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Blood–Brain Barrier Permeability of Methyl-3,4-dihydroxybenzoate derivative NO.2 for Neurodegenerative Diseases Treatment

Weiyi Liu, Jitao Hai, Yan Luo, Huanmin Luo

Abstract


Background The blood-brain barrier (BBB) plays a crucial role in the central nervous system (CNS) homeostasis maintenance. However, BBB limits drug entrance into the brain, leading to reduced bioavailability in the CNS. Preliminarily, a BBB in vitro model can help detect drug permeability and simplify the operation and reduce the initial cost of drug development. A methyl-3,4-dihydroxybenzoate (MDHB) derivative, 4-(1-(3,4-dihydroxyphenyl)-1H-1,2,3-triazol-4-yl) benzoic acid (NO.2), synthesized in our lab in previous studies, presents a neurotrophic effect and is more effective than lead derivatives. However, its BBB permeability remains unknown.

Methods We used Madin-Darby Canine Kidney (MDCK) cells to establish a BBB in vitro model to detect if NO.2 could penetrate the BBB.

Results The results showed that the NO.2 apparent permeability (Papp) was greater than 0.1×10-6 cm·s-1. Therefore, it was characterized as a moderate permeable substance that could penetrate the BBB.

Conclusion We presented preliminary evidence that the MDHB derivative, NO.2, could penetrate the BBB. This indicates that NO.2 has the potential to treat CNS diseases.


Keywords


Methyl 3, 4-dihydroxybenzoate; structural derivatives; blood-brain barrier; central nervous system.

Full Text:

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