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ARS Home » Southeast Area » Oxford, Mississippi » Natural Products Utilization Research » Research » Publications at this Location » Publication #387552
Research Project: Biobased Pesticide Discovery and Product Optimization and Enhancement from Medicinal and Aromatic Crops

Location: Natural Products Utilization Research

Title: Discovery 5a-pregnan-2ß,3a-diol-20-one as a neuroHIV protective agent

Author
item KHAN, MD IMDADUL - University Of Mississippi
item SALAHUDDIN, MOHAMMED - University Of Mississippi
item ALKINS, NICHOLAS - University Of Mississippi
item FAKHRI, MAHDI - University Of Mississippi
item Kim, Seong
item LI, JING - University Of Mississippi
item PARIS, JASON - University Of Mississippi
item LE, HOANG - University Of Mississippi

Submitted to: American Chemical Society
Publication Type: Abstract Only
Publication Acceptance Date: 8/18/2021
Publication Date: N/A
Citation: N/A

Interpretive Summary: The human immunodeficiency virus (HIV) is associated with neuroendocrine dysfunction, contributing to co-morbid stress-sensitive disorders. Multiple mechanisms appear to contribute to neuronal stress and injury underlying HIV-associated neurocognitive disorders (HAND), and Pregnane steroids, particularly allopregnanolone (AlloP), are neuroprotective in response to significant insults. This research emphasized that newly designed compounds that modified stereospecific functionalization will ameliorate the viremia, inflammation, and neurotoxicity caused by infectious HIV-1 in vitro and in vivo. In addition, a library of potential compounds will have a good PK profile, complement cART, and is potent against neuroHIV symptomatology.

Technical Abstract: There has emerged a need for an antiviral with improved delivery to the CNS with the increasing incidence of HIV and HIV-associated neurocognitive disorders. Multiple mechanisms appear to contribute to neuronal stress and injury underlying HIV-associated neurocognitive disorders (HAND), which occur despite the successful introduction of combination antiretroviral therapy (cART). Pregnane steroids, particularly allopregnanolone (AlloP), are neuroprotective in response to significant insults. This research focused on the analogs through stereospecific functionalization at the C2 position of allopregnanolone using a structure-based drug discovery approach. The designed compounds will ameliorate the viremia, inflammation, and neurotoxicity caused by infectious HIV-1 in vitro and in vivo. Preliminary in vitro results of stereospecific functionalized allopregnanolone analogs showed crucial activity, including trans diol installed allopregnanolone analog.