Objective: The present study is aimed at design and synthesis of new therapeutically useful steroidal neuroprotective derivatives as anti-parkinsonian agents. The new 16-aryldieno steroidal derivatives have been synthesized by fusing pyridyl moiety at 16 position of the steroid. These D ring modified heterosteroids were then explored for their neuroprotective effects against PD.

Background: Parkinson’s disease (PD) is a long-term degenerative disorder of the central nervous system mainly effecting the motor system and characterized by symptoms such as tremors, bradykinesia, rigidity, postural instability and cognitive deficits. Neuroinflammation play a key role in the pathogenesis of PD.

Methods: Aldol condensation of dehydroepiandrosterone with requisite pyridine carboxaldehyde in basic medium gave corresponding 16-arylidene steroidal derivatives 1a-c. Rats (male wistar) were anesthetized with thiopental sodium (45 mg/kg, i.p.), stereotaxic surgery has been done and intranigral injection of LPS (10µg in 2µl) was infused into left substantia nigra using the Hamilton microsyringe.³ Heterosteroids were evaluated against behavioral alternations using actophotometer, elevated plus maze at dose 2mg/kg after 7^th, 14^th and 21^st day of LPS administration. Biochemical estimation of different makers for neuroinflammation, cholinergic activity and oxidative stress has also been carried out.

Results: The newly synthesized compounds were characterized by elemental and spectral analyses (IR, ¹H NMR). The synthesized heterosteroids 1a-c exhibited potent neuroprotective activity against PD. The pyridin-4-yl group substituted steroid 1c displayed activity comparable to that of standards dexamethasone and celecoxib.

Conclusions: This study suggests that 16-aryldieno steroids exhibit potent neuroprotective activity and they could be useful for the prevention of PD.

References: Kurkowska-Jastrzebska, I.; Litwin, T.; Joniec, I.; Ciesielska, A.; Przybylkowski, A.; Czlonkowski, A.; Czlonkowska, A., Dexamethasone protects against dopaminergic neurons damage in a mouse model of Parkinson’s disease. Int Immunopharmacol 2004, 4 (10-11), 1307-18. Jiang, C. S.; Guo, X. J.; Gong, J. X.; Zhu, T. T.; Zhang, H. Y.; Guo, Y. W., Synthesis and biological evaluation of 21-arylidenepregnenolone derivatives as neuroprotective agents. Bioorg Med Chem Lett 2012, 22 (6), 2226-9.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/synthesis-and-pharmacological-evaluation-of-16-aryldieno-steroids-as-anti-parkinsonian-agents-in-lps-induced-neuroinflammation-model-of-rat/