Search results for "photochemotherapeutic"

Pyrano[2,3-e]isoindol-2-ones, new angelicin heteroanalogues

2009

A convenient synthesis of the pyrano[2,3-e]isoindol-2-one ring system, an heteroanalogue of angelicin, is reported. Our synthetic approach consists of the annelation of the pyran ring on the isoindole moiety using 5-dialkylamino- or 5-hydroxymethylene intermediates as building blocks. The photoantiproliferative activity of the new derivatives was studied. Some of them bearing the benzyl group at the 8 position were active with IC(50) in the micromolar range. Cell cytotoxicity involves apoptosis, alteration of cell cycle profile and membrane photodamage.

SYNTHESIS AND PHOTOCHEMIOTHERAPEUTIC ACTIVITY OF THIOPYRANO[2,3-E]INDOL-2-ONES

2004

A series of derivatives of the new ring system thiopyrano[2,3-e]indol-2-one was prepared with the aim of obtaining new photochemotherapeutic drugs. Biological screenings were performed on this new class of photoactivable drugs and a strong antiproliferative effect was observed upon irradiation with UVA light. The compound bearing a methyl substituent at the pyrrole nitrogen resulted as the most interesting showing IC50 in the nanomolar range.

THIOPYRANO[2,3-E]INDOL-2-ONES: ANGELICIN HETEROANALOGUES WITH POTENT PHOTOANTIPROLIFERATIVE ACTIVITY

2008

A new class of compounds, the thiopyrano[2,3-e]indol-2-ones, bioisosters of the angular furocoumarin angelicin, was synthesized with the aim of obtaining new photochemotherapeutic agents. In particular 7,8-dimethyl-thiopyranoindolone 6c s showed a remarkable phototoxicity and a great dose UVA dependence reaching IC(50) values at submicromolar level. This latter photoinduced a massive apoptosis and a remarkable photodamage to lipids and proteins. Although it did not intercalate DNA, it was able to cause photooxidation of DNA bases.

PHOTOCHEMOTHERAPEUTIC AGENTS: DESIGN, SYNTHESIS AND ANTITUMOR ACTIVITY

2009

Pyrrolo[3,2-h]quinazolines as Photochemotherapeutic Agents

2011

Heteroanalogues of angelicin, pyrrolo[3,2-h]quinazolines, were synthesized with the aim of obtaining new potent photochemotherapeutic agents. Many derivatives caused a significant decrease in cell proliferation in several human tumor cell lines after irradiation with UVA light (GI(50) =15.2-0.2 μM). Their phototoxicity effected apoptosis in Jurkat cells with the involvement of mitochondria (as determined by the loss of mitochondrial membrane potential and production of reactive oxygen species) and lysosomes. The phototoxicity of these compounds could be explained by lipid peroxidation.

Pyrrolo[3,4-h]quinolinones a new class of photochemotherapeutic agents

2011

Abstract Pyrrolo[3,4- h ]quinolin-2-ones were synthesized as nitrogen isosters of the angular furocoumarin angelicin, with the aim of obtaining new photochemotherapeutic agents with increased antiproliferative activity and lower undesired toxic effects. A versatile synthetic pathway was approached to allow the isolation of derivatives of the new ring system with a good substitution pattern on the pyrrole moiety. Photobiological screenings of the new compounds revealed a potent phototoxic effect and a great UVA dose dependence, reaching IC 50 values at submicromolar level. The induced cellular photocytotoxicity was related to apoptosis with the involvement of mitochondria and lysosomes, alte…

Photochemotherapeutic haterocyclic agents having antiproliferative and antineoplastic activity

2011

Photochemotherapeutic heterocyclic agents having antiproliferative and antineoplastic activity

2012

The present invention concerns the synthesis of new analogs of angelicins, pyrrolo[3,2-h]quinoline, for the treatment of pathologie having hyperproliferative character including those having neoplastic nature. The treatment is based on the combined action of pyrrolo[3,2-h]quinolines and UV-A light, through a clinical approach defined as PUVA (psoralen-UVA light). The most important feature of these compounds is that they exert their remarkable phototoxicity without any DNA damage, which is the main origin of the side effects of the PUVA therapy