skin Cancer Prevention: Knowledge among Dermatologists.

Background: Systemic photoprotection (i.e., administration of substances such as nicotinamide, carotenoids, and vitamin D) may be important to reduce photocarcinogenesis or to support long-term protection against UV irradiation.

Cytotoxicity and DNA interaction in a series of aryl terminated iminopyridine Pt(II) complexes.

A series of iminopyridine complexes of platinum(II), bearing a flexible diethereal, aryl terminated residue, where the size of aryl group is varied from phenyl to 9-anthracenyl, was synthesized. The new complexes are soluble and stable in DMSO/HO mixtures. Besides the metal center, aryl groups are available for further interactions with DNA, due to the good side chain flexibility.

Platinum(II) Complexes Bearing Triphenylphosphine and Chelating Oximes: Antiproliferative Effect and Biological Profile in Resistant Cells.

Platinum(II) complexes of the type [Pt(Cl)(PPh ){(κ -N,O)-(1{C(R)=N(OH)-2(O)C H })}] with R=Me, H, (1 and 2) were synthesized and characterized. Single-crystal X-ray diffraction confirmed the proposed (SP4-3) configuration for 1. Study of the antiproliferative activity, performed on a panel of human tumor cell lines and on mesothelial cells, highlighted complex 2 as the more effective.

New Class of Betulinic Acid-Based Nanoassemblies of Cabazitaxel, Podophyllotoxin, and Thiocolchicine.

Betulinic acid is validated as a new self-assembly inducer for the formation of nanoparticles (NPs) in combination with different drugs. The target compounds are characterized by the presence of anticancer drugs acting on tubulin dynamics and of a linker that could be a carbon chain or a triazole-based one. Nanoparticles formed are characterized and their biological activity is evaluated.

Synthesis, Antiproliferative Effect, and Topoisomerase II Inhibitory Activity of 3-Methyl-2-phenyl-1-indoles.

A series of 3-methyl-2-phenyl-1-indoles was prepared and investigated for antiproliferative activity on three human tumor cell lines, HeLa, A2780, and MSTO-211H, and some structure-activity relationships were drawn up. The GI values of the most potent compounds ( and ) were lower than 5 μM in all tested cell lines. For the most biologically relevant derivatives, the effect on human DNA topoisomerase II relaxation activity was investigated, which highlighted the good correlation between the antiproliferative effect and topoisomerase II inhibition.

DNA interaction of a fluorescent, cytotoxic pyridinimino platinum(II) complex.

New pyridinimino complexes of platinum(II) [PtCl(N^N-R)] (N^N = 2-pyridylmethanimino, R = -(CH)O(CH)OH, -(CH)O(CH)OCHPyr), Pyr = pyren-1-yl) have been prepared. They are characterized by a dioxygenated alkyl side chain and, in one case, by a fluorescent terminal 1-pyrenyl residue. The complexes were characterized by elemental analysis, IR, H-, C-and Pt NMR spectroscopies.

Benzothiopyranoindole- and pyridothiopyranoindole-based antiproliferative agents targeting topoisomerases.

New benzothiopyranoindoles (5a-l) and pyridothiopyranoindoles (5m-t), featuring different combinations of substituents (H, Cl, OCH) at R-R positions and protonatable R-dialkylaminoalkyl chains, were synthesized and biologically assayed on three human tumor cell lines, showing significant antiproliferative activity (GI values spanning from 0.31 to 6.93 μM) and pro-apoptotic effect.

Exploring the Biological Activity of a Library of 1,2,5-Oxadiazole Derivatives Endowed With Antiproliferative Activity.

Background/aim: The identification of a series of oxadiazole-based compounds, as promising antiproliferative agents, has been previously reported. The aim of this study was to explore the SAR of newly-synthesized oxadiazole derivatives and identify their molecular targets.

Materials And Methods: A small library of 1,2,5-oxadiazole derivatives was synthetized and their antiproliferative activity was tested by the MTT assay.

Heteronanoparticles by Self-Assembly of Ecdysteroid and Doxorubicin Conjugates To Overcome Cancer Resistance.

Heteronanoparticles (H-NPs) consisting of conjugates characterized by a squalene tail linked to doxorubicin and ecdysteroid derivatives are presented. Biological evaluation on A2780ADR cell line confirms not only the maintenance of the activity of the parental drug but also the ability to overcome cancer resistance. The cell uptake was demonstrated, and the involvement of an endosomal-mediated pathway was suggested.