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Keywords = aryloxazole derivative

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7 pages, 1961 KiB  
Communication
Synthesis of Bisoxazole and Bromo-substituted Aryloxazoles
by Sambasivarao Kotha and Subba Rao Cheekatla
Molbank 2022, 2022(3), M1440; https://doi.org/10.3390/M1440 - 6 Sep 2022
Cited by 2 | Viewed by 2829
Abstract
Herein, we report a bisoxazole derivative as well as a bromo-substituted oxazole derivatives via a simple approach. The synthesis begins with an inexpensive and readily available starting material, such as 2,5-dimethoxybenzaldehyde, hydroquinone, and p-toluenesulfonylmethyl isocyanide (TosMIC). This approach relies on the Van [...] Read more.
Herein, we report a bisoxazole derivative as well as a bromo-substituted oxazole derivatives via a simple approach. The synthesis begins with an inexpensive and readily available starting material, such as 2,5-dimethoxybenzaldehyde, hydroquinone, and p-toluenesulfonylmethyl isocyanide (TosMIC). This approach relies on the Van Leusen oxazole method and electrophilic aromatic bromination. The structures of bisoxazole and bromosubstituted aryloxazoles were fully supported by spectroscopic methods (IR, NMR, and HRMS) and further established using single crystal X-ray diffraction studies. Full article
(This article belongs to the Section Organic Synthesis and Biosynthesis)
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14 pages, 3038 KiB  
Article
Development of an Aryloxazole Derivative as a Brain-Permeable Anti-Glioblastoma Agent
by Seulgi Shin, Sungsu Lim, Ji Yeon Song, Dohee Kim, Min Jeong Choi, Changdev G. Gadhe, A Young Park, Ae Nim Pae and Yun Kyung Kim
Pharmaceutics 2019, 11(10), 497; https://doi.org/10.3390/pharmaceutics11100497 - 28 Sep 2019
Cited by 2 | Viewed by 3766
Abstract
Glioblastoma drug development has been difficult due to the extremely low blood brain barrier (BBB) penetration of conventional anti-cancer agents. P-glycoprotein, an efflux membrane transporter, is responsible for the poor brain uptake of small and hydrophobic drug substances. To develop brain-penetrable anti-tumor agents, [...] Read more.
Glioblastoma drug development has been difficult due to the extremely low blood brain barrier (BBB) penetration of conventional anti-cancer agents. P-glycoprotein, an efflux membrane transporter, is responsible for the poor brain uptake of small and hydrophobic drug substances. To develop brain-penetrable anti-tumor agents, we designed colchicine derivatives containing an aryloxazole moiety, which is known to inhibit P-glycoprotein. Among those tested, an aryloxazole derivative named KIST-G1 showed the strongest anti-glioblastoma cell proliferation activity (IC50 = 3.2 ± 0.8 nM). Compared to colchicine, KIST-G1 showed dramatically increased BBB-permeable properties presenting 51.7 ± 0.5 (10−6 cm/s) parallel artificial membrane permeability assay (PAMPA) permeability and 45.0 ± 6.0% of P-gp inhibition. Aid by the BBB-permeable properties, KIST-G1 (5 mg/kg) suppressed glioblastoma cell growth and migration almost completely in the brain of glioblastoma xenograft models by showing 98.2 ± 0.1% reduced tumor area compared with phosphate buffered saline (PBS)-injected control. In comparison, temozolomide, which is the most widely used drug for glioblastoma, showed only moderate effects. Our results demonstrate the effectiveness of an aryloxazole moiety in targeting brain tumors and suggest KIST-G1 as a potent anti-glioblastoma agent. Full article
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