Studies on 16,17-Pyrazoline Substituted Heterosteroids as Anti-Alzheimer and Anti-Parkinsonian Agents Using LPS Induced Neuroinflammation Models of Mice and Rats

Abstract

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-α 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.

Crystal and Molecular Structure and DFT Calculations of the Steroidal Oxime 6E-Hydroximino-androst-4-ene-3,17-dione (C19H25NO3) a Molecule with Antiproliferative Activity

“…In another area of therapeutic interest, two recent studies involving biomedical-steroid function, promise to lead to interesting structure function studies. It was shown that 16,17-pyrazoline substituted heterosteroids [21] and 16-arylideno steroids [22] both represent a new class of neuroprotective agents for the treatment of Alzheimer's and Parkinson's diseases. In particular it was shown that the introduction of a pyrazoline ring at the 16,17 position of the steroid skeleton resulted in improvement of neuroprotective effects.…”

Novel d-Annulated Pentacyclic Steroids: Regioselective Synthesis and Biological Evaluation in Breast Cancer Cells

“…It should be noted that some of these compounds exhibit no significant hormonal activity [28][29][30][31]. Both heterocyclic analogs I [32][33][34][35][36][37][38][39] and carbocyclic analogs II [40,41] of pentacyclic steroids have attracted considerable attention (Scheme 1). Steroids bearing an additional carbocycle annulated at the 16 and 17 positions of the ring D (III) are characterized by unique biological activity [42][43][44][45].…”

“…It should be noted that some of these compounds exhibit no significant hormonal activity [ 28 , 29 , 30 , 31 ]. Both heterocyclic analogs I [ 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ] and carbocyclic analogs II [ 40 , 41 ] of pentacyclic steroids have attracted considerable attention ( Scheme 1 ).…”

Microwave-Assisted Stereoselective Heterocyclization to Novel Ring d-fused Arylpyrazolines in the Estrone Series

“…In recent years growing interest has been focused on steroidal 2-pyrazolines and pyrazoles due to their antiandrogenic [18] or direct antiproliferative effect [19,20,21] or their ability to inhibit one of the key regulatory enzymes of steroid biosynthesis [22,23,24,25], which makes them potential candidates for the chemoprevention or treatment of cancerous diseases. Some further derivatives are also known to possess neuroprotective [26], antimicrobial [27] or insecticidal activity [28] (Figure 1).…”