Advances in copper complexes as anticancer agents.

Whereas the photodynamic therapy (PDT) of cancer has recently shown rapid clinical acceptance, photodynamic antimicrobial chemotherapy (PACT)--which predates the related cancer regimen--is not widely appreciated. Like PDT, PACT utilizes photosensitizers and visible or ultraviolet light in order to give a phototoxic response, normally via oxidative damage. Currently, the major use of PACT is in the disinfection of blood products, particularly for viral inactivation, although more clinically-based protocols are being developed, e.g. in the treatment of oral infection. The technique has been shown to be effective in vitro against bacteria (including drug-resistant strains), yeasts, viruses and parasites. A wide range of photosensitizers, both natural and synthetic, is available with differing physicochemical make-up and light-absorption properties. PACT is proposed as a potential, low-cost approach to the treatment of locally occurring infection.

/pdf/photodynamic-antimicrobial-chemotherapy-pact-fjpybi4xr9.pdf

Photodynamic antimicrobial chemotherapy (PACT).

Isolation and synthesis of biologically active carbazole alkaloids

https://science.sciencemag.org/content/sci/162/3857/963.full.pdf

Mechanisms of Photosensitized Oxidation

— The photochemistry and photobiology of psoralens have been rcvicwed on the basis of selected literature. In addition to the well establishcd photoaddition of psoralens to DNA. photoreac-tions involving RNA. tRNA and proteins warrant further studies. Although thymine seems to be one of the predominant bases for the psoralen photocycloaddition in DNA. photoreactions of other bases such as adenine and the mechanisms other than cycloaddition should also be investigated in order to fully assess the specificity of psoralen photoreactions and their application BS a probe for biopolymer structure and as a tool for photobiological studies of microorganisms. The relativc photobiological importance of monoaddition vs crosslinking of psoralens to nucleic acids also remains to be fully elucidated.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1751-1097.1979.tb07838.x

Photochemistry and photobiology of psoralens.

After irradiation at 3655 A of an aqueous frozen solution containing thymine and psoralen, a new photocompound was isolated by column chromatography. It contains a furocoumarin and a pyrimidine-moiety linked together by the formation of a cyclobutane ring (see formulas II and III). By irradiation at 2537 A in acetic acid solution, the photocompound breaks up again yielding psoralen and thymine. From an aqueous frozen solution containing cytosine and psoralen irradiated at 3655 A, an analogous photocompound was obtained, which, however, consists of the addition to psoralen of a uracil molecule, instead of a cytosine one (IV, V). It has been stated that the hydrolytic deamination of the cytosine moiety to the uracil one takes place during the working up of the photocompound in aqueous solution after irradiation. Substances with properties similar to those above were obtained from bergapten (5-methoxy-psoralen) and thymine, from psoralen and thymidine or thymidylic acid, irradiated at 3655 A.



The new substances may be considered as model compounds in explaining the photoreactions which take place between the skin-photosensitizing furocoumarins and DNA upon irradiation at 3655 A.

Photoreactions at 3655 Angstrom between pyrimidine bases and skin-photosensitizing furocoumarins.

Photoreactions at 3655 å linking the 3–4 double bond of furocoumarins with pyrimidine bases

The possible presence of methylpsoralens as undesired inquinants in synthetic methylangelicins has been avoided through a synthetic pathway starting from umbelliferones carrying a methyl group in the 6-position The new 6-methylangelicins show a high affinity toward DNA, forming in the dark a molecular complex; the complexed angelicins under UV-A irradiation photobind effectively to the macromolecule, forming only monoadducts The new compounds show an evident antiproliferative activity by inhibiting DNA synthesis on Ehrlich cells; great differences, however, can be seen between the various compounds All the compounds are lacking of skin erythemogenic activity Some of the new 6-methylangelicins, evaluated in terms of mutagenic activity, demonstrate to be less effective than 8-methoxypsoralen (8-MOP), used for a comparison On the basis of antiproliferative activity, lack of skin phototoxicity, and low mutagenicity, two compounds have been chosen for clinical evaluation The compounds tested on seven psoriatic patients by topical application and UV-A irradiation proved to be more effective than 8-MOP, used in the same conditions

Franco Bordin

Papers

Photoreactions at 3655 Angstrom between pyrimidine bases and skin-photosensitizing furocoumarins.

Photoreactions at 3655 å linking the 3–4 double bond of furocoumarins with pyrimidine bases

6-Methylangelicins: a new series of potential photochemotherapeutic agents for the treatment of psoriasis.

Angelicins, angular analogs of psoralens: chemistry, photochemical, photobiological and phototherapeutic properties.

Pt(II) and Pd(II) derivatives of ter-butylsarcosinedithiocarbamate. Synthesis, chemical and biological characterization and in vitro nephrotoxicity.