Singh_2018_ACS.Chem.Neurosci_9_272

Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common forms of neurodegenerative disorders. Dehydroepiandrosterone (DHEA) has been reported as a neuroprotective steroid useful in the therapeutic management of neurodegenerative disorders such as AD and PD. Herein we report the synthesis and evaluation of a new series of 16,17-pyrazolinyl DHEA analogues 2-4a-d as neuroprotective agents using LPS-induced neuroinflammation animal models. Treatment with the pyrazoline substituted steroids considerably improved the LPS-induced learning, memory and movement deficits in animal models. Suppression of biochemical parameters of oxidative and nitrosative stress, acetylcholinesterase activity, and TNF-alpha levels was also observed. 16,17-Pyrazolinyl steroids 2c-4c substituted with a 4-pyridyl moiety at the 5-position of the heterocyclic ring were found to be the most potent agents and produced neuroprotective effects better than standard drugs celecoxib and dexamethasone. Of these pyrazoline substituted steroids, the N-acetyl analogue 3c displayed neuroprotective effects better than N-phenyl (4c), which in turn showed potency more than N-unsubstituted analogue 2c.