Primary screening of substances-photosensibilizers of the bacteriochlorin range for photodynamic therapy of malignant neoplasms

Autor: I. V. Pantushenko, P.V. Ostroverkhov, E. A. Plotnikova, A. D. Kaprin, Raisa I. Yakubovskaya, M. A. Grin
Rok vydání: 2018
Předmět:
Zdroj: Biomeditsinskaya Khimiya. 64:283-289
ISSN: 2310-6905
2310-6972
DOI: 10.18097/pbmc20186403283
Popis: This paper presents a primary screening of bacteriochlorin-type compounds with aminoamide, propyl and carbohydrate substituents aimed for development a new generation photosensitizers (PS) for photodynamic therapy of malignant tumors. Absorption and fluorescence spectral characteristics of the compounds, their storage stability in solutions under dark conditions and light exposure, photo-induced and dark cytotoxicity against human HEp2 tumor cells have been studied. It has been shown that the dyes with aminoamide substituents have an absorbtion maximum at 754±2 nm in the long wavelength region and they are not stable during storage (the specific fluorescence intensity decreased by 33-56% during 24 hours). The long wavelength region absorption of the propyl and carbohydrate substituted compounds varied in the range 780-831 nm, they were stable in solutions during storage and under light irradiation. Except the dye with a carbohydrate residue in the exocycle E, all PS exhibited the high photo-induced activity and low level of the dark cytotoxicity. The highest photo-induced cytotoxicity was observed for compounds with aminoamide substituents inthe macrocyclic ring (IC 50 values ranged from 17 nM to49 nM after 2 hour incubation with PS followed by exposure to the 10 J/cm 2 dose of red light). Taking into account the totality of the physico-chemical and biological properties, as well as manufacturability of production, O-propyloxime-N-propoxybacteriopurinimide methyl ester was chosen as the most promising candidate compound for further investigations.Proveden pervichnyĭ skrining substantsiĭ-fotosensibilizatorov (FS) bakteriokhlorinovogo riada s aminoamidnymi, propil'nym i uglevodnymi zamestiteliami; on vkliuchal otsenku spektral'nykh kharakteristik dannykh soedineniĭ, ikh ustoĭchivost' pri khranenii v rastvore v zatemnennykh usloviiakh i pri svetovom vozdeĭstvii, a takzhe izuchenie fotoindutsirovannoĭ aktivnosti i tsitotoksichnosti na opukholevykh kletkakh NEr2. Po rezul'tatam absorbtsionnogo i fluorestsentnogo analizov krasiteli s aminoamidnymi zamestiteliami imeiut maksimum pri 754±2 nm, ne stabil'ny pri khranenii (v techenie sutok otmechali snizhenie intensivnosti fluorestsentsii na 33-56%); soedineniia s propil'nym i uglevodnymi zamestiteliami pogloshchaiut v oblasti 780-831 nm i kharakterizuiutsia stabil'nost'iu pri khranenii i obluchenii. Vse FS, krome krasitelia s uglevodnym ostatkom v ékzotsikle E, obladaiut fotoindutsirovannoĭ aktivnost'iu pri otsutstvii temnovoĭ toksichnosti. Naibolee vysokaia fotoaktivnost' zaregistrirovana u soedineniĭ s aminoamidnymi fragmentami v makrotsiklicheskom kol'tse (pri 2-kh chasovoĭ inkubatsii IC 50 sostavliala ot 17 nM do 49 nM). Uchityvaia sovokupnost' fiziko-khimicheskikh i biologicheskikh svoĭstv, a takzhe tekhnologichnost' polucheniia i stabil'nost' pri khranenii i obluchenii, dlia dal'neĭshikh issledovaniĭ s tsel'iu sozdaniia fotosensibilizatora novogo pokoleniia dlia fotodinamicheskoĭ terapii zlokachestvennykh novoobrazovaniĭ vybran metilovyĭ éfir O-propiloksim-N-propoksibakteriopurpurinimida.
Databáze: OpenAIRE
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