Objective: The objective of the present study is focused on the design and synthesis of 16-pyridyl methylene derivatives of steroidal oximes and further their pharmacological evaluation as antiparkinsonian agents in MPTP-injected mice with locomotive impairments which helps to understand the neuroinflammatory mechanism behind the disease and also provide a novel therapeutic regime for Parkinson’s disease.

Background: Parkinson’s disease (PD) is a progressive movement disorder which affects the nervous system of the body and is characterized by a low level of dopamine within the brain which is responsible for both motor and nonmotor dysfunctions. The exact mechanism of underlying disease is still unknown but the implications resulted from the combination of genetic and environmental factors. Various literature reports mentioned that chronic neuroinflammation is one of the major causes of the death of dopaminergic neurons which promotes the implications of PD.

Method: A mixture of DHEA, the appropriate aldehyde and potassium hydroxide in methanol was stirred at room temperature for 2 h to prepare Aldol products which were further refluxed with aqueous solutions of hydroxylamine hydrochloride and sodium acetate trihydrate in aldehyde free alcohol for 6 h. On completion, the solvent was removed and the precipitates were crystallized from methanol to get 16-pyridylmethylene substituted steroidal oximes.  Male laca mice were injected with MPTP (20 mg/kg, i.p.) for 7 days to trigger the neuroinflammation along with a daily dose of 5mg/kg (i.p.) of the synthesized compounds. On the 8^th day, behavioural alternations for locomotive and cognitive dysfunctions were evaluated using the actophotometer, rotarod and elevated plus maze. Biochemical and histopathological estimations have been also carried out. In silico studies were also performed to understand mechanistic insights into underlying disease.

Results: The synthesized derivatives were characterized using IR, ¹H NMR, ¹³C NMR and MS. All the compounds displayed antiparkinsonian activity comparable to that of standard drugs dexamethasone and selegiline.

Conclusion: The present study suggested that 16-(4-pyridylmethylene)-17-oximino-5-androsten-3β-ol acts as the most active compound. Hence, it could be useful for the prevention of chronic neuroinflammation and further for the treatment of Parkinson’s disease.

References: [1] Singh, R., Bansal, R., 2017. Investigations on 16-arylideno steroids as a new class of neuroprotective agents for the treatment of Alzheimer’s and Parkinson’s diseases. ACS Chem. Neurosci. 8, 186–200.

[2] Abdalla, M.M., et al., 2012. A new investigation for some steroidal derivatives as anti- Alzheimer agents. Int. J. Biol. Macromol. 51, 56–63.

[3]Singh R, Bansal R. 2021. 16-Substituted steroids alleviate LPS-induced neurodegenerative disorders in rats. Eur J Pharmacol. 895,173876.

« Back to 2024 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/design-synthesis-and-pharmacological-evaluation-of-16-pyridylmethylene-derivatives-of-steroidal-oximes-as-antiparkinsonian-agents-in-mptp-injected-mice/