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Synthesis and Evaluation of a CBZ-AAN-Dox Prodrug and its in vitro Effects on SiHa Cervical Cancer Cells Under Hypoxic Conditions


, : Synthesis and Evaluation of a CBZ-AAN-Dox Prodrug and its in vitro Effects on SiHa Cervical Cancer Cells Under Hypoxic Conditions. Chemical Biology & Drug Design 86(4): 589-598

Although doxorubicin (Dox) is widely used in clinical treatment for solid tumors, it causes many side-effects such as heart and kidney damage, bone marrow suppression, and drug resistance. Legumain is a lysosomal protease that is elevated and associated with an invasive and metastatic phenotype in a number of solid tumors. In this study, we designed and synthesized a Dox prodrug, N-benzyloxycarbonyl-Ala-Ala-Asn-Doxorubicin (CBZ-AAN-Dox), with 94% purity. Single substrate kinetic assays demonstrated hLegumain-specific enzymatic cleavage and activation of the prodrug in vitro, and this enzymatic cleavage of the prodrug substrate was more sensitive in acidic conditions, releasing more than 70% of Dox after 24 h. Treatment of tumor cells with our prodrug demonstrated a much higher IC50 value, significantly enhanced uptake of the prodrug, and considerably less cellular toxicity compared to Dox treatment alone. Our study presents a novel prodrug, CBZ-AAN-Dox, to potentially increase both the safety and efficacy of clinical treatment of tumors by exploiting the tumor's innate expression of legumain.

US$19.90

PMID: 25619622

DOI: 10.1111/cbdd.12525


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Chan, M.Yin.; Komatsu, K.; Li, S-Lin.; Xu, Y.; Darmawan, P.; Kuramochi, H.; Nakaharai, S.; Aparecido-Ferreira, A.; Watanabe, K.; Taniguchi, T.; Tsukagoshi, K., 2013: Suppression of thermally activated carrier transport in atomically thin MoS2 on crystalline hexagonal boron nitride substrates. We present the temperature-dependent carrier mobility of atomically thin MoS2 field-effect transistors on crystalline hexagonal boron nitride (h-BN) and SiO2 substrates. Our results reveal distinct weak temperature dependence of the MoS2 devices o...

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Wang, W.-Li-; Yeh, S.-Farn-; Huang, E.-Yi-Kung-; Lu, Y.-Ling-; Wang, C.-Fa-; Huang, C.-Ying, F.; Lin, W.-Jinq, 2007: Mitochondrial anchoring of PKCl by PICK1 confers resistance to etoposide-induced apoptosis. Various pathways, including regulation of functions of the Bcl-2 family, are implicated in the survival promotion by PKCl, however the molecular mechanisms are still obscure. We have previously demonstrated that PKCl is selectively anchored to mit...

Ferrando, J.; Corretger, J.M.; Seres, A., 1997: Cutaneous manifestation of children of Fundacio Catalana Sindrome de Down of Barcelona. Cytogenetics & Cell Genetics 77(SUPPL 1): 22

Keya, N.C.O.; Eijnatten, C.L.M. van, 1975: Studies on oversowing of natural grasslands. 3. The seeding rates for the establishment of Desmodium uncinatum (Jacq.) DC when oversown or sod-seeded in Hyparrhenia grassland. In a trial in 1972-3, D. uncinatum was oversown or sod-sown into Hyparrhenia spp. grassland at 8 sowing rates ranging from 1 to 15 kg seed/ha. Sod-sowing gave better seedling establishment and higher DM yields up to 14 months after sowing than ove...

Yan, L.; Harper, J.; Louis, G.; Fang, J.; Moses, M.A., 2002: A zinc finger protein differentially expressed during the angiogenic switch Regulation by hypoxia and modulation of VEGF expression. Proceedings of the American Association for Cancer Research Annual Meeting 43: 29-30, March

Kunc K., 1966: Clitocybe nebularis. Mykologicky Sbornik 43(5-6): 81

Benedict, Lauryn, 2008: Occurrence and life history correlates of vocal duetting in North American passerines. Vocal duetting, where two birds produce temporally coordinated vocalizations, has been reported in a taxonomically and geographically diverse set of avian species. Researchers have suggested a number of potential correlates of duetting, including...

Legkonogov, A.V.; Kutsenko, A.I.; Zaruba, A.Iu.; Arabidze, G.G.; Kukharchuk, V.V., 1988: Use of plasmapheresis in the treatment of patients with severe arterial hypertension refractory to drug therapy. Thirty patients with severe and malignant arterial hypertension (AH) received 1-4 sessions (in most cases 2) of plasmapheresis to overcome refractiveness to drug therapy. Stable BP reduction, improvement of the vascular picture of the fundus of th...

Meurs, A. van; Cohen, A.; Edelbroek, P., 1992: Atropine poisoning after eating chapattis contaminated with Datura stramonium (thorn apple). The case histories of 7 patients in Tanzania with typical atropine poisoning are described. All had eaten chapattis made from flour contaminated with D. stramonium.