Antonio Botta

Synthesis and biological evaluation of new N-alkylcarbazole derivatives as STAT3 inhibitors: preliminary study.

The signalling pathway of Janus tyrosine Kinases-Signal Transducers and Activators of Transcription (JAK-STAT) is activated by a number of cytokines, hormones (GH, erythropoietin and prolactin), and growth factors. JAK-STAT signalling is involved in regulation of cell proliferation, differentiation and apoptosis. These activities are due to different members of JAK-STAT family consisting of: JAK1, JAK2, JAK3, Tyk2 and STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, STAT6. Recent studies suggest a key role for STAT family proteins, in particular for STAT3, in selectively inducing and maintaining a pro-carcinogenic inflammatory microenvironment, that promote tumour cells transformation. Moreover, a striking correlation between cancer development/progression and STAT3 persistent activation exists, probably due to STAT3 promoting of the pro-oncogenic inflammatory pathways, like NF-kB, IL-6 and JAK family kinases. Recent study demonstrated that carbazoles can inhibit STAT3 mediated transcription. From these evidences, STAT3 represents a therapeutic target, so we have synthesized a new set of N-alkylcarbazole derivatives substituted in positions 2, 4 and 6, to evaluate their activity on STAT3. Some of these compounds showed an interesting activity as STAT3 selective inhibitors; in particular, compounds 9a 9b and 9c revealed to inhibit the STAT3 activation for the 50%, 90% and 95%, respectively.

Synthesis, characterization and cytotoxic activity on breast cancer cells of new half-titanocene derivatives.

A series of novel titanocene-complexes has been prepared and evaluated for their growth regulatory effects in MCF7 and SkBr3 breast cancer cells. The capability of some of these compound to elicit relevant repressive effects on cancer cell growth could be taken into account towards novel pharmacological approaches in cancer therapy.

New titanocene derivatives with high antiproliferative activity against breast cancer cells

The synthesis and characterization of some new titanocene-complexes, having a ethenyl-phenoxide or a benzyl group as substituents of the cyclopentadienyl rings, are reported. The synthesized compounds have been evaluated for their cytotoxic potential against two human breast cancer cell lines, that is: MCF7 and SkBr3. Most of these compounds have shown significant cytotoxic effects, compared to cisplatin, in MTT-based cell tests.

Different 6-Aryl-Fulvenes Exert Anti-proliferative effects on Cancer Cells

Fulvenes represent a class of molecules very interesting under a chemical point of view because are easily accessible starting materials and are still poorly characterized for their biological activities, with the exception of acylfulvene and irofulvenes which have been reported to exert cytotoxic properties. Here, we describe the synthesis and characterization of several aryl-fulvenes together with their effects on cancer cell growth by MTT method. The cytotoxic potential was investigated on a panel of tumor cell lines such as breast MCF7 and SkBr3, endometrial Ishikawa, prostate LnCaP and lung A549, in comparison with the cis-diamminedichloroplatinum(II) (cisplatin) which is largely used for the treatment of different types of cancer. The evaluation of the cytotoxic activity of these compounds indicated that they are able to inhibit the proliferation of the aforementioned cancer cell types. In particular, the compound 4 exhibited the most powerful antiproliferative activity on all tumor cells evaluated with higher inhibitory effects respect to cisplatin and without altering the proliferation of human mammary MCF-10A epithelial cells.

Identification of Lead Compounds as Inhibitors of STAT3: Design, Synthesis and Bioactivity

STAT3 belongs to the signal transducers and activators of transcription (STAT) family. It has been demonstrated that STAT3 is constitutively activated in many tumors, playing a role in carcinogenesis and tumor progression. For this reason, it has being considered a potential target for cancer therapy. In this context, we have designed, synthesized and evaluated 1,4‐dimethyl‐carbazole derivatives, targeting the STAT3 protein. Moreover, MTT assay performed on A375 and HeLa, showed significant antiproliferative activity of some of synthesized compounds (3–5). The same compounds (3–5) considerably reduced STAT3 expression, as demonstrated by Western blot analysis. Our multidisciplinary approach shows that 1,4‐dimethyl‐carbazoles are potential building blocks to develop more affinity ligands of STAT3.

Highly Isotactic Poly(N-butenyl-carbazole): Synthesis, Characterization, and Optical Properties

The synthesis of isotactic poly(N-butenyl-carbazole) (-PBK) by using homogeneous isospecific Ziegler-Natta catalytic system is reported. The achieved polymer is crystalline and shows, to DSC and X-ray analysis, two distinct crystalline phases. -PBK FTIR spectrum and X-ray diffraction pattern are compared with those of poly(N-vinylcarbazole) (PVK). The observed differences are tentatively associated with higher flexibility of the -PBK chains due to the alkylene group connecting the carbazole group to the main chain. -PBK optical properties are also compared with those of PVK and isotactic poly(N-pentenyl-carbazole) (-PPK), a higher homologue of -PBK recently used as emitting layer in organic light emitting diodes (OLEDs) showing white light emission. The close similarity of the fluorescence spectra of -PBK and -PPK is a promising basis for optical applications of this polymer.

Highly isotactic poly(N-pentenyl-carbazole): A challenging polymer for optoelectronic applications

The synthesis and the microstructural, morphological, optical characterization of poly (N-pentenyl-carbazole) are reported. The obtained polymer present a stereoregular isotactic microstructure and is cristalline with a Tm of 138°C. Photoluminescence analysis of chlorobenzene polymer films, having high homogeneity and low roughness, show that PPK emits in a broad spectrum range 350-600 nm.

Blue and white OLEDs with highly stereoregular polymers

Organic light emitting diodes (OLEDs) are fabricated using two novel polymers, isotactic and syndiotactic poly(N-pentenyl-carbazole) (i-PPK and s-PPK), as emitting layers. The electroluminescence spectra of the devices are analyzed in comparison with the photoluminescence spectra of polymer films and are related to their microstructure properties. Blue light emitting diodes are obtained, except for the i-PPK based multilayer OLED, which emits white light due to three contributions (electroplex fluorescence, excimer phosphorescence and electromer emission). The results show that the polymer tacticity strongly affects the photoconductive properties of the devices.