569-54-0Relevant articles and documents
Highly Effective Dual-Function Near-Infrared (NIR) Photosensitizer for Fluorescence Imaging and Photodynamic Therapy (PDT) of Cancer
Patel, Nayan,Pera, Paula,Joshi, Penny,Dukh, Mykhaylo,Tabaczynski, Walter A.,Siters, Kevin E.,Kryman, Mark,Cheruku, Ravindra R.,Durrani, Farukh,Missert, Joseph R.,Watson, Ramona,Ohulchanskyy, Tymish Y.,Tracy, Erin C.,Baumann, Heinz,Pandey, Ravindra K.
, p. 9774 - 9787 (2016)
We report herein the synthesis and biological efficacy of near-infrared (NIR), bacteriochlorin analogues: 3-(1′-butyloxy)ethyl-3-deacetyl-bacteriopurpurin-18-N-butylimide methyl ester (3) and the corresponding carboxylic acid 10. In in vitro assays, compared to its methyl ester analogue 3, the corresponding carboxylic acid derivative 10 showed higher photosensitizing efficacy. However, due to drastically different pharmacokinetics in vivo, the PS 3 (HPLC purity >99%) showed higher tumor uptake and long-term tumor cure than 10 (HPLC purity >96.5%) in BALB/c mice bearing Colon 26 tumors. Isomerically pure R- and S- isomers of 3 (3a and 3b, purity by HPLC > 99%) under similar treatment parameters showed identical efficacy in vitro and in vivo. In addition, photosensitizer (PS) 3 showed limited skin phototoxicity and provides an additional advantage over the clinically approved chemically complex hematoporphyrin derivative as well as other porphyrin-based PDT agents, which makes 3 a promising dual-function agent for fluorescence-guided surgery with an option of phototherapy of cancer.
Synthesis, spectroscopic, and in vitro photosensitizing efficacy of ketobacteriochlorins derived from ring-B and ring-D reduced chlorins via pinacol-pinacolone rearrangement
Joshi, Penny,Ethirajan, Manivannan,Goswami, Lalit N.,Srivatsan, Avinash,Missert, Joseph R.,Pandey, Ravindra K.
, p. 8629 - 8640 (2011)
In this report, we present a regioselective oxidation of a series bacteriochlorins, which on reacting with either ferric chloride (FeCl 3) or 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) yielded the corresponding ring-B or ring-D reduced chlorins. The effect of the number of electron-withdrawing groups present at the peripheral position, with or without a fused isocyclic ring (ring-E), did not make any significant difference in regioselective oxidation of the pyrrole rings. However, depending on the nature of substituents, the intermediate bis-dihydroxy bacteriochlorins on subjecting to pinacol-pinacolone reaction conditions gave various ketochlorins. The introduction of the keto-group at a particular position in the molecule possibly depends on the stability of the intermediate carbocation species. The newly synthesized bacteriochlorins show strong long-wavelength absorption and produced significant in vitro (Colon26 cells) photosensitizing ability. Among the compounds tested, the bacteriochlorins containing a keto-group at position 7 of ring-B with cleaved five-member isocyclic ring showed the best efficacy.
Studies on the biosynthesis of corrinoids and porphyrinoids. X. Biosynthetic studies of bacteriochlorophyll-a in Rhodopseudomonas spheroides: Incorporation of 2H-, 13C- and 15N-labeled substrates and origin of the hydrogen atoms
Okazaki,Kajiwara
, p. 1311 - 1317 (1995)
The biosynthetic pathway of bacteriochlorophyll-a in Rhodopseudomonas spheroides was investigated by administration of [2-13C]glycine, L-[methyl- 13C]methionine, L-[1-13C]glutamic acid and 13C- or 15N-labeled δ- aminolevulinic acid (ALA). The origin of the hydrogen atoms was studied by following the incorporation into bacteriochlorophyll of 13C-labeled ALA in a medium containing 50% D2O and that of 2H-, 13C-labeled ALA. The labeled bacteriochlorophylls were converted into more stable methyl bacteriopheophorbides, which were subjected to 13C-NMR analyses to obtain information about the biosynthetic origin of the hydrogen atoms. The use of 13C-enriched bacteriochlorophylls and methyl bacteriopheophorbides allowed us to make 13C-NMR signal assignments for all carbons of the porphyrin nucleus.
Modulation of reactive oxygen species photogeneration of bacteriopheophorbide a derivatives by exocyclic E-ring opening and charge modifications
Roxin, áron,Chen, Juan,Paton, Andrew S.,Bender, Timothy P.,Zheng, Gang
, p. 223 - 237 (2014/02/14)
With the knowledge that the dominant photodynamic therapy (PDT) mechanism of 1a (WST09) switched from type 2 to type 1 for 1b (WST11) upon taurine-driven E-ring opening, we hypothesized that taurine-driven E-ring opening of bacteriochlorophyll derivatives and net-charge variations would modulate reactive oxygen species (ROS) photogeneration. Eight bacteriochlorophyll a derivatives were synthesized with varying charges that either contained the E ring (2a-5a) or were synthesized by taurine-driven E-ring opening (2b-5b). Time-dependent density functional theory (TDDFT) modeling showed that all derivatives would be type 2 PDT-active, and ROS-activated fluorescent probes were used to investigate the photogeneration of a combination of type 1 and type 2 PDT ROS in organic- and aqueous-based solutions. These investigations validated our predictive modeling calculations and showed that taurine-driven E-ring opening and increasing negative charge generally enhanced ROS photogeneration in aqueous solutions. We propose that these structure-activity relationships may provide simple strategies for designing bacteriochlorins that efficiently generate ROS upon photoirradiation.
LIPOPROTEIN NANOPLATFORMS
-
Page/Page column 63, (2008/06/13)
The present invention provides a non-naturally occurring lipoprotein nanoplatform ("LBNP") comprising at least one cell surface receptor ligand; at least one lipoprotein; and at least one diagnostic agent and/or at least one therapeutic agent. In embodime
